The Economic Impact of a Pilot Digital Day-Case Pathway for Knee Arthroplasty in a U.K. Setting.

Knee replacements are an increasingly common procedure in the U.K. National Health Service (NHS). Importantly, the pathway for such procedures represents a prime opportunity to leverage digital technology, modernize and streamline the approach to care, and free up resources. Methods: In this 21-patient pilot study, we assessed the impact of implementing a digital day-case pathway for knee replacement surgery at the Calderdale and Huddersfield NHS Foundation trust. Results: Fourteen (67%) of the 21 eligible patients were treated as day cases, with an average length of stay of 8.8 hours. The pilot data were utilized to model the potential impact of implementing a digital day-case program more widely across the trust. This model showed increased efficiency over the entire episode of care, with reductions in physiotherapy appointments, preoperative visits, hospital days, and face-to-face consultations. Not only would these improvements free up capacity, but they would also result in an estimated saving of £240,540 to the trust while reducing the CO2 footprint of knee replacements by 119,381 kg CO2 emitted. A sensitivity analysis revealed that, even with substantial variation of several key variables within the pathway, a trust-wide digital day-case program would still be a cost-saving measure. Conclusions: Overall, the present study supports the growing notion that digital technology can facilitate the transformation of care pathways, resulting in greater efficiency and financial savings for health-care providers while reducing the time patients spend in the hospital. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Exploring the Impact and Acceptance of Wearable Sensor Technology for Pre- and Postoperative Rehabilitation in Knee Replacement Patients: A U.K.-Based Pilot Study.

Knee replacement operations are common, highly successful procedures that are increasing in frequency. The COVID-19 pandemic has emphasized the need for innovative care pathways that reduce face-to-face appointments. We report on the impact of introducing a wearable sensor for pre- and postoperative rehabilitation of 21 knee replacement patients at 2 hospitals in the U.K. Methods: The sensor (BPMpathway; 270 Vision) was provided during joint school prior to knee replacement and stayed with the patient until a maximum of 9 weeks post-surgery. Participant progress and exercise were monitored remotely, with exercise regimens altered as required. Participants and clinicians could communicate remotely via the device. Results: The median range of motion during the first week post-surgery was 63° (interquartile range [IQR] = 21°) and increased to 136° (IQR = 16°) by week 7. The rate of participant compliance with exercises using the device was 32.3% for thrice-daily compliance and 52.4% for once-daily compliance. The 2-way communication channel was well utilized by both participants and clinicians. We report a 35.7% reduction in face-to-face physiotherapy appointments compared with standard practice. Finally, >80% of users who completed the feedback questionnaire reported a positive experience using the device, finding it easy to understand and reporting that it motivated them to perform their exercises. Conclusions: The use of BPMpathway was well received, effective, and reduced face-to-face physiotherapy appointments. Clinical Relevance: Remote monitoring can reduce the burden to the outpatient physiotherapy service by supporting the post-COVID-19 surgical service recovery plans of the National Health Service and allowing patients to recuperate at home.

Distinct tumor-infiltrating lymphocyte landscapes are associated with clinical outcomes in localized non-small-cell lung cancer.

BACKGROUND: Despite the importance of tumor-infiltrating T lymphocytes (TILs) in cancer biology, the relationship between TIL phenotypes and their prognostic relevance for localized non-small-cell lung cancer (NSCLC) has not been well established. PATIENTS AND METHODS: Fresh tumor and normal adjacent tissue was prospectively collected from 150 patients with localized NSCLC. Tissue was comprehensively characterized by high-dimensional flow cytometry of TILs integrated with immunogenomic data from multiplex immunofluorescence, T-cell receptor sequencing, exome sequencing, RNA sequencing, targeted proteomics, and clinicopathologic features. RESULTS: While neither the magnitude of TIL infiltration nor specific TIL subsets were significantly prognostic alone, the integration of high-dimensional flow cytometry data identified two major immunotypes (IM1 and IM2) that were predictive of recurrence-free survival independent of clinical characteristics. IM2 was associated with poor prognosis and characterized by the presence of proliferating TILs expressing cluster of differentiation 103, programmed cell death protein 1, T-cell immunoglobulin and mucin-domain containing protein 3, and inducible T-cell costimulator. Conversely, IM1 was associated with good prognosis and differentiated by an abundance of CD8+ T cells expressing cytolytic enzymes, CD4+ T cells lacking the expression of inhibitory receptors, and increased levels of B-cell infiltrates and tertiary lymphoid structures. While increased B-cell infiltration was associated with good prognosis, the best prognosis was observed in patients with tumors exhibiting high levels of both B cells and T cells. These findings were validated in patient tumors from The Cancer Genome Atlas. CONCLUSIONS: Our study suggests that although the number of infiltrating T cells is not associated with patient survival, the nature of the infiltrating T cells, resolved in distinct TIL immunotypes, is prognostically relevant in NSCLC and may inform therapeutic approaches to clinical care.

Analysis of trimodal and bimodal therapy in a selective-surgery paradigm for locally advanced oesophageal squamous cell carcinoma.

BACKGROUND: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. METHODS: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. RESULTS: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). CONCLUSION: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.

Evaluating the use of gradient echo imaging for the detection of cerebral microbleeds in acute stroke cases: A retrospective data analysis in a UK stroke unit.

INTRODUCTION: Imaging in stroke, allows its classification into ischaemic stroke (IS) or intracranial haemorrhagic stroke (ICH), ensuring time-sensitive treatment to be administered. Imaging can also allow detection of cerebral microbleeds (CMBs), which may further determine pharmacological intervention in acute stroke. True gradient echo (T2∗GRE) or susceptibility weighted imaging (SWI) have high sensitivity for the detection of CMBs. These two sequences are included in the national guidelines; however, the implementation of these guidelines can vary depending on local interpretation and scanner capabilities. AIM: To explore the use and application of blood sensitive MRI sequences in a specialist UK stroke unit for the detection of CMBs, to improve local practice. METHODS: A retrospective data analysis of the native database, spanning a 6-month period, was used. The data of 281 acute stroke patients with an MRI were reviewed and analysed. The MRI sequences applied, and the final diagnosis were noted for each case. RESULTS: Of the 281 acute stroke patients with MRI, 259 (92.1%) had an IS, 16 (5.68%) an ICH and 6 (2.14%) had both. Overall, 13 (4.63%) had a CMB diagnosis. All of these 13 patients had a true T2∗GRE sequence. CMBs were not detected in the absence of a T2∗GRE sequence. CONCLUSION: T2∗GRE imaging is essential for detecting CMBs. When omitted, CMB incidence can be considerably lower than that suggested in the literature. Missing CMB diagnoses in stroke patients may result in suboptimal treatment pathways, compromising the patients' standard of care. IMPLICATIONS FOR PRACTICE: When SWI is not available, it is imperative to always include a true T2∗GRE sequence to detect microbleeds in suspected acute stroke cases.

Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Compact laser system for a laser-cooled ytterbium ion microwave frequency standard.

The development of a transportable microwave frequency standard based on the ground-state transition of 171Yb+ at ∼12.6 GHz requires a compact laser system for cooling the ions, clearing out of long-lived states and also for photoionisation. In this paper, we describe the development of a suitable compact laser system based on a 6U height rack-mounted arrangement with overall dimensions 260 × 194 × 335 mm. Laser outputs at 369 nm (for cooling), 399 nm (photoionisation), 935 nm (repumping), and 760 nm (state clearout) are combined in a fiber arrangement for delivery to our linear ion trap and we demonstrate this system by cooling of 171Yb+ ions. Additionally, we demonstrate that the lasers at 935 nm and 760 nm are close in frequency to water vapor and oxygen absorption lines, respectively; specifically, at 760 nm, we show that one 171Yb+ transition is within the pressure broadened profile of an oxygen line. These molecular transitions form convenient wavelength references for the stabilization of lasers for a 171Yb+ frequency standard.

Identifying hospital-acquired infections using retrospective record review from the Irish National Adverse Events Study (INAES) and European point prevalence survey case definitions.

BACKGROUND: Point prevalence surveys (PPSs) collect data on hospital-acquired infections (HAIs) at one point in time but do not provide information on incidence over the entire admission or impact on patients or healthcare resources. Retrospective record review examines the entire admission to determine adverse event prevalence, incidence, preventability, physical impairment and additional length of stay. AIM: To establish whether European HAI surveillance definitions can be applied to the Irish National Adverse Events Study (INAES) retrospective record review data to determine HAI burden. METHODS: In the INAES, 1574 admissions were reviewed using a two-stage methodology and 247 adverse events were found. These were examined against European HAI case definitions to determine whether the event was an HAI. Results were compared with the 2011/12 European PPS data for Ireland. FINDINGS: The prevalence of HAI adverse events in INAES was 4.4% (95% confidence interval (CI) 3.1-6.1%) with an incidence of 3.8 (95% CI 2.5-5.2) HAI adverse events per 100 admissions. The PPS HAI prevalence for Ireland was 5.2%. HAI types and micro-organisms were similar in INAES and the PPS. Approximately three-quarters of INAES HAI adverse events were preventable, 7% caused permanent impairment and 7% contributed to death. A mean of 10 additional bed days were attributed to HAI adverse events, equivalent to €9400 per event. CONCLUSION: Retrospective record review is an accurate source of information on HAI incidence, preventability and impact that complements PPS prevalence rates. HAI adverse events result in higher costs to the healthcare system than other adverse events.

Comparing enrolees with non-enrolees of cancer-patient navigation at end of life.

Background: Cancer-patient navigators who are oncology nurses support and connect patients to resources throughout the cancer care trajectory, including end of life. Although qualitative and cohort studies of navigated patients have been reported, no population-based studies were found. The present population-based study compared demographic, disease, and outcome characteristics for decedents who had been diagnosed with cancer by whether they did or did not see a navigator. Methods: This retrospective study used patient-based administrative data in Nova Scotia (cancer registry, death certificates, navigation visits) to generate descriptive statistics. The study population included all adults diagnosed with cancer who died during 2011-2014 of a cancer or non-cancer cause of death. Results: Of the 7694 study decedents, 74.9% had died of cancer. Of those individuals, 40% had seen a navigator at some point in their disease trajectory. The comparable percentage for those who did not die of cancer was 11.9%. Decedents at the oldest ages had the lowest navigation rates. Navigation rates, time from diagnosis to death, and time from last navigation visit to death varied by disease site. Conclusions: This population-based study of cancer-patient navigation enrolees compared with non-enrolees is the first of its kind. Most findings were consistent with expectations. However, we do not know whether the rates of navigation are consistent with the navigation needs of the population diagnosed with cancer. Because more people are living longer with cancer and because the population is aging, ongoing surveillance of who requires and who is using navigation services is warranted.

Lessons from aviation - the role of checklists in minimally invasive cardiac surgery.

We describe an adverse event during minimally invasive cardiac surgery that resulted in a multi-disciplinary review of intra-operative errors and the creation of a procedural checklist. This checklist aims to prevent errors of omission and communication failures that result in increased morbidity and mortality. We discuss the application of the aviation - led "threats and errors model" to medical practice and the role of checklists and other strategies aimed at reducing medical errors.

Online patient safety education programme for junior doctors: is it worthwhile?

BACKGROUND: Increasing demand exists for blended approaches to the development of professionalism. Trainees of the Royal College of Physicians of Ireland participated in an online patient safety programme. AIMS: Study aims were: (1) to determine whether the programme improved junior doctors' knowledge, attitudes and skills relating to error reporting, open communication and care for the second victim and (2) to establish whether the methodology facilitated participants' learning. METHODS: 208 junior doctors who completed the programme completed a pre-online questionnaire. Measures were "patient safety knowledge and attitudes", "medical safety climate" and "experience of learning". Sixty-two completed the post-questionnaire, representing a 30 % matched response rate. RESULTS: Participating in the programme resulted in immediate (p < 0.01) improvement in skills such as knowing when and how to complete incident forms and disclosing errors to patients, in self-rated knowledge (p < 0.01) and attitudes towards error reporting (p < 0.01). Sixty-three per cent disagreed that doctors routinely report medical errors and 42 % disagreed that doctors routinely share information about medical errors and what caused them. Participants rated interactive features as the most positive elements of the programme. CONCLUSIONS: An online training programme on medical error improved self-rated knowledge, attitudes and skills in junior doctors and was deemed an effective learning tool. Perceptions of work issues such as a poor culture of error reporting among doctors may prevent improved attitudes being realised in practice. Online patient safety education has a role in practice-based initiatives aimed at developing professionalism and improving safety.

Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab.

BACKGROUND: Trastuzumab has changed the natural history of metastatic HER2 positive breast cancer. Some patients remain well and in remission for many years. There is currently no established duration after which trastuzumab in the advanced setting can be safely discontinued. This study aims to evaluate long-term efficacy and cardiac safety of trastuzumab when used as first-line treatment for patients with metastatic HER2 positive breast cancer. PATIENT AND METHODS: We retrospectively identified 215 patients with HER2 positive, locally advanced or metastatic breast cancer who commenced first line trastuzumab-containing therapy for metastatic disease between 2001 and 2010 at The Royal Marsden Hospital. RESULTS: The median progression free survival for all patients was 12 months (95%CI: 10.3-14.6 months); 103 (48%) patients remained in remission beyond one year, 59 (27%) beyond two years and 25 (12%) beyond five years. The median overall survival was 2.6 years (95% confidence interval (CI): 2.2-3.3). The objective response rate (ORR) was 65% with 17 (8%) complete responses and 120 (57%) partial responses. Trastuzumab was well tolerated. Twenty eight (13%) patients recorded any grade of left ventricular dysfunction. There was no significant difference in cardiac toxicity between those patients on less than or more than one year of trastuzumab. CONCLUSION: Trastuzumab is associated with long-term remissions in a significant proportion of patients with metastatic HER2 positive disease when used in the first-line advanced setting.

Meta-analysis of suicide rates among psychiatric in-patients.

OBJECTIVE: To examine factors associated with the number of psychiatric admissions per in-patient suicide and the suicide rate per 100,000 in-patient years in psychiatric hospitals. METHOD: Random-effects meta-analysis was used to calculate pooled estimates, and meta-regression was used to examine between-sample heterogeneity. RESULTS: Forty-four studies published between 1945 and 2013 reported a total of 7552 in-patient suicides. The pooled estimate of the number of admissions per suicide calculated using 39 studies reporting 150 independent samples was 676 (95% CI: 604-755). Recent studies tended to report higher numbers of admissions per suicide than earlier studies. The pooled estimate of suicide rates per 100,000 in-patient years calculated using 27 studies reporting 95 independent samples was 147 (95% CI: 138-156). Rates of suicide per 100,000 in-patient years tended to be higher in more recent samples, in samples from regions with a higher whole of population suicide rate, in samples from settings with a shorter average length of hospital stay and in studies using coronial records to define suicide. CONCLUSION: Rates of in-patient suicide in psychiatric hospitals vary remarkably and are disturbingly high. Further research might clarify the extent to which patient factors and the characteristics of in-patient facilities contribute to the unacceptable mortality in psychiatric hospitals.

Maternal vitamin D and E intakes during early pregnancy are associated with airway epithelial cell responses in neonates.

BACKGROUND: Antenatal factors including maternal diet may predispose to airway disease, possibly by impacting on fetal airway development. OBJECTIVE: This cohort study tested the hypothesis that maternal vitamin D and E status in early pregnancy is associated with airway epithelial cell (AEC) responses in new born infants and examined constitutive and TNFα/IL-1ß, house dust mite (HDM) extract or lipopolysaccharide (LPS)-stimulated neonatal AEC responses in vitro. METHODS: Maternal dietary vitamin D and E intakes (plasma 25[OH]D3 or α-tocopherol) were characterized at 10-12 weeks gestation. Neonatal nasal AECs were collected soon after birth and cultured to tertiary passage. Constitutive and stimulated - TNFα/IL-1ß, HDM extract or LPS - secretory responses (VEGF, RANTES, MCP-1, IL-17A, IFN-γ, GM-CSF, eotaxin, MIP1-α, MIP1-ß, ICAM, IL-6, IL-8, IL-10, TNF) in 139 AEC cultures were quantified. RESULTS: AEC mediator release was greater following TNF-α/IL-1ß, HDM or LPS stimulation compared to constitutive release. Increased maternal dietary vitamin D was associated with significant increases in IL-10 release by AEC after stimulation with TNF-α/IL-1ß (P = 0.024) or HDM (P = 0.049). Maternal plasma α-tocopherol at 10-12 weeks gestation was positively associated with MIP1α (Spearman's rho 0.242, P = 0.009) and IL-3 (ρ 0.189, P = 0.043) responses after TNF-α/IL-1ß stimulation and negatively associated with TNF (ρ -0.404, P = 0.011) and MIP1ß (ρ -0.322, P = 0.046) responses after LPS stimulation. DISCUSSION: Neonatal AECs respond to pro-inflammatory and allergenic stimuli in vitro demonstrating their potential to function as components of the innate immune response. Our findings suggest that associations exist between maternal micronutrient intake during early pregnancy and aspects of stimulated neonatal airway epithelial cell secretory function that may in turn impact on the development of asthma and/or allergic rhinitis in later life.

The relationship between BNP, NTproBNP and echocardiographic measurements of systemic blood flow in very preterm infants.

OBJECTIVE: Preterm infants are at risk of circulatory compromise following birth. Functional neonatal echocardiography including superior vena cava (SVC) flow is increasingly used in neonatal medicine, and low SVC flow has been associated with adverse outcome. However, echocardiography is not readily available in many neonatal units and B-type natriuretic peptides (BNPs) may be useful in guiding further cardiovascular assessment. This study investigated the relationship between BNP, N-terminal pro-BNP (NTproBNP) and echocardiographic measurements of systemic blood flow in very preterm infants. STUDY DESIGN: This is a prospective observational study. Sixty preterm infants <32 weeks gestational age were included after the treating neonatologist had requested an echocardiogram for suspected cardiovascular compromise. BNP and NTproBNP were sampled just before the echocardiogram. Echocardiographic examination included fractional shortening (FS), SVC flow, left and right ventricular output (LVO and RVO). Statistical analysis included simple linear regression of BNP and NTproBNP with echocardiographic measures and multiple regression including potential confounding variables. RESULT: Mean (s.d.) gestational age at birth was 27(5) (2(1)) weeks, median (interquartile range, IQR) birth weight was 995 (845 to 1175) grams. Neither BNP nor NTproBNP correlated with SVC flow (BNP 95% confidence interval (CI) -0.0014 to 0.013, P=0.12; NTproBNP 95% CI -0.00069 to 0.01, P=0.085); LVO (BNP 95% CI -0.00078 to 0.0072, P=0.11; NTproBNP 95% CI -0.0034 to 0.0034, P=0.99); RVO (BNP 95% CI -0.00066 to 0.0058, P=0.12; NTproBNP 95% CI -0.0012 to 0.0044, P=0.25); or FS (BNP 95% CI -0.053 to 0.051, P=0.96; NTproBNP 95% CI -0.061 to 0.019, P=0.3). Multivariate linear regression did not significantly alter results. CONCLUSION: In this cohort of very preterm infants, BNP and NTproBNP did not correlate with echocardiographic measurements of systemic blood flow within the first 72 h of life.

Photonic-plasmonic-coupled nanoantennas for polarization-controlled multispectral nanofocusing.

We report on the design and experimental demonstration of array-enhanced nanoantennas for polarization-controlled multispectral nanofocusing in the near-IR spectral range. We design plasmonic double bow-tie nanoantennas-coupled to multiple-periodic nanoparticle arrays to harvest radiation of designed wavelengths from a large spatial area and to focus it into a targeted nanoscale region. Near-field calculations were performed on a gold nanoantenna array using three-dimensional finite difference time domain simulations. Cross-shaped optical nanoantennas were fabricated on glass substrates using electron beam lithography. The optical characterization of the fabricated nanoantennas was performed using second harmonic excitation spectroscopy that demonstrates multiwavelength photonic coupling in good agreement with the antenna modeling. The nanoantenna structures introduced in this Letter provide the ability to focus optical energy into deep subwavelength areas and to address multiple spectral regions with polarization control. Such attributes are highly desirable in optical biosensing, enhanced Raman scattering, and for nonlinear plasmonic applications.

Inhibitory effects of Montelukast on mediator release by nasal epithelial cells from asthmatic subjects with or without allergic rhinitis.

AIMS: This study tested inhibitory effects of in vitro Montelukast treatment on nasal airway epithelial cells (AEC) cultured from asthmatic patients treated with Montelukast with and without concomitant allergic rhinitis. We further examined the effect of Montelukast withdrawal in these patients on cytokine release from cultured nasal AEC. METHODS: Nasal AEC were collected by brushings from subjects with a history of stable (no exacerbations or change in medication for ≥ 1 month) physician confirmed mild/moderate asthma whose asthma symptoms were documented to benefit from Montelukast treatment (NCT01230437). Release of the following mediators by nasal AEC were measured: IL-8, IL-6, IL-10, GM-CSF, RANTES, eotaxin and IFN-γ. Nasal AEC were cultured before and one week after withdrawal of their Montelukast treatment. RESULTS: Forty two asthmatics were recruited. Nasal AEC were successfully cultured in 17 at the first assessment, 14 at the second assessment and in 10 individuals at both assessments. Nasal AEC release was no different between asthmatics with or without allergic rhinitis. Montelukast significantly suppressed the release of IL-8 (p = 0.016), IL-6 (p = 0.006), RANTES (p = 0.002) and IFN-γ (p = 0.046), in a dose dependent manner in unstimulated cultures but not in those stimulated with IL-1/TNF. Withdrawal of Montelukast treatment, was associated with increased IL-8 and RANTES secretion in unstimulated nasal AEC cultured from subjects with asthma and allergic rhinitis but not with asthma alone. CONCLUSIONS: Montelukast treatment for asthma symptoms reversibly suppresses nasal AEC release of pro-inflammatory mediators (i.e. IL-8 and RANTES) but only in those cells cultured from subjects with concomitant allergic rhinitis.

A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer.

BACKGROUND: The contribution of induction chemotherapy (IC) before preoperative chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC would increase the rate of pathologic complete response (pathCR). METHODS: Trimodality-eligibile patients were randomized to receive no IC (Arm A) or IC (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted ∼5-6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality, overall survival (OS), and toxic effects were assessed. Bayesian methods and Fisher's exact test were used. RESULTS: One hundred twenty-six patients were randomized dynamically to balance the two arms for histology, baseline stage, gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months [95% confidence interval (CI), 27.63-NA], with median OS 45.62 months (95% CI 25.56-NA) in Arm A and 43.68 months (95% CI 27.63-NA) in Arm B (P = 0.69). The pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided Fisher's exact test, P = 0.094). Safety was similar in both arms. CONCLUSIONS: These data suggest that IC produces non-significant increase in the pathCR rate and does not prolong OS. Further development of IC before chemoradiation may not be beneficial. Clinical trial no.: NCT 00525915 (www.clinicaltrials.gov).

Goserelin with chemotherapy to preserve ovarian function in pre-menopausal women with early breast cancer: menstruation and pregnancy outcomes.

BACKGROUND: Premature ovarian failure and infertility following chemotherapy in early breast cancer (EBC) are major concerns for young women. The role of gonadotrophin-releasing hormone (GnRH) agonists with chemotherapy in EBC in reducing the incidence of chemotherapy-induced early menopause remains uncertain, and long-term data on the recovery of fertility are sparse. We report an audit of our experience with the GnRH agonist, goserelin (Zoladex®), used with chemotherapy to preserve ovarian function and maintain fertility. PATIENTS AND METHODS: Pre-menopausal women were given goserelin subcutaneously every 28 days during chemotherapy, starting 0-14 days before treatment. The main clinical end point was recovery of menstruation after chemotherapy. The other end points were rate of successful conception and median time to recovery of menses. RESULTS: About 84% of 125 women recovered menstruation with the median time to recovery of 6 months (1-43 months), including 76% of 71 patients aged over 35. Of the 42 patients who attempted pregnancy, 71% (n=30) managed to achieve pregnancies. At the time of analysis, there were 42 pregnancies and 30 healthy deliveries. CONCLUSIONS: The GnRH agonist, goserelin, given with chemotherapy for EBC is associated with a low risk of long-term chemotherapy-induced amenorrhoea and a high chance of pregnancy. Further randomised trials are needed.