30-day morbidity and mortality after transoral robotic surgery for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma: A retrospective analysis of two prospective adjuvant de-escalation trials (MC1273 & MC1675).

OBJECTIVE: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials. MATERIALS AND METHODS: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement. RESULTS: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage. CONCLUSION AND RELEVANCE: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.

Characterisation of thymol effects on RDL receptors from the bee parasite Varroa destructor.

A major contributor to bee colony decline is infestation with its most devastating pest, the mite Varroa destructor. To control these mites, thymol is often used, although how it achieves this is not understood. One well-documented action of thymol is to modulate GABA-activated ion channels, which includes insect RDL receptors, a known insecticidal target. Here we have cloned two Varroa RDL subunits, one of which is similar to the canonical RDL subunit, while the other has some differences in M4, and, to a lesser extent, M2 and its binding site loops. Expression of this unusual RDL receptor in Xenopus oocytes reveals GABA-activated receptors, with an EC50 of 56 µM. In contrast to canonical RDL receptors, thymol does not enhance GABA-elicited responses in this receptor, and concentration response curves reveal a decrease in GABA Imax in its presence; this decrease is not seen when similar data are obtained from Apis RDL receptors. We conclude that an M2 T6'M substitution is primarily responsible for the different thymol effects, and suggest that understanding how and where thymol acts could assist in the design of novel bee-friendly miticides.

Management of dental emergencies amongst Australian general medical practitioners - A case-vignette study.

BACKGROUND: In Australia, because of inequity in dental service accessibility and affordability, patients can see general medical practitioners (GPs) for acute dental conditions. METHODS: This cross-sectional study consisted of surveys distributed to the board registered GPs practising in Australia. The main outcome measures included statistical analysis of GPs managing different dental emergency scenarios and their confidence and expectations in managing dental emergencies. RESULTS: A total of 425 GPs participated in the study. The sample primarily consisted of GPs practising in metropolitan clinics (n = 315). Most participants reported that they would refer to the dentist for mobilized tooth (n = 402). There was a negative correlation between GPs with 5-29 years of experience and traumatized tooth management (P < 0.05). GPs aged between 40 and 49 years were more inclined to treat patients with mobilized teeth [Multivariate (MV): 0.42(0.09-0.74)]. However, GPs with 0-5 years of experience were less likely to manage patients with dental abscess [MV: -0.52(-0.80 to -0.24)]. CONCLUSION: Most GPs referred dental emergencies to dentists. GP management of dental emergencies were predominantly palliative. Therefore, opportunities for collaborative practice models amongst GPs and dentists may be needed to bridge the gap in the regional and remote locations.

Impact of feeding n-3 fatty acids to layer breeders and their offspring on concentration of antibody titres against infectious bronchitis, and Newcastle diseases and plasma fatty acids in the offspring.

1. The impact of feeding sources of n-3 fatty acids (FA) to ISA Brown and Shaver White breeders and their offspring on antibody titres and plasma FA profile was examined.2. Breeders were fed either a control diet (CON); CON + 1% microalgae (DMA: Aurantiochytrium limacinum) as a source of docosahexaenoic acid; or CON + 2.6% of a co-extruded mixture of full-fat flaxseed (FFF) as a source of α-linolenic acid. Day-old female offspring were assigned to diets (breeder-offspring): 1) CON-CON, 2) CON-DMA, 3) CON - FFF, 4) DMA - CON, 5) DMA - DMA, 6) FFF - CON or 7) FFF - FFF, followed by a standard layer diet through 18 weeks of age (WOA) to 42 WOA.3. Antibody titres against infectious bronchitis (IBV) and Newcastle disease (NDV) were measured at six days and six WOA, and plasma FA profile was measured at 18 and 42 WOA.4. Pullets from FFF-fed breeders had higher antibody titres against IBV and NDV than pullets fed DMA (P < 0.05). Feeding FFF to offspring increased plasma ∑n-3 FA at 18 and 42 WOA, whereas feeding DMA to offspring reduced ∑n-6 FA at 18 WOA.5. In conclusion, independent of breeder strain, alpha linoleic acid (ALA) and DHA sources showed varied responses. Feeding breeders FFF increased plasma concentration of antibody titres and n-3 FA whereas DMA reduced plasma concentration of ∑n-6 FA.

Secondary non-invasive prenatal screening for fetal trisomy: an effectiveness study in a public health setting.

OBJECTIVE: To evaluate the effectiveness of secondary screening using non-invasive prenatal testing (NIPT) in a routine NHS setting including test performance, turn-around times (TATs) and no-call (failure to obtain result) rates. To examine the influence of maternal and fetal characteristics on test performance. DESIGN: Retrospective cohort. SETTING: London teaching hospital. SAMPLE: A total of 8651 pregnancies undergoing screening for fetal trisomy using NIPT provided by an NHS cell-free DNA screening laboratory - the SAFE laboratory. METHODS: Screening test evaluation and TATs. Univariate and multivariate logistic regression analysis to identify significant predictors of no-call results and reported by low fetal fraction (<2%), very high fetal fraction (>40%) and processing failure. MAIN OUTCOME MEASURES: Test performance, TATs and no-call rates, factors affecting no-call results. RESULTS: Average TAT was 4.0 days (95% CI 4.0-4.2 days). Test sensitivities for trisomies 21 and 13/18 were 98.9% (95% CI 95.9-99.9%) and 90.4% (95% CI 80.0-96.8%), respectively. The overall no-call rate was 32/8651 (0.37%, 95% CI 0.26-0.52%). The overall risk of a no-call result was influenced by gestational age, dichorionic twin pregnancy, history of malignancy and pregnancies affected by trisomy 13/18, but not by maternal weight or use of low-molecular-weight heparin. CONCLUSIONS: High-throughput NIPT can be effectively embedded into a public health NHS setting. TATs of 4 days and no-calls of <0.5% were well within clinically desirable tolerances. Gestational age, maternal weight, assisted reproductive techniques, use of low-molecular-weight heparin and past history of malignancy did not have major impacts on test no-call rates and should not constitute reasons for withholding the option of NIPT from women. TWEETABLE ABSTRACT: Turn-around times of 4 days, no-call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS.

n-3 fatty acids fed to ISA brown and Shaver white breeders and their female progeny during rearing: Impact on egg production, eggshell, and select bone attributes from 18 to 42 weeks of age.

The impact of feeding sources of n-3 fatty acids (FA) to ISA brown and Shaver white breeders and their female offspring during rearing on egg production, eggshell, tibia, and keel bone attributes was examined. Breeders were fed Control (CON) or CON + 1% dried microalgae (DMA: Aurantiochytrium limacinum) as the source of docosahexaenoic acid or CON + 2.6% of a coextruded mixture of full-fat flaxseed (FFF) and pulses as a source of α-linolenic acid. Day-old offspring were fed 1) breeder CON-pullet CON (CON-CON), 2) breeder CON-pullet DMA (CON-DMA), 3) breeder CON-pullet FFF (CON-FFF), 4) breeder DMA-pullet CON (DMA-CON), 5) breeder DMA-pullet DMA (DMA-DMA), 6) breeder FFF-pullet CON (FFF-CON), and 7) breeder FFF-pullet FFF (FFF-FFF). At 18 wk of age (WOA), pullets were fed a common layer diet to 42 WOA for egg production and bone quality assessments. There was no (P > 0.05) interaction between strains and diets and the main effect of diets on egg production, egg mass, and eggshell quality. There was an interaction (P = 0.008) between strain and diet on egg weight (EW); however, the strain effect on EW (P < 0.001) was such that ISA brown had heavier eggs than Shaver white. Shaver white had higher (P < 0.001) eggshell %, eggshell, and tibia breaking strength (BS), as well as tibia ash concentration compared with ISA brown hens. In contrast, ISA brown hens exhibited heavier (P < 0.05) tibia and keel bones. Feeding breeders DMA and pullets both sources of n-3 FA increased tibia medullary ash concentration compared with other diets (P < 0.001). Shaver white hens showed greater decline in tibia BS (83.7 vs. 96.3%) and ash content (84.1 vs. 94.3%) than ISA brown hens from 18 to 42 WOA (P < 0.05). Strain and diets exhibited independent effects on eggshell, tibia, and keel attributes. Provision of α-linolenic acid and docosahexaenoic acid to breeders and offspring improved tibia medullary ash concentration at 42 WOA.

Is it safe for extended-role radiographers to measure migration percentage in children with cerebral palsy?

INTRODUCTION: In the surveillance of children with cerebral palsy, the measurement of migration percentage is used to identify children at risk of hip dislocation. Early identification of children at risk facilitates early intervention with less invasive surgical procedures to prevent further deterioration. The aim of this study is to evaluate the safety of the measurements of migration percentage for surveillance in cerebral palsy by extended-role radiographers by evaluating the reliability and validity of measurements performed by these professionals. METHODS: A sample of thirty pelvic x-rays were selected from the local cerebral palsy database. A range of hip displacement was selected including some challenging borderline x-rays. All ten extended-role radiographers completed measurements using TraumaCAD which were repeated at a minimum of 4 weeks. Inter-rater and intra-rater reliability was calculated using intraclass correlation coefficients. The accuracy and safety of the system was evaluated by converting measurements into referral categories (red, amber or green) and cohen's kappa was calculated when categories were compared to measurements to orthopaedic surgeon RESULTS: The inter-rater reliability between radiographers was 0.938 (95% CI 0.914-0.991). The intra-rater reliability was 0.941 (95% CI 0.931-0.949). The percentage agreement was 94.8% for green, 93.8% for amber and 98.2% for red hips. The weighted kappa value was 0.923 (95% CI 0.889-0.957). CONCLUSION: The reliability and accuracy of radiographer measurement of migration percentage is excellent. It is safe for radiographers to calculate the migration percentage using semi-automated software for the surveillance of children with cerebral palsy. IMPLICATIONS FOR PRACTICE: We recommend the measurement of migration percentage may be performed by extended-role radiographers to deliver accurate and reliable measurements for use in cerebral palsy surveillance.

Impact of feeding microalgae (Aurantiochytrium limacinum) and co-extruded mixture of full-fat flaxseed as sources of n-3 fatty acids to ISA brown and Shaver white breeders and progeny on pullet skeletal attributes at hatch through to 18 weeks of age.

Impact of feeding n-3 fatty acids (FA) to ISA brown and Shaver white breeders and their progeny on bone development in pullets was investigated. Breeders were fed Control (CON); CON + 1% microalgae (DMA: Aurantiochytrium limacinum) as the source of docosahexaenoic acid; and CON + 2.6% of a co-extruded mixture of full-fat flaxseed (FFF) and pulses mixture as source of α-linolenic acid. Test diets (DMA and FFF) were balanced for total n-3 FA and n-6: n-3 FA ratio. Samples of day-old progeny were euthanized for bone mineral content (BMC) and tibia collagen type II. The remaining pullets were fed posthatch treatments as follows: from breeder CON: CON (CON-CON), DMA (CON-DMA), and FFF (CON-FFF), from breeder DMA: CON (DMA-CON) and DMA (DMA-DMA) and from breeder FFF: CON (FFF-CON) and FFF (FFF-FFF). A total of 60 pullets per posthatch diets were reared in cages (12 pullets/cage, n = 5) with free access to feed and water, bled at 6, 12, and 18 wk of age (WOA) for bone turnover markers and necropsied at 18 WOA for tibia and femur samples. Day-old pullets from breeder fed CON had greater BMC (P < 0.001) relative to those from breeders fed other diets. There was strain and diet interaction (P ≤ 0.024) on tibia breaking strength (TBS) and tibia cortical ash concentration at 18 WOA such that diet responses were only observed in Shaver white pullets. In this context, TBS of DMA-DMA and FFF-FFF was greater than for pullets originating from CON breeder, and the cortical ash weight of DMA-DMA and FFF-FFF pullets was 23.8 and 20.2%, respectively, higher than for CON-CON pullets. In conclusions, the strain effects were strong on tibia attributes on 18-week-old pullets. Breeder feeding of n-3 FA was more effective when concomitant with posthatch feeding of n-3 FA in supporting the skeletal strength and cortical bone development in Shaver white pullets. Further investigations are warranted to establish the impact these strategies on skeletal health during laying cycle.

Recent advances in hidradenitis suppurativa in pediatrics.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can cause significant physical, mental, and socioeconomic burden. There remains a paucity of literature on HS in the pediatric population. This systematic review highlights recent advances in pediatric HS in epidemiology, presentation, comorbidities, and management. PubMed, Embase, Google Scholar, and Clinicaltrials.gov databases were used to identify trials and articles published on HS in pediatric patients between January 2015 and October 2019. A total of 39 articles were included. Current evidence suggests that pediatric onset HS may be associated with genetic factors along with endocrine and metabolic abnormalities. Delayed diagnosis in children with HS contributes to poor outcomes. Overall, children and adults with HS share similar lesion types and involved areas. Pediatric HS is associated with a number of comorbid conditions including acne, obesity, inflammatory joint disease, Down syndrome, inflammatory bowel disease, and diabetes. There are currently no pediatric treatment guidelines. Adalimumab is approved for the treatment of moderate-to-severe HS in children 12 and older. Other targeted immunomodulators and hormonal modulators are under investigation. Although the number of studies concerning HS are increasing, further investigation is warranted to better characterize HS, facilitate early diagnosis, and determine the best management for children.

Autonomous Robotic Intracardiac Catheter Navigation Using Haptic Vision.

While all minimally invasive procedures involve navigating from a small incision in the skin to the site of the intervention, it has not been previously demonstrated how this can be done autonomously. To show that autonomous navigation is possible, we investigated it in the hardest place to do it - inside the beating heart. We created a robotic catheter that can navigate through the blood-filled heart using wall-following algorithms inspired by positively thigmotactic animals. The catheter employs haptic vision, a hybrid sense using imaging for both touch-based surface identification and force sensing, to accomplish wall following inside the blood-filled heart. Through in vivo animal experiments, we demonstrate that the performance of an autonomously-controlled robotic catheter rivals that of an experienced clinician. Autonomous navigation is a fundamental capability on which more sophisticated levels of autonomy can be built, e.g., to perform a procedure. Similar to the role of automation in fighter aircraft, such capabilities can free the clinician to focus on the most critical aspects of the procedure while providing precise and repeatable tool motions independent of operator experience and fatigue.

Value of the 'clicky hip' in selective screening for developmental dysplasia of the hip.

AIMS: The aim of this study was to review the value of accepting referrals for children with 'clicky hips' in a selective screening programme for hip dysplasia. PATIENTS AND METHODS: A single-centre prospective database of all referrals to the hip clinic was examined to identify indication for referrals, diagnosis, and treatment. All patients referred received a standardized ultrasound scan and clinical examination by an orthopaedic consultant. RESULTS: There were 5716 children referred to the orthopaedic hip clinic between 1 June 2014 and 26 September 2018. In all, 1754 children (30.1%) were referred due to 'clicky hip' with no additional risk factors or indications for ultrasound scan. A total of 123 children (7.1%) referred with 'clicky hip' and no additional risk factors or examination findings had an abnormal initial hip ultrasound, including 16 children (0.9%) with dysplastic hips. Of the 141 children who required treatment in a Pavlik harness during the study period, 23 (16%) had been referred with a 'clicky hip' and no additional risk factors or examination findings, including six children with Graf 3 or 4 hips. CONCLUSION: There is significant value in reviewing children with an isolated 'clicky hip'. Many children who require treatment are referred to the orthopaedic service as 'clicky hip' with no additional risk factors. In a pragmatic pathway with a diverse population of clinicians performing baby checks, 'clicky hip' is an important indication for referral and should not be discarded. Cite this article: Bone Joint J 2019;101-B:635-638.

Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection.

The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004). The anti-CD154 dAb effectively blocked CD40-CD154 interactions but lacked crystallizable fragment (Fc) binding activity and resultant platelet activation. In a nonhuman primate kidney transplant model, anti-CD154 dAb was safe and efficacious, significantly prolonging allograft survival without evidence of thromboembolism (Median survival time 103 days). The combination of anti-CD154 dAb and conventional immunosuppression synergized to effectively control allograft rejection (Median survival time 397 days). Furthermore, anti-CD154 dAb treatment increased the frequency of CD4+ CD25+ Foxp3+ regulatory T cells. This study demonstrates that the use of a novel anti-CD154 dAb that lacks Fc binding activity is safe without evidence of thromboembolism and is equally as potent as previous anti-CD154 agents at prolonging renal allograft survival in a nonhuman primate preclinical model.

Feeling angry about current health status: using a population survey to determine the association with demographic, health and social factors.

BACKGROUND: Feeling angry about their health status may influence disease progression in individuals, creating a greater burden on the health care system. Identifying associations between different variables and feeling angry about health status may assist health professionals to improve health outcomes. This study used path analysis to explore findings from a population-based survey, informed by qualitative descriptions obtained from focus groups, to determine the prevalence of health-related anger within the community and variables associated with reporting health-related anger. METHODS: A population-based Computer Assisted Telephone Interview (CATI) survey of 3003 randomly selected adults Australia-wide was conducted to examine the prevalence of health-related anger. A wide range of other covariates were included in the survey. Multivariable logistic regression and path analysis were undertaken to identify the relationships between different variables associated with feeling angry about the health status of people, to explore the direction of these associations and as a consequence of the results, consider implications for health service use and delivery. RESULTS: Overall, 18.5 % of the population reported feeling angry about their health "some of the time", "most of the time" or "all of the time". People who felt angry about their health were more likely to have a severe health condition, at least one chronic condition, high psychological distress, fair to poor health status, and needed to adjust their daily lives because of a health condition. Having a tertiary level education was protective. Receiving some form of social support, usually from a support group, and not always doing as advised by a doctor, were also associated with a higher likelihood of being angry about their health. CONCLUSIONS: People living with significant health problems are more likely to feel angry about their health. The path between illness and anger is, however, complex. Further research is needed to understand the extent that feeling angry influences the progression of health problems and, if necessary, how to minimise this progression. What also needs examining is whether identifying people who feel angry in the general population could be a predictor of persons most likely to develop significant health problems.

Manipulation and reduction of paediatric fractures of the distal radius and forearm using intranasal diamorphine and 50% oxygen and nitrous oxide in the emergency department: a 2.5-year study.

UNLABELLED: A retrospective study was performed in 100 children aged between two and 16 years, with a dorsally angulated stable fracture of the distal radius or forearm, who were treated with manipulation in the emergency department (ED) using intranasal diamorphine and 50% oxygen and nitrous oxide. Pre- and post-manipulation radiographs, the final radiographs and the clinical notes were reviewed. A successful reduction was achieved in 90 fractures (90%) and only three children (3%) required remanipulation and Kirschner wire fixation or internal fixation. The use of Entonox and intranasal diamorphine is safe and effective for the closed reduction of a stable paediatric fracture of the distal radius and forearm in the ED. By facilitating discharge on the same day, there is a substantial cost benefit to families and the NHS and we recommend this method. TAKE HOME MESSAGE: Simple easily reducible fractures of the distal radius and forearm in children can be successfully and safely treated in the ED using this approach, thus avoiding theatre admission and costly hospital stay.

Effectiveness of the Kids in Control of Food (KICk-OFF) structured education course for 11-16 year olds with Type 1 diabetes.

AIM: To assess the effect of a 5-day structured education course (Kids in Control of Food; KICk-OFF) on biomedical and psychological outcomes in young people with Type 1 diabetes. METHODS: This was a cluster-randomized trial involving 31 UK paediatric centres. Participants were recruited prior to stratified centre randomization. Intervention centres delivered KICk-OFF courses, whereas control centres delivered usual care. Participants were 11-16 years of age and had Type 1 diabetes for at least one year. The KICk-OFF course was delivered by trained educators to eight participants per course. Glycaemic control and quality of life were measured at baseline, 6, 12 and 24 months. Secondary outcomes were hypoglycaemia, ketoacidosis, fear of hypoglycaemia and diabetes self-efficacy. RESULTS: Three hundred and ninety-six participants provided baseline data (199 intervention and 197 control). At 6 and 12 months the intervention group showed significantly improved total generic quality of life scores compared with controls (baseline: 80 vs. 82; 6 months: 82 vs. 82; P = 0.04). Across the whole intervention group mean HbA1c levels were not significantly different from controls; baseline HbA1c mean (95% confidence interval), 78 mmol/mol (75-81) vs. 76 mmol/mol (74-79) [9.3% (9-9.6%) vs. 9.1% (8.9-9.4%); 24 months: 77 mmol/mol (74-79) vs. 78 mmol/mol (75-81) (9.2% (8.9-9.4%) vs. 9.3% (9-9.6%)], adjusted mean difference, -2.0 mmol/mol (6.5-2.5) [2.3% (-2.7% to 2.4%)], P = 0.38. CONCLUSIONS: Attending a KICk-OFF course was associated with significantly improved total quality of life scores within 6 months. Glycaemic control, as measured by HbA1c , was no different at 24 months. (Clinical Trial Registry No: ISRCTN3704268).

Antigen-specific cytotoxic T lymphocytes target airway CD103+ and CD11b+ dendritic cells to suppress allergic inflammation.

Allergic airway inflammation is driven by the recognition of inhaled allergen by T helper type 2 (Th2) cells in the airway and lung. Allergen-specific cytotoxic T lymphocytes (CTLs) can strongly reduce airway inflammation, however, the mechanism of their inhibitory activity is not fully defined. We used mouse models to show that allergen-specific CTLs reduced early cytokine production by Th2 cells in lung, and their subsequent accumulation and production of interleukin (IL)-4 and IL-13. In addition, treatment with specific CTLs also increased the proportion of caspase(+) dendritic cells (DCs) in mediastinal lymph node (MLN), and decreased the numbers of CD103(+) and CD11b(+) DCs in the lung. This decrease required expression of the cytotoxic mediator perforin in CTLs and of the appropriate MHC-antigen ligand on DCs, suggesting that direct CTL-DC contact was necessary. Lastly, lung imaging experiments revealed that in airway-challenged mice XCR1-GFP(+) DCs, corresponding to the CD103(+) DC subset, and XCR1-GFP(-) CD11c(+) cells, which include CD11b(+) DCs and alveolar macrophages, both clustered in the areas surrounding the small airways and were closely associated with allergen-specific CTLs. Thus, allergen-specific CTLs reduce allergic airway inflammation by depleting CD103(+) and CD11b(+) DC populations in the lung, and may constitute a mechanism through which allergic immune responses are regulated.

Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial.

BACKGROUND: We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial. PATIENTS AND METHODS: The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or letrozole) included 4922 women, of whom 4091 had central pathology review. Histotype groups were defined as: mucinous (N = 100), tubular/cribriform (N = 83), ductal (N = 3257), and other (N = 651). Of 183 women with either mucinous or tubular/cribriform tumors, 96 were randomly assigned to letrozole and 87 to tamoxifen. Outcomes assessed were disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Median follow-up in the analytic cohort was 8.1 years. RESULTS: Women with tubular/cribriform breast cancer had the best outcomes for all end points compared with the other three histotypes, and had less breast cancer recurrence (97.5% 5-year BCFI) than those with mucinous (93.5%), ductal (88.9%), or other (89.9%) histotypes. Patients with mucinous or tubular/cribriform carcinoma had better DRFI (5-year rates 97.8% and 98.8%, respectively) than those with ductal (90.9%) or other (92.1%) carcinomas. Within the subgroup of women with special histotypes, we observed a nonsignificant increase in the hazard of breast cancer recurrence with letrozole [hazard (letrozole versus tamoxifen): 3.31, 95% confidence interval 0.94-11.7; P = 0.06]. CONCLUSIONS: Women with mucinous or tubular/cribriform breast cancer have better outcomes than those with other histotypes, although the observation is based on a limited number of events. In postmenopausal women with these histotypes, the magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with mucinous or tubular/cribriform disease. CLINICALTRIALSGOV: NCT00004205.

Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.