Iron intake,oxidative stress-related genes and breast cancer risk

Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case–control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER–/PR– breast cancer risk (all p_trend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR_{>18 vs. 0 mg/day} = 0.68, 95% CI: 0.51–0.91), and dietary heme iron was associated with an increased risk, particularly the ER–/PR– subtype (OR_{highest vs. lowest quintile} = 1.69, 95% CI: 1.16–2.47; p_trend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (p_interaction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.     

Overdentures borne on less than four abutments with telescopic crowns: 5-year results of a retrospective clinical study

Clinical Oral Investigations - Retrospective evaluation of the clinical performance of tooth-supported overdentures retained by resilient telescopic crowns with occlusal clearance fit (ODRTC) in...     

Clinical responses with T lymphocytes targeting malignancy-associated κ light chains

BACKGROUND. Treatment of B cell malignancies with adoptive transfer of T cells with a CD19-specific chimeric antigen receptor (CAR) shows remarkable clinical efficacy. However, long-term persistence of T cells targeting CD19, a pan–B cell marker, also depletes normal B cells and causes severe hypogammaglobulinemia. Here, we developed a strategy to target B cell malignancies more selectively by taking advantage of B cell light Ig chain restriction. We generated a CAR that is specific for the κ light chain (κ.CAR) and therefore recognizes κ-restricted cells and spares the normal B cells expressing the nontargeted λ light chain, thus potentially minimizing humoral immunity impairment.METHODS. We conducted a phase 1 clinical trial and treated 16 patients with relapsed or refractory κ⁺ non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) or multiple myeloma (MM) with autologous T cells genetically modified to express κ.CAR (κ.CARTs). Other treatments were discontinued in 11 of the 16 patients at least 4 weeks prior to T cell infusion. Six patients without lymphopenia received 12.5 mg/kg cyclophosphamide 4 days before κ.CART infusion (0.2 × 10⁸ to 2 × 10⁸ κ.CARTs/m²). No other lymphodepletion was used.RESULTS. κ.CART expansion peaked 1–2 weeks after infusion, and cells remained detectable for more than 6 weeks. Of 9 patients with relapsed NHL or CLL, 2 entered complete remission after 2 and 3 infusions of κ.CARTs, and 1 had a partial response. Of 7 patients with MM, 4 had stable disease lasting 2–17 months. No toxicities attributable to κ.CARTs were observed.CONCLUSION. κ.CART infusion is feasible and safe and can lead to complete clinical responses.TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00881920","term_id":"NCT00881920"}}NCT00881920.FUNDING. National Cancer Institute (NCI) grants 3P50CA126752 and 5P30CA125123 and Leukemia and Lymphoma Society (LLS) Specialized Centers of Research (SCOR) grant 7018.     

A retrospective assessment of outcomes of chemotherapy-based versus radiation-only adjuvant treatment for completely resected stage I-IV uterine carcinosarcoma

PurposeTo determine the progression-free survival (PFS) and overall survival (OS) in a cohort of patients who received either platinum-based chemotherapy with or without radiation therapy (pelvic or WAI), or RT alone.MethodsMemorial Sloan-Kettering Cancer Center (MSKCC) electronic medical records from 8/1/1995 to 10/3/2007 were reviewed for patient age, diagnosis date, type of primary surgery, residual disease at the completion of primary surgery, FIGO stage, treatment details, dates of progression and death, and site(s) of first recurrence. PFS and OS by stage (I/II v III/IV) and by treatment type (chemotherapy with or without RT v RT alone) were determined using landmark analyses 8 weeks after surgery. Patients who received chemotherapy with or without RT (pelvic or abdominal) or RT alone (pelvic or abdominal) were included in the analysis. Both groups were allowed to have received intravaginal radiation therapy (IVRT).ResultsForty-nine patients met study criteria. Thirty-eight/49 patients received chemotherapy: 23/38 (60.5%) received paclitaxel-carboplatin; 7/38 (18.4%) received ifosfamide-platinum; 8/38 (21.0%) received other chemotherapy. FIGO stage was: I = 15 (31%); II = 5 (10%); III = 21 (43%); IV = 8 (16%). Three-year PFS for the entire cohort was 24%. Three-year OS for the entire cohort was 60%. Three-year median PFS time for the entire cohort was 15 months (95% CI: 11–25 months). Three-year median OS time for the entire cohort was 67 months (95% CI: 23–89 months). Three-year PFS for stages I–II was 43% v 14% for stages III–IV (HR = 1.98 [0.9–4.33]); P = 0.082. Three-year OS for stages I–II was 68% v 55% for stages III–IV (HR = 1.26 [0.47–3.41]); P = 0.648. Three-year PFS for chemotherapy with or without RT was 35% v 9% for RT alone (HR = 1.74 [0.79–3.85]); P = 0.164. Three-year OS for chemotherapy with or without RT was 66% v 34% for RT alone (HR = 2.02 [0.77–5.33]); P = 0.146.ConclusionsOur study corroborates GOG 150 results, and shows that paclitaxel-carboplatin appears to be an efficacious adjuvant chemotherapy regimen for completely resected uterine carcinosarcoma. The role of adjuvant RT in addition to chemotherapy warrants further investigation.     

Implementing change in a long stay hospital using an individual review system

This article describes the process of implementing change to an individual review system in a long-stay hospital. A new review system was devised, piloted, and evaluated. Despite the constraints of the institution (such as large size, and limited resources of staff and time) substantial improvements were made over a two-year period.     

Study of Two Techniques for Midline Laparotomy Fascial Wound Closure

To study the results of two techniques, simple interrupted closure and continuous with intermittent Aberdeen knot technique for midline laparotomy fascial wound closure. A random selection of 200 midline laparotomy cases was done. In one group (group A) of 100 cases, midline fascial wound closure was done with continuous sutures with intermittent Aberdeen knot technique using Prolene No. 1 suture material. In the other group (group B) of 100 cases, closure was done with the technique of simple interrupted sutures with Prolene No.1 suture material. Comparison of both the techniques regarding preoperative status and postoperative complication such as incisional hernia, wound dehiscence, suture sinus formation, stitch granuloma, and chronic wound pain was done according to clinical examination and recorded in the pro forma prepared. In group A, postoperative complications were incisional hernia 3 %, wound dehiscence 4 %, and suture sinus formation 1 %. In group B, postoperative complication were incisional hernia 5 %, wound dehiscence 4 %, and suture sinus formation 1 %. All these complications were statistically insignificant, in both group comparisons. While the complication such as stitch granuloma 3 %, chronic wound pain 3 %, and wound infection 4 % in group A was significantly less than in group B where the complication of stitch granuloma was 12 %, chronic wound pain 13 %, and wound infection 13 % (P value 0.03, P value 0.018, and P value 0.048, respectively). Both the techniques, simple interrupted suture closure and continuous with intermittent Aberdeen knot closure for midline laparotomy fascial wounds, show a similar rate of postoperative complication such as incisional hernia, wound dehiscence, and suture sinus formation. But the continuous suturing with intermittent Aberdeen knot technique is a better option to prevent complications such as stitch granuloma, chronic wound pain, and wound infection, which are higher in the simple interrupted fascial wound closure technique.     

A lentivirally delivered photoactivatable GFP to assess continuity in the endoplasmic reticulum of neurones and glia

The endoplasmic reticulum (ER) is the largest intracellular membranous organelle. Functions of the ER are many and diverse, which include various biosynthetic, transport and signalling roles, central to cellular physiology, such as the biosynthesis of membrane and secretory proteins and the regulation of intracellular calcium. Its continuous lumen also serves as a highway for the distribution of proteins and ions to different regions of the cell, independent of the cytosol. The ER is an excitable organelle, capable of generating a regenerative wave of calcium release, which can propagate along the endomembrane throughout the entire cell, serving as a system of intracelluar communication in polarised cells. Nowhere is this feature of ER function more crucial than in neurones. The extremely polarised nature of nerve cells presents a unique challenge for the global co-ordination of localised physiological events such as growth cone guidance and synaptic plasticity. Clearly, the physical continuity of the neuronal ER lumen is central to its functionality as a conduit for communication. To further probe the continuity of ER in neurones and glia, we developed LV-PA-pIN-KDEL, a photoactivatable analogue of our recently described vector LV-pIN-KDEL, a lentivirally delivered ER-targeting soluble GFP. We demonstrate the ability of this vector to transduce astrocytes and neurones in culture and in cortical explants. Furthermore, we exploit the photoactivatable attributes of the vector together with a focal laser photoactivation protocol to reveal the continuous nature of the ER lumen in these cell types, presenting the first direct evidence of an astrocytic ER luminal continuum and providing more data to support the existence of a single ER lumen in neurones. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Major lower limb amputation – what,why and how to achieve the best results

This article is intended as an overview of rehabilitation following major lower limb amputation; which surgical techniques can improve outcomes, why they should be considered and how the rehabilitation team works once patients have left the care of the surgical team. It is aimed primarily at orthopaedic and trauma surgeons, but also contains references to dysvascular patients, as this is the primary cause of lower limb amputation in the UK. The different aspects of rehabilitation after an amputation will be presented using the World Health Organization’s international classification of functioning, disability and health. The domain of health condition includes the aetiology of amputation and a brief history of prosthetic provision. The impairment section covers surgical techniques and how they can help improve outcomes for patients along with pre and post-operative pain management. An activity section contains an introduction to physiotherapy and early walking aids, with an overview of prosthetic assessment and the common component types. The participation section goes into appropriate goal setting and realistic outcomes that patients can expect. The final section on social and environmental factors briefly covers psychology and motivation. A vignette of key learning points concludes the article.     

Congenital cutaneous lymphadenoma

Cutaneous lymphadenoma is an uncommon benign neoplasm often considered to be an adamantinoid variant of trichoblastoma. Lesions present in both sexes, between 14 and 87 years of age, and are mainly located on the head and neck. Cases in children are rare and there is only 1 previous case of a congenital lymphadenoma. An 8‐year‐old Asian girl presented with a congenital lesion on her forehead comprising 4 pink papules, the largest 5 mm in diameter. Microscopy revealed a well‐circumscribed tumor within the dermis and subcutis comprising well‐demarcated epithelial lobules of basaloid and clear cells with subtle peripheral palisading, growing in a collagenous stroma but lacking retraction artefact. A relatively dense accompanying predominantly lymphocytic inflammatory cell infiltrate including both T‐cells (CD3+) and B‐cells (CD20+) permeated the nodules and spilled into the stroma. CD68+ histiocytes and CD1a+ Langerhans cells were moderately numerous. This is the second case of congenital lymphadenoma which—in spite of its rarity in childhood—widens the diagnostic possibilities of cutaneous lymphoepithelial tumors in children.