Composite t(14;18)-Negative Follicular Lymphoma and Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

A composite lymphoma is the rare simultaneous occurrence of two or more distinct lymphomas within a single tissue or organ. Herein, we describe a case of a 51-year-old man presenting with a history of lower limb rash, fatigue, and bulky abdominopelvic lymphadenopathy. An excisional left iliac lymph node biopsy was notable for the composite presence of two distinct lymphoid neoplasms, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), and follicular lymphoma (FL). Multiplex PCR and FISH analyses failed to demonstrate a t(14;18)(q32;q21) translocation in either composite lymphoma component. A clonal light-chain kappa (V/JC intron-kde) gene rearrangement was detected in the FL component only.

Composite Blastoid Variant of Mantle Cell Lymphoma and Classical Hodgkin Lymphoma.

Composite lymphoma (CL) describes the rare occurrence of 2 or more distinct types of lymphoma in a single anatomical location. We present the case of a 78-year-old man presenting with a 3-month history of weakness, malaise, and increasing dyspnea. A lymph node excised from the posterior triangle of the neck revealed the coexistence of 2 morphologically and phenotypically distinct lymphoid neoplasms consistent with a blastoid variant of mantle cell lymphoma (MCL) occurring in composite with classical Hodgkin lymphoma (cHL), mixed cellularity subtype. A t(11;14)(q13;q32) translocation was demonstrated by fluorescence in situ hybridization in the MCL and Hodgkin Reed-Sternberg cells of the cHL. Multiplex polymerase chain reaction detected clonal Immunoglobulin heavy chain (VFR1-J, VFR2-J, and VFR3-J), clonal immunoglobulin light chain kappa (V-J and V/JC intron-kde) and clonal immunoglobulin light chain lambda (V-J) gene rearrangements in the MCL. This report represents the first case of a blastoid variant of MCL occurring in composite with cHL.

Classical Hodgkin Lymphoma Arising Adjacent to a Breast Implant.

Breast implant-associated lymphoma has recently gained wide recognition. Anaplastic large cell lymphoma (ALCL) is the most frequently diagnosed subtype in this setting but the spectrum is broadening. A 66-year-old woman developed swelling and itch around her saline implant 6 years after its insertion. Imaging revealed a fluid collection surrounding the implant with an adjacent mass. Microscopy showed sclerotic tissue punctuated by discrete cellular nodules comprising small lymphocytes, eosinophils and interspersed large atypical Hodgkin Reed-Sternberg (HRS)-like cells. The HRS-like cells stained positively for CD30 and CD15 by immunohistochemistry. Small T-lymphocytes formed rosettes around HRS-like cells. Appearances were consistent with classical Hodgkin lymphoma (HL). Multiplex polymerase chain reaction demonstrated no clonal rearrangements of immunoglobulin or T-cell receptor genes, however, a t(14;18)(q32;q21)BCL2-JH translocation involving the major breakpoint region of the bcl2 gene was present. Staging positron emission tomography-computed tomography scan revealed FDG-avid masses in the right axilla and pelvis. Subsequent pathological examination identified low-grade follicular lymphoma (FL) with a t(14;18) translocation at these sites. To our knowledge, this is the first case of HL arising adjacent to a breast implant. An awareness of this diagnosis is important as classical HL, with its prominent mixed inflammatory background, may be overlooked as a reactive process when histologically assessing capsulectomy specimens. It is also important in the differential diagnosis for implant-associated ALCL as both contain large atypical CD30-positive cells highlighting the need for full immunohistochemical and molecular workup in such cases. This case also adds to the large body of literature regarding the association between HL and FL.

Opening Residents' Notes to Patients: A Qualitative Study of Resident and Faculty Physician Attitudes on Open Notes Implementation in Graduate Medical Education.

PURPOSE: OpenNotes is a growing national initiative inviting patients to read clinician progress notes (open notes) through a secure electronic portal. The goals of this study were to (1) identify resident and faculty preceptor attitudes about sharing notes with patients, and (2) assess specific educational needs, policy recommendations, and approaches to facilitate open notes implementation. METHOD: This was a qualitative study using focus groups with residents and faculty physicians who supervise residents, representing primary care, general surgery, surgical and procedural specialties, and nonprocedural specialties, from Beth Israel Deaconess Medical Center and Geisinger Health System in spring 2013. Data were audio recorded and transcribed verbatim, then coded and organized into themes. RESULTS: Thirty-six clinicians (24 [66.7%] residents and 12 [33.3%] faculty physicians) participated. Four main themes emerged: (1) implications of full transparency, (2) note audiences and ideology, (3) trust between patients and doctors, and (4) time pressures. Residents and faculty discussed how open notes might yield more engaged patients and better notes but were concerned about the time needed to edit notes and respond to patient inquiries. Residents were uncertain how much detail they should share with patients and were concerned about the potential to harm the patient-doctor relationship. Residents and faculty offered several recommendations for open notes implementation. CONCLUSIONS: Overall, participants were ambivalent about resident participation in open notes. Residents and faculty identified clinical and educational benefits to open notes but were concerned about potential effects on the patient-doctor relationship, requirements for oversight, and increased workload and burnout.

Case Study: Diffuse Large B-Cell Lymphoma Arising in Ovarian Mature Cystic Teratoma.

We describe an unexpected finding of diffuse large B-cell lymphoma associated with mature cystic teratoma of the ovary. A 68-yr-old woman with a complex left ovarian cystic mass on imaging underwent bilateral salpingo-oophorectomy, lymphadenectomy, appendicectomy, and omentectomy. Histopathologic examination revealed nodules of malignant non-Hodgkin lymphoma within the teratoma. A diagnosis of diffuse large B-cell lymphoma, germinal center cell subtype by Hans criteria was made after immunostaining and molecular studies. The patient was treated with R-CHOP chemotherapy and remains disease-free at 14-mo follow-up.

The prevalence of Vitamin D deficiency is higher in adult survivors of childhood cancer.

BACKGROUND: It is unclear whether the rate of vitamin D deficiency in paediatric cancer survivors is higher than in the background population, and whether this is of pathological significance. PATIENTS AND METHODS: 25OHD was measured in a previously studied group of 208 survivors (n = 108 paediatric 5-17 years, n = 99 adults 18-39 years) and compared with paediatric (5-17 years; n = 132) and adult controls (25-35 years; n = 1393 from the AusDiab cohort) adjusted for age and gender. Relationships with treatment factors (irradiation, bone marrow transplantation and intensity of treatment) along with overweight/obesity (defined by BMI), abdominal adiposity (waist:height ratio >0·5) and hyperinsulinism or abnormal glucose tolerance (HI/aGT) were sought. RESULTS: 25OHD concentrations were similar in paediatric survivors compared with controls (64·3 ± 21·6 nmol/l vs 66·3 ± 22·8 nmol/l), with no effect of age or gender. Adjusted for gender, rates of 25OHD deficiency (<50 nmol/l) were higher in adult survivors compared with AusDiab controls (42·4% vs 20·8%; P < 0·001). Apart from time since diagnosis (P = 0·03), no relationship with treatment factors was detected. In multivariate regression analysis, abdominal adiposity (P = 0·001), but not overweight/obesity by BMI status nor HI/aGT, was associated with significantly lower 25OHD concentrations. CONCLUSIONS: Adult survivors are at increased risk of abnormalities in vitamin D compared to the background population, probably reflecting longer time since diagnosis. Like others, we have not identified any contributory treatment-related factors. Vitamin D deficiency does not appear to be associated with the development of abnormal glucose tolerance in this population.

Effects of spiritual healing for women undergoing long-term hormone therapy for breast cancer: a qualitative investigation.

BACKGROUND: Spiritual Healing is widely available and used, but is a neglected area for research and its biologic and psychologic mechanisms are not understood. The side-effects of long-term hormonal therapy for breast cancer are onerous and have been reported to lead to "drug holidays" that could diminish the long-term treatment benefits. It was investigated whether Spiritual Healing could support patients with breast cancer undergoing this treatment. METHODS: The qualitative observation study took place in a specialist research facility in a general hospital. Spiritual Healing was provided by 4 healers registered with the National Federation of Spiritual Healers. Twelve (12) patients with breast cancer undergoing long-term hormone treatment and who found the effects onerous, self-referred themselves and were given ten weekly sessions of approximately 40 minutes each. Data collected included participant's daily records, direct observations noted by healers, the researcher's field diary and a one-to-one semi-structured interview. FINDINGS: The positive effects of Spiritual Healing included alleviation of the physical side-effects of their treatment, increased energy levels, enhanced well-being, emotional relaxation, and re-engagement with precancer activities. Although 1 participant admitted considering a drug holiday prior to joining the study, none of the participants felt tempted to stop their hormonal treatments while receiving Spiritual Healing. CONCLUSIONS: These qualitative findings indicate that Spiritual Healing has the potential to support patients with breast cancer in the maintenance of their long-term orthodox treatments. Further research is needed to test Spiritual Healing as a cost-effective complementary therapy, for those undergoing long-term cancer treatments.

Inviting patients to read their doctors' notes: a quasi-experimental study and a look ahead.

BACKGROUND: Little information exists about what primary care physicians (PCPs) and patients experience if patients are invited to read their doctors' office notes. OBJECTIVE: To evaluate the effect on doctors and patients of facilitating patient access to visit notes over secure Internet portals. DESIGN: Quasi-experimental trial of PCPs and patient volunteers in a year-long program that provided patients with electronic links to their doctors' notes. SETTING: Primary care practices at Beth Israel Deaconess Medical Center (BIDMC) in Massachusetts, Geisinger Health System (GHS) in Pennsylvania, and Harborview Medical Center (HMC) in Washington. PARTICIPANTS: 105 PCPs and 13,564 of their patients who had at least 1 completed note available during the intervention period. MEASUREMENTS: Portal use and electronic messaging by patients and surveys focusing on participants' perceptions of behaviors, benefits, and negative consequences. RESULTS: 11,155 [corrected] of 13,564 patients with visit notes available opened at least 1 note (84% at BIDMC, 82% [corrected] at GHS, and 47% at HMC). Of 5219 [corrected] patients who opened at least 1 note and completed a postintervention survey, 77% to 59% [corrected] across the 3 sites reported that open notes helped them feel more in control of their care; 60% to 78% of those taking medications reported increased medication adherence; 26% to 36% had privacy concerns; 1% to 8% reported that the notes caused confusion, worry, or offense; and 20% to 42% reported sharing notes with others. The volume of electronic messages from patients did not change. After the intervention, few doctors reported longer visits (0% to 5%) or more time addressing patients' questions outside of visits (0% to 8%), with practice size having little effect; 3% to 36% of doctors reported changing documentation content; and 0% to 21% reported taking more time writing notes. Looking ahead, 59% to 62% of patients believed that they should be able to add comments to a doctor's note. One out of 3 patients believed that they should be able to approve the notes' contents, but 85% to 96% of doctors did not agree. At the end of the experimental period, 99% of patients wanted open notes to continue and no doctor elected to stop. LIMITATIONS: Only 3 geographic areas were represented, and most participants were experienced in using portals. Doctors volunteering to participate and patients using portals and completing surveys may tend to offer favorable feedback, and the response rate of the patient surveys (41%) may further limit generalizability. CONCLUSION: Patients accessed visit notes frequently, a large majority reported clinically relevant benefits and minimal concerns, and virtually all patients wanted the practice to continue. With doctors experiencing no more than a modest effect on their work lives, open notes seem worthy of widespread adoption. PRIMARY FUNDING SOURCE: The Robert Wood Johnson Foundation, the Drane Family Fund, the Richard and Florence Koplow Charitable Foundation, and the National Cancer Institute.

Home blood sodium monitoring, sliding-scale fluid prescription and subcutaneous DDAVP for infantile diabetes insipidus with impaired thirst mechanism.

BACKGROUND/AIMS: Infants with diabetes insipidus (DI), especially those with impaired thirst mechanism or hypothalamic hyperphagia, are prone to severe sodium fluctuations, often requiring hospitalization. We aimed to avoid dangerous fluctuations in serum sodium and improve parental independence. METHODS: A 16-month old girl with central DI, absent thirst mechanism and hyperphagia following surgery for hypothalamic astrocytoma had erratic absorption of oral DDAVP during chemotherapy cycles. She required prolonged hospitalizations for hypernatremia and hyponatremic seizure. Intensive monitoring of fluid balance, weight and clinical assessment of hydration were not helpful in predicting serum sodium. Discharge home was deemed unsafe. Oral DDAVP was switched to subcutaneous (twice-daily injections, starting with 0.01mcg/dose, increasing to 0.024mcg/dose). The parents adjusted daily fluid allocation by sliding-scale, according to the blood sodium level (measured by handheld i-STAT analyser, Abbott). We adjusted the DDAVP dose if fluid allocation differed from maintenance requirements for 3 consecutive days. RESULTS: After 2.5 months, sodium was better controlled, with 84% of levels within reference range (135-145 mmol/L) vs. only 51% on the old regimen (p = 0.0001). The sodium ranged from 132-154 mmol/L, compared to 120-156 on the old regimen. She was discharged home. CONCLUSION: This practical regimen improved sodium control, parental independence, and allowed discharge home.

Once daily insulin detemir in cystic fibrosis with insulin deficiency.

The aim of this study was to determine if once daily insulin detemir reverses decline in weight and lung function in patients with cystic fibrosis (CF). 12 patients with early insulin deficiency and six with CF related diabetes (aged 7.2-18.1 years) were treated for a median of 0.8 years. Changes in weight and lung function following treatment were compared to pretreatment changes. Before treatment, the change in weight SD score (ΔWtSDS), percentage of predicted forced expiratory volume in 1 s (Δ%FEV(1)) and percentage of predicted forced vital capacity (Δ%FVC) declined in the whole study population (-0.45±0.38, -7.9±12.8%, -5.8±14.3%) and in the subgroup with early insulin deficiency (-0.41±0.43, -9.8±9.3%, -6.8±10.3%). Following treatment with insulin ΔWtSDS, Δ%FEV(1) and Δ%FVC significantly improved in the whole study population (+0.18±0.29 SDS, p=0.0001; +3.7±10.6%, p=0.007; +5.2±12.7%, p=0.013) and in patients with early insulin deficiency (+0.22±0.31 SDS, p=0.003; +5.3±11.5%, p=0.004; +5.8±13.4%, p=0.024). Randomised controlled trials are now needed.

Forging convictions: the effects of active participation in a clinical trial.

This qualitative study explored non-specific influences on participation in, and outcomes of, a randomised controlled trial. It was nested within a single-blind clinical trial of western acupuncture which compared real acupuncture with two types of placebo control administered to National Health Service (NHS) patients awaiting hip and knee replacement surgery in England. Data collection (2004-2008) was based on narrative-style interviews and participant observation. The results indicate that trial recruitment and retention depend on a set of convictions forged largely as a result of contextual factors peripheral to the intervention, including the friendliness and helpfulness of research centre staff and status of the administering practitioner. These convictions also influence the reporting of the study outcomes, particularly if participants experience uncertainties when choosing an appropriate response. The findings suggest that participants in clinical trials are actively involved in shaping the research process, rather than passive recipients of treatment. Thus the outcomes of trials, notably those involving contact interventions, should be regarded not as matters of fact, but as products of complex environmental, social, interpretive and biological processes. In this paper, we develop and present a 'theory of active research participation' which offers a framework for understanding the impact of non-specific processes in clinical trials.

The development and validation of an outcome measure for spiritual healing: a mixed methods study.

BACKGROUND: Spiritual healing, probably the oldest documented paramedical intervention, is a neglected area of research. In order to conduct further research into the effects of healing, a valid and reliable outcome measure is needed that captures the experience of individuals receiving healing (healees) and is not burdensome to complete. We aimed to develop such a measure. METHODS: A mixed methods design was used. Focus groups and cognitive interviews were used to generate and refine questionnaire items grounded in the experiences and language of healees (Study 1). The resulting questionnaire was tested and its formal psychometric properties were evaluated (Study 2). Participants were recruited from a spiritual healing sanctuary and via individual healers (including registered spiritual healers, Reiki practitioners, healers affiliated with churches). RESULTS: In Study 1, 24 participants took part in 7 focus groups and 6 cognitive interviews. 29 common effects were identified and grouped into 7 discrete dimensions that appeared to characterize potentially sustainable effects reported by participants following their experiences of spiritual healing. In Study 2, 393 participants returned completed baseline questionnaires, 243 of whom completed the questionnaire again 1-6 weeks later. Exploratory factor analysis generated 5 subscales, based on 20 of the items: outlook, energy, health, relationships and emotional balance. These subscales demonstrated acceptable internal consistency, convergent validity and test-retest reliability. Three of the subscales and the whole questionnaire demonstrated good sensitivity to change. CONCLUSIONS: We have produced a psychometrically sound healing impact questionnaire that is acceptable to healees, healers and researchers for use in future evaluations of spiritual healing.

Prevention of hyponatremia during maintenance intravenous fluid administration: a prospective randomized study of fluid type versus fluid rate.

OBJECTIVES: To determine the importance of sodium content versus administration rate of intravenous fluids in the development of hyponatremia in postoperative children. STUDY DESIGN: In this prospective, randomized, nonblinded study, 124 children admitted for surgery received 0.9% (NS) or 0.45% (N/2) saline solution at 100% or 50% maintenance rates. Plasma electrolytes, osmolality, and ADH at induction of anesthesia were compared with values 8 hours (T(8)), and 24 hours (T(24); n = 67) after surgery. Blood glucose and ketones were measured every 4 hours. Electrolytes and osmolality were measured in urine samples. RESULTS: Plasma sodium concentrations fell in both N/2 groups at T(8) (100%: -1.5 +/- 2.3 mmol/L 50%: -1.9 +/- 2.0 mmol/L; P < .01) with hyponatremia more common than in the NS groups at T(8) (30% vs 10%; P = .02) but not T(24). Median plasma antidiuretic hormone concentrations increased 2- to 4-fold during surgery (P < or = .001) and only reattained levels at induction of anesthesia by T(24) in the N/2 100% group. On multiple linear regression analysis, fluid type, not rate determined risk of hyponatremia (P < .04). Two children on 100% developed SIADH (1NS). Fourteen (23%; 7NS) on 50% maintenance were assessed as dehydrated. Dextrose content was increased in 18 for hypoglycemia or ketosis. CONCLUSIONS: The risk of hyponatremia was decreased by isotonic saline solution but not fluid restriction.

A proteomic analysis of the salt, cadmium and peroxide stress responses in Candida albicans and the role of the Hog1 stress-activated MAPK in regulating the stress-induced proteome.

Stress responses are important for the virulence of the major fungal pathogen of humans, Candida albicans. In this study we employed a 2-DE approach to examine the impact of exposure to peroxide (5 mM H(2)O(2)), salt (300 mM NaCl) or cadmium stress (0.5 mM Cd(2+)) upon the C. albicans proteome. Highly reproducible changes in the C. albicans proteome were observed in response to each stress condition. Significantly more proteins were up-regulated in response to cadmium (77) than to the salt (35) or peroxide stresses (35). These proteomic changes displayed minimal overlap with those observed in the transcriptome under equivalent conditions and, importantly, revealed functional categories that respond to stress at the protein level but not the transcript level. Six proteins were up-regulated by all three conditions: Adh1, Atp2, Cip1, Eft2, Ssa1 and Ssb1, which is consistent with the concept that a core stress response exists in C. albicans. This is the first time that a fungal core stress response has been defined at the proteomic level. We have also shown that the Hog1 stress-activated mitogen-activated protein kinase, which is activated in response to the stresses examined in this study, makes a major contribution to the C. albicans stress proteome.

Rapamycin treatment for a child with germline PTEN mutation.

BACKGROUND: A 9-month-old boy with Proteus syndrome and a de novo germline mutation in the tumor suppressor PTEN was referred to a specialist centre for management. Over the first years of life, the patient developed life-threatening respiratory dysfunction and malnutrition because of progressive growth of hamartomas affecting the chest, mediastinum, abdomen and pelvis. INVESTIGATIONS: Physical examination, CT scans of the mediastinum, pelvis and abdomen, measurement of serum insulin-like growth factor binding protein-2, and investigation of the effect of the PTEN mutation on phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling in an in vitro cell model. DIAGNOSIS: PTEN hamartoma tumor syndrome, specifically Proteus syndrome. MANAGEMENT: Oral rapamycin.

Experience of proximate spiritual healing in women with breast cancer, who are receiving long-term hormonal therapy.

BACKGROUND: This paper presents the research protocol for a pragmatic study of the experience of spiritual healing. This unique qualitative study seeks to identify any qualitative benefits of hands-on or proximate spiritual healing for women experiencing adverse reactions to hormonal treatments. Healing will be administered as adjuvant therapy for the long-term management of breast cancer. DESIGN: A purposive sample of up to 20 women who have completed their initial treatments at least 6 months previously will be recruited through the Oncology Department at Southampton General Hospital. The study will take place at the Wellcome Trust Clinical Research Facility within Southampton General Hospital, where spiritual healing will be provided by healers who are National Federation of Spiritual Healers registered. Patients will be offered up to 10 weekly healing sessions. OUTCOME: Patients will be asked to keep a daily log noting any changes they have noticed during or after the healing sessions and their attributions of these. Audio recorded in-depth interviews will be carried out after completion of the final healing. Participants will also be invited to attend focus group meetings to discuss any effects of healing. Data will be analyzed initially using an ethnographic approach allowing further analysis using other appropriate qualitative methodologies. Depending on the findings, this study will also form the preliminary stage of a further study to develop and evaluate a healing-specific questionnaire.