Excellent Quality Of Life Research Articles

Ayurvedic management of COVID-19/SARS-CoV-2 along with chronic diabetes mellitus: A case study

Introduction: SARS-CoV-2, a global pandemic that caused significant morbidity and mortality worldwide, even in the second wave. Multiple factors influence the disease burden including the vicious circulating virus characteristics, complications, limitations of the existing medicine, aggravation of the disease, and comorbidities in older people. In the present scenario, effective traditional treatment modalities should be scientifically applied to reduce massive disasters. Objectives: Here is the necessity to develop an appropriate treatment protocol from the field of Ayurvedic medicine. Diagnosis: It is a case study of a confirmed case of COVID-19/SARS-CoV-2 with uncontrolled diabetic history. Significant Clinical Findings: Presented intermittent fever, cough, headache, and dyspnea, along with symptoms associated with diabetes mellitus. Interventions: The case was successfully managed with Ama pachana (~carminative), Agnideepana (digestive), Jwara hara Oushdha, and simultaneously Prameha (~diabetes mellitus). Outcomes: The entire treatment course competed with a minimum number of hospitals stay compared with the national average. Ayurvedic management has a significant positive impact on the mental and physical quality of life. Both physical and mental scores got improved by more than 50% in this case. Marked radiological improvement noted, in this case, is associated with excellent quality of life after treatment. Conclusion: Ayurvedic management can be used in multiple levels preventive, curative, and restorative aspects.

Identification and relationship of quality of life and self-care ability among Chinese patients with traumatic spinal cord injuries: a cross-sectional analysis.

Improving the quality of life of patients with complete spinal cord injuries is an urgent objective of the Chinese Department of Health. For better management of spinal cord injuries, it is necessary to understand the background of the patients. A total of 392 patients aged ≥18 years with traumatic spinal cord injuries (≥1 year of history) were attending the rehabilitation center of the Institutes. A total of 7 (2%) patients reported low quality of life, 200 (51%) patients reported moderate quality of life, 181 (46%) patients reported good quality of life, and 4 (1%) patients reported excellent quality of life. Male patients (P=0.042), patients with college or more education (P=0.039), incomplete spinal cord injuries (P=0.045), paraplegia (P=0.046), and absence of pressure injury (P=0.047) were associated with higher quality of life. A total of 81 (21%) patients were dependent on the caregiver, 85 (22%) patients were highly dependent on the caregiver, 155 (40%) patients were moderately dependent on the caregiver, 60 (15%) patients were mildly dependent on the caregiver, and 11 (2%) patients were independent for activities of daily living. An incomplete spinal cord injury (P=0.045) and paraplegia (P=0.041) were associated with higher independence in activities of daily living of patients. The independence in activities of daily living and quality of life of the Chinese population with complete spinal cord injury and tetraplegia are poor (Level of Evidence: IV; Technical Efficacy Stage: 5).

Associations Between Mobile Health Technology use and Self-rated Quality of Life: A Cross-sectional Study on Older Adults with Cognitive Impairment

Background: Quality of life (QoL) is affected even at early stages in older adults with cognitive impairment. The use of mobile health (mHealth) technology can offer support in daily life and improve the physical and mental health of older adults. However, a clarification of how mHealth technology can be used to support the QoL of older adults with cognitive impairment is needed. Objective: To investigate factors affecting mHealth technology use in relation to self-rated QoL among older adults with cognitive impairment. Methods: A cross-sectional research design was used to analyse mHealth technology use and QoL in 1,082 older participants. Baseline data were used from a multi-centered randomized controlled trial including QoL, measured by the Quality of Life in Alzheimer’s Disease (QoL-AD) Scale, as the outcome variable. Data were analyzed using logistic regression models. Results: Having moderately or high technical skills in using mHealth technology and using the internet via mHealth technology on a daily or weekly basis was associated with good to excellent QoL in older adults with cognitive impairment. Conclusions: The variation in technical skills and internet use among the participants can be interpreted as an obstacle for mHealth technology to support QoL.

RARE-40. CASE REPORT: LONG-TERM SURVIVOR OF A RARE, PEDIATRIC PRIMARY HISTIOCYTIC SARCOMA (HS) OF THE CENTRAL NERVOUS SYSTEM (CNS) FOLLOWING COMPLETE RESECTION, CHEMOTHERAPY AND ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (ALLO-HCT)

We report an unusual case of a patient with primary CNS-HS a very rare neoplasm of histiocytic lineage with usually poor prognosis. An 8 year old boy presented with a one month history of headaches, nausea and vomiting. Physical examination revealed nystagmus and dysmetria. Brain MRI revealed a localized 2.4 cm posterior fossa (cerebellar) mass with restricted diffusion. The patient underwent a gross total resection of the mass. Initial post-operative lumbar puncture was positive for rare malignant cells. Pathology showed a focally necrotic neoplasm, composed of nests and cords of large relatively uniform cells with abundant eosinophilic cytoplasm, moderately pleomorphic nuclei and numerous mitotic figures, consistent with CNS-HS with juvenile xanthogranuloma phenotype, as supported by positive IHC expression of CD163, CD68, CD14, fascin, and Factor XIIIa, while negative for CD1a, Lymphoid and Myeloid markers, and BRAFv600e mutation. He was treated with two cycles of clofarabine and cytarabine and triple intrathecal (IT) chemotherapy. He developed generalized seizures and MRI showed demyelination consistent with IT methotrexate toxicity; MTX was then discontinued. He was then given two additional cycles of cladribine and weekly intrathecal therapy prior to consolidation with an Allo-HCT using a 10/10 HLA allelic-matched unrelated donor. His conditioning regimen included total body irradiation and cyclophosphamide. He did well post-transplant with peripheral blood chimerism at 1 year showing > 95% donor cells. He remains disease-free with an excellent quality of life since August 2016. We report one of the few known survivors of this unusual and highly malignant entity.

Successful Treatment by Mistletoe Viscum Album Extract of a Patient with Recurrent Triple Negative Breast Cancer who declined Chemotherapy

Triple negative breast cancer (TNBC) is an aggressive breast cancer with a high incidence of recurrence and poor prognosis even with the full spectrum of standard oncology treatments. Ever since its introduction about 100 years ago for cancer therapy, mistletoe viscum album extract (VAE) has been widely used in Europe as a popular complementary therapy for many cancers. We present a case of a patient diagnosed with stage 3c (T3N3bM0(i+)) TNBC who declined chemotherapy after a recurrence 2 years later. The patient received subcutaneous, intratumoral as well as intravenous VAE therapy for her recurrence. Her breast masses and lymph node sizes dramatically decreased under ultrasound examination within 2 months. After nearly three years since the tumor resolution, she is currently being managed on weekly subcutaneous VAE as well as intravenous VAE once in 6-8 weeks. She has excellent quality of life, no sign of tumor recurrence or other adverse side effects from her treatments. Though we believe the best outcomes in oncology are by integrating complementary and conventional care together, this case shows that VAE can have standalone effectiveness at least in some cases. Use of VAE to augment conventional treatments should be considered to bolster breast cancer care.

Colonic interposition, a contemporary experience: technical aspects and outcomes.

Colonic interposition is rarely used as an oesophageal replacement after resection, as the preferred use of stomach involves less anastomoses and lower risks of major complications. The functional outcome from the colonic conduit is also unpredictable. This report documents the spectrum of experience of a high-volume oesophageal centre, highlighting indications, techniques and functional outcomes. A retrospective review was undertaken of a prospective database from 2012 to 2016. Four of 252 (1.5%) cases in this time period utilised colon interposition. Two cases were for gastric conduit necrosis following oesophageal cancer resections, one for caustic ingestion with both an oesophago-bronchial fistula and gastric injury, and one for a primary oesophageal malignancy in a patient whom previously had a total gastrectomy. All patients had either a retrosternal or posterior mediastinal isoperistaltic right colon conduit placed. Two of three cancer patients are alive and disease free at 3 and 5years, respectively. Surviving patients are weight stable and tolerating a normal diet. Both report excellent quality of life using validated assessment tools. Colonic interposition is rarely required in modern oesophageal practice, but with this technique good long-term nutritional and functional outcomes can be obtained. It is required in the armamentarium of a specialist centre, and training given its rarity may require novel approaches such as simulation and cadaveric-based training.

In Utero Stem Cell Transplantation in Patients with Alpha Thalassemia Major: Interim Results of a Phase 1 Clinical Trial

Introduction: In utero hematopoietic cell transplantation (IUHCT) has the potential to treat patients with blood disorders by taking advantage of bidirectional maternal-fetal tolerance during pregnancy. Although engraftment has only been seen in immunodeficient patients in the past, recent preclinical studies indicate that a higher dose of maternal cells should be given intravascularly to maximize engraftment in other settings. We hypothesized that: 1) fetuses will tolerate a maternal IUHCT without conditioning and develop low engraftment with sustained tolerance to maternal alloantigens; and 2) tolerant patients could receive a postnatal booster maternal transplant with minimal immunoablative conditioning and thereby achieve a cure. To test the first of these hypotheses in a controlled setting, we have initiated a phase 1 clinical trial of IUHCT in fetuses with alpha thalassemia major (ATM), who already require a fetal intervention (in utero transfusions (IUT)) to survive the pregnancy. We present interim results from the first two patients. Methods: After obtaining IND approval, we initiated the clinical trial in 2017 (NCT02986698). Fetuses with ATM between 18-26 weeks' gestation without other major anomalies were included. To date, we have evaluated 19 patients for possible inclusion: 15 patients terminated the pregnancy, 2 patients were outside the inclusion window and underwent IUT alone, and 2 have been transplanted and completed the 1 year follow up. For IUHCT, 300 ml of maternal bone marrow was harvested, CD34+ cells were selected and transplanted fresh into the fetus via the umbilical vein, along with a standard IUT. IUTs were repeated every 3 weeks until delivery. Maternal cell chimerism was detected using qRT-PCR for non-inherited maternal HLA-DR alleles on sorted cell populations in cord blood and after birth. Mixed lymphocyte reactions (MLRs) were performed by culturing CFSE-labeled host CD4 and CD8 responder cells with maternal (or third-party) derived antigen presenting cells (APC; direct pathway) or self APC/maternal lysate (indirect pathway). Results: Both fetuses were diagnosed with severe hydrops on ultrasound and received an initial IUT prior to the IUHCT. Patient 1 was transplanted at 23 weeks with 1x 108CD34+ cells/kg + 1 x 107T cells/kg and Patient 2 was transplanted at 25 weeks with 5x 107CD34+ cells/kg + 5 x 106T cells/kg; both received 4 more IUTs until birth. Prenatal hydrops resolved in both and neonatal hospitalizations were 16 and 13 days, respectively. Maternal chimerism was detected in both patients, but levels were higher and persisted throughout the year only in patient 1 (Fig 1A). We detected 70-fold higher levels of erythrocyte precursors (Fig 1B) but normal levels of CD34+ cells in the cord blood of patients compared to healthy controls, highlighting a potential barrier to engraftment in a disease with prenatal hypoxia. Patient 1 demonstrated sustained tolerance to maternal antigens by MLR throughout the year, whereas patient 2 showed reactivity against maternal antigens (Fig 1C). HLA antibodies were negative in both. Based on the finding of donor-specific tolerance in patient 1, we offered a booster transplant with maternal cells but the parents declined. Both patients are undergoing monthly transfusions and have had normal development and Bayley neurologic testing at 1 year. There were no unanticipated safety events in either mother/child pair. Conclusions: These results demonstrate the safety of IUHCT in fetuses with ATM and the potential of fetal transplantation in the second trimester to sustain tolerance to maternal cells after birth. Low engraftment levels are predicted in the setting of host hyperproliferation and lack of space-making conditioning, confirming the need for a two-step strategy (IUHCT and postnatal booster transplant) for a definitive cure. The earlier transplantation in patient 1 enabled a higher dose of cells and may explain the improved outcome observed. Implementation of earlier screening in at-risk patient groups could allow earlier diagnosis and enrollment in the future. Although parents of fetuses with ATM are commonly counseled for pregnancy termination due to concern for poor outcomes, our results indicate that fetal therapy with IUTs can result in survival to term and excellent quality of life. This strategy of maternal IUHCT could be employed to treat fetuses with other hematologic disorders in the future. Figure 1 Disclosures MacKenzie: Acrigen: Membership on an entity's Board of Directors or advisory committees; Ultragenyx: Research Funding. Vichinsky:Global Blood Therapeutics: Consultancy; Agios: Research Funding; Pfizer: Research Funding.

Autologous stem cell transplantation following simultaneous liver and kidney transplantation in severe amyloid light chain amyloidosis associated with multiple myeloma: a case report

IntroductionThe involvement of vital organs in multiple myeloma (MM) with systemic amyloid light-chain (AL) amyloidosis can lead to acute organ failure. In this case, the fear of recurrence or progression of multiple myeloma often excludes those patients from undergoing organ transplantation. Nevertheless, clinically fit patients might benefit from a different therapeutic approach. This case presentation might highlight this particular unmet need and strengthen a different treatment approach.Case presentationTo our knowledge, we present the first case of successful simultaneous liver and kidney transplantation, followed by autologous stem cell transplantation in a 60-year-old Caucasian male patient suffering from MM (Durie-Salmon stage IIB; ISS-stage: III, RISS stage: III) with primary AL amyloidosis. Chemotherapy treatment led to end-stage kidney disease requiring dialysis. Liver failure also occurred after at least three cycles of CyBorD (bortezomib, cyclophosphamide, and dexamethasone) of induction therapy with a good hematologic response. Over three years after the initial diagnosis, the patient is reportedly showing an excellent quality of life and a complete remission.Discussion and ConclusionWe conclude that kidney and liver transplantation followed by autologous stem cell transplantation can be a treatment option for a selected group of patients with MM if AL amyloidosis is leading. In the end, the remission assessment by IMWG response criteria displayed a complete remission of MM together with complete reconstitution of organ functions (liver & renal function) as long as upfront clinical evaluation excludes significant cardiac involvement and other severe co-morbidities.

Three years prospective clinical and radiologic follow-up of laparoscopic sacrocolpoperineopexy.

When Rectocele is part of a complex pelvic organ prolapse, a full repair is recommended. The aim of this study was to evaluate the clinical and radiological results after laparoscopic surgery in patients with symptomatic rectocele and III/IV stage vaginal vault prolapse METHODS: This is a prospective cohort study of women with symptomatic rectoceles and middle compartment prolapse operated on between 2013 and 2015, who underwent a laparoscopic sacrocolpoperineopexy with synthetic Y mesh attached to puborectalis muscles, the anterior and posterior vagina wall and the sacrum. The clinical outcomes measured were symptoms of prolapse, obstructive defecation syndrome and quality of life. Radiological outcomes were distance of the vaginal vault below pubococcigeal line and depth of rectovaginal wall protrusion in dynamic pelvic resonance. 33 patients were included. 32 of them remained asymptomatic after a three years follow-up. Significant differences were shown in the obstructed defecation score and quality of life after 6, 12 and 36months compared to preoperatively. No differences were identified when the postoperative results were compared. Significant differences were shown in preoperative vaginal vault prolapse (3.2cms ± 0.8 SD below the pubococcigeal Line) and rectocele size, compared with 1 and 3years after surgery. There were no significant differences in vaginal vault prolapse when compared after 1 and 3years. When rectocele size after 1 and 3years was compared, significant differences were shown, but only one clinical recurrence (3%) was identified after a mean follow-up of 47months. Laparoscopic sacrocolpoperineopexy in patients with symptomatic rectocele and III/IV vaginal vault prolapse solves the constipation and obstructed defecation with an excellent quality of life and low clinical recurrences. Radiological deterioration, especially in rectocele size, was identified in the mid-term follow-up without clinical significance.

Clinical Veterinary Boron Neutron Capture Therapy (BNCT) Studies in Dogs with Head and Neck Cancer: Bridging the Gap between Translational and Clinical Studies.

Simple SummaryBoron Neutron Capture Therapy (BNCT) is a treatment for cancer based on the selective accumulation in tumor of boron compounds, followed by external irradiation with neutrons. The interaction between boron-10 and a neutron gives rise to very energetic particles that travel only a very short distance (approximately the diameter of a cell) and are lethal for the cell. In this way, BNCT damages tumor tissue selectively while preserving normal tissue. BNCT has proved effective to treat certain tumors in clinical trials worldwide, with room for improvement. Our group has worked on animal models to improve the efficacy of BNCT, in particular for head and neck cancer. Herein we performed clinical veterinary BNCT studies in five terminal dog patients with head and neck cancer with no other therapeutic option. In all cases we observed partial tumor response, clinical benefit, and extension of estimated survival time at recruitment with excellent quality of life. Toxicity associated to the treatment was mild/moderate and reversible. These studies contribute towards preparation for clinical BNCT trials for head and neck cancer in Argentina and suggest a potential role for BNCT in veterinary medicine.Translational Boron Neutron Capture Therapy (BNCT) studies performed by our group and clinical BNCT studies worldwide have shown the therapeutic efficacy of BNCT for head and neck cancer. The present BNCT studies in veterinary patients with head and neck cancer were performed to optimize the therapeutic efficacy of BNCT, contribute towards exploring the role of BNCT in veterinary medicine, put in place technical aspects for an upcoming clinical trial of BNCT for head and neck cancer at the RA-6 Nuclear Reactor, and assess the feasibility of employing the existing B2 beam to treat large, deep-seated tumors. Five dogs with head and neck cancer with no other therapeutic option were treated with two applications of BNCT mediated by boronophenyl-alanine (BPA) separated by 3–5 weeks. Two to three portals per BNCT application were used to achieve a potentially therapeutic dose over the tumor without exceeding normal tissue tolerance. Clinical and Computed Tomography results evidenced partial tumor control in all cases, with slight-moderate mucositis, excellent life quality, and prolongation in the survival time estimated at recruitment. These exploratory studies show the potential value of BNCT in veterinary medicine and contribute towards initiating a clinical BNCT trial for head and neck cancer at the RA-6 clinical facility.

Quality of Life and its Determinants in Heart Failure Patients at a Major Tertiary Academic Center in Ontario, Canada

Background Heart failure (HF) greatly impacts quality of life (QoL). Objectives We evaluated QoL, its determinants and associations with major outcomes in HF patients at our institution, Hamilton Health Sciences (HHS), a tertiary academic centre in Ontario. Methods We enrolled 270 patients in a HF registry with standardized recording of data on demographics, social and educational status, living conditions, HF etiology, symptoms, comorbidities, physical exam, medication use, ECG, echocardiographic and biochemical measurements. QoL was measured using the KCCQ-12 questionnaire. Patients are followed prospectively and at the time of this analysis all patients had completed 6 months follow-up. Results Patients' mean age was 70.6±11.2 yrs, 32% were women, 55.6% were married, 25.6% lived alone, 74.4% were enrolled from the outpatient HF clinic and 25.6% during a HF hospitalization. Mean LVEF was 40.1%, 53.2% had HFrEF, 30.3% HFpEF and 16.5% HFmEF. The most common HF etiology was IHD, 48.1% had NYHA class III or IV functional status and 64.4% had 2 or more comorbidities. Average KCCQ-12 summary score was 57.5±27.7, consistent with fair disability level and overall good QoL. 14.1% had severe disability (KCCQ-12 score between 0 and 25) and 33.3% had little or no disability and excellent QoL (KCCQ-12 score between 76 and 100). HFpEF patients had on average a lower KCCQ-12 summary score than HFrEF patients (53.2±28.6 vs. 58.1±27.1, p=0.027) and a higher proportion had a score of 25 or lower consistent with severe disability (21.4% vs. 11.4%). In bivariate analysis lower KCCQ-12 summary score was associated with older age, inpatient status, living alone, NYHA class, time from diagnosis of HF, history of diabetes, COPD, total number of comorbidities, LVEF, heart rate and BMI. However, in multivariate analysis only NYHA class III or IV, inpatient status and COPD emerged as independent predictors of a lower KCCQ-12 summary score. Patients in the upper third of KCCQ-12 scores had the lowest rates of HF hospitalizations, all-cause hospitalizations, CV death, all-cause death and the composite of HF hospitalization and all-cause death. Conclusions Inspite of living with HF, many patients in our registry have fair disability level and good QoL. Patients with HFpEF had worse QoL than those with HFrEF. Advanced NYHA class, inpatient status and COPD were independent predictors of poorer QoL. We observed a strong association between the KCCQ-12 summary score and major CV outcomes.

Personal Recovery from Serious Mental Illness

Personal rehabilitation from severe mental illness (SMI) refers to the cycle of living independent and active lives in the community, where individuals with significant mental disorders can be satisfactory. The aim of the concept analysis to clarify what is meant by a personal recovery of SMI internationally by the attributes, antecedents, and consequences. This study using a technique the analysis method of Walker & Avant through 8 steps techniques. The attributes of personal recovery of SMI include connectedness, hope and optimism about future, identity, meaning in life, and empowerment. Antecedents of personal recovery of SMI is a stigma attached to a mental health diagnosis. The consequences of personal recovery of SMI are usual from SMI, self-restoration, and excellent Quality of life. Symptom reduction (e.g., clinical recovery) becomes an integral part of someone's recovery if the person is something they want to be because recovery is unique for everyone.

First simultaneous and synchronized split-liver transplantation involving two recipients and three surgeons in Costa Rica: A case report

BackgroundCosta Rica has a public health system based on social security, and its transplant program has limited resources. Therefore, when a whole liver is surgically split for transplantation, only one of the obtained grafts can be transplanted. In Costa Rica, there are only three surgeons with expertise and surgical training in liver transplantation with living-donor and split-liver transplantation (SLT) for both pediatric and adult patients. To overcome the existing limitations and the low organ donation rate, a strategy designed to maximize the use of split grafts for liver transplantation was created. This strategy involves the performance of two simultaneous and synchronized SLTs in parallel at two different hospitals. MethodsThis strategy was performed for the first time in May 2018. Simultaneously and synchronously, two SLTs were performed for a woman and a female infant; both patients underwent operations at the same time by only three transplant surgeons in two different hospitals. ResultsThis strategy allowed the performance of two SLTs without compromising the cold ischemia time (CIT) or reperfusion. The infant and woman had a CIT time of 4.5 and 6.0 h, respectively. At 16 months postoperatively, both patients had excellent quality of life and graft function. ConclusionThis first experience with the herein-described surgical and logistical strategy, although successful, requires institutional and governmental support so that the outcomes can be improved to maximize the benefit and opportunity of access for patients on the waiting list for liver transplantation in health systems of third-world countries with limited resources.

Epilepsy Research in Mali: A Pilot Pharmacokinetics Study on First-Line Antiepileptic Drug Treatment.

Background and PurposeThe indication and benefit of plasma level of antiepileptic (AEDs) has been debating in the monitoring of people living with epilepsy and the epilepsy treatment gap has largely been documented in developed countries. This study was aimed to highlight the epilepsy treatment gap between rural and urban Mali.MethodsWe conducted a pilot study on AEDs treatment from September 2016 to May 2019. For 6 months, 120 children and young adults living with epilepsy (rural site, 90; urban site, 30) received phenobarbital, valproic acid and/or carbamazepine. At our rural study site, we determined the AED plasma levels, monitored the frequency, severity and the duration of seizure, and administered monthly the McGill quality of life questionnaire. At our urban study site, each patient underwent an electroencephalogram and brain computed tomography scan without close monitoring.ResultsAt the rural study site, patients were mostly on monotherapy; AED levels at 1 month (M1) (n=90) and at 3 months (M3) (n=27) after inclusion were normal in 50% at M1 versus 55.6% at M3, low in 42.2% at M1 versus 33.3% at M3 and high in 7.8% at M1 versus 11.1% at M3. AED levels at M1 and at M3 were significantly different p<0.0001. By M3, seizures (n=90) were <1/month in 26.7%, and lasted less than 1 minute in 16.7%. After a yearlong follow up, all 90 patients reported a good or excellent quality of life. At our urban study site, patients (n=30) were on carbamazepine and valproid acid in 66.67% and monotherapy (carbamazepine) in 33.33%. By November 2018, only six out 30 patients (on bi-therapy) were still taking their medications.ConclusionsEpilepsy diagnostic and treatment are a real concern in Mali. Our data showed appropriate AED treatment with close follow up resulted in a better quality of life of patients in rural Mali. We will promote the approach of personalized medicine in AED treatment in Mali.

Use of CD19-directed CAR T-Cell Therapy in an Infant With Refractory Acute Lymphoblastic Leukemia

Infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL) have historically poor outcomes despite maximal intensification of chemotherapy. Chimeric antigen receptor (CAR) T-cell therapy has revolutionized our approach to pediatric patients with relapsed/refractory ALL. Unfortunately, infants were excluded from early CAR T-cell trials due to concerns regarding the feasibility of T-cell collection and expansion. Here, we report the use of tisagenlecleucel in an infant with chemotherapy-refractory KMT2A-rearranged ALL. While CAR T-cell therapy was not curative for this patient, collection and expansion of T-cells proved feasible despite prior chemotherapy, he achieved minimal residual disease negative remission with excellent quality of life, and it facilitated a delay in hematopoietic stem cell transplantation.

Phase II study of ONC201 in pheochromocytoma-paragangliomas (PC-PG), medullary thyroid carcinoma (MTC), and other neuroendocrine tumors.

e16703 Background: ONC201 is an imipridone with specificity for the dopamine-like DRD2 receptor. Anti-cancer effects involve up-regulation of TRAIL/DR5, dual AKT/ERK pathway inhibition, and integrated stress response. Because TCGA analysis showed very high DRD2 expression in neuroendocrine tumors, especially pheochromocytoma-paragangliomas (PC-PG), an investigator initiated IND study of ONC201 in neuroendocrine tumors (CCF IRB17-808; CASE2716; IND132665; NCT03034200) was done. Methods: ONC201 dose was 625 mg po/wk. Metastatic PG-PG were enrolled in cohort A. Other neuroendocrine patients were entered in cohort B. Two additional patients had single patient IND. Because hypertension is an issue from catecholamine producing PC-PG, all PC-PG patients had combined alpha + beta blockade and bp was monitored in the clinical research unit after dose #1 ONC201. Additional data was obtained with daily home bp monitoring, often with a wireless cuff which connects into EPIC via MyChart. Labs, scans, and clinic visits were done at week 6, then every 3 months from initial ONC201 dose. Patients with clinical benefit remained on study and could get radiation for bone metastases. Results: Neuroendocrine tumors were treated with ONC201 included 10 PC-PG, 3 with MTC 13 with other varieties including sarcomas, adrenal cortical carcinoma (ACC), neuroblastoma, and GI neuroendocrine tumor (NET). ONC201 was exceptionally well tolerated. All patients were able to maintain or improve KPS while on study. No adverse effects on bp were seen. The only ONC201-related AE was temporary grade 1 neurocognitive dysfunction for ~36 hours after weekly ONC201 dosing in 2/10 PC-PG patients. 4/10 PC-PG patients remain on study at 28, 22, 22, and 4 month. 1 DSRCT patient achieved a PR at 3 months and has been treated 28 months. An ACC patient was initially responsive (PR), but rapidly progressed in liver; 1 GI NET patient had -10% reduction by RECIST at 3 months and remains on treatment. MTC may be responsive (1 no response, 2 stable and improving by RECIST at 3 months). Conclusions: ONC201 is very well tolerated with excellent quality of life and extended clinical benefit against neuroendocrine tumors. Although ONC201 has activity against neuroendocrine tumors, especially PC-PG, increased efficacy will likely require combination therapy. Clinical trial information: NCT03034200 . [Table: see text]

Assessing the personal impact of epilepsy in a population-based cohort of Veterans

PurposeEpilepsy impacts patient lives in multidimensional ways. Although previous work has investigated epilepsy impact on health status, little is known about the overall quantified impact of epilepsy in Veterans. Our goal was to describe the impact of epilepsy on Veterans' lives using the Personal Impact of Epilepsy Scale (PIES) and determine the patient and clinical characteristics most strongly correlated with epilepsy impact. We described cohort characteristics and developed regression models to determine which characteristics were most strongly associated with PIES subscale (seizure, medication, comorbidity) scores and quality of life (QOL). ResultsApproximately 36% of those who were invited responded to the survey. Of the 438 respondents included in the analyses, roughly 50% were aged 45–64 years (35% >65; 14% 18–44); 19% were women. Almost 90% had previously received care by an epilepsy specialist, 37% of which was in Veterans Health Administration (VHA) and 38% in both VHA and community. The PIES scores were moderately low (mean: 88.68, [standard deviation (SD) = 63.24]; 300 total). The PIES overall and subscale scores were significantly lower for older Veterans with epilepsy (VWE) (>65) compared with younger (18–44 years) and middle-aged (45–64 years) VWE [p < 0.001], indicating that older Veterans had a lower epilepsy impact overall, and for seizures, medication, and comorbidity. The younger and middle-aged VWE had a significantly higher proportion with psychiatric diagnosis compared with older VWE [p < 0.001]. There was a trend for significance for the overall PIES scores by gender, with women having total higher (worse) scores (mean = 93.10, SD = 69.68) than men (mean = 74.39, SD = 59.97), which was driven by a statistically higher score on the seizure subscale for women (mean = 27.66, SD = 27.97) compared with men (mean = 19.29, SD 25.35; p = 0.04). Regression models revealed that frequent seizures (>1/month, >2/month) and diagnoses of dementia significantly predicted higher (more negative) Seizure Severity PIES score [all p < 0.05]. Frequent seizures (>1/month), number of antiepileptic drugs (AEDs), and diagnosis of dementia predicted negative impact, and older age predicted positive impact for medication subscale. Frequent seizures (>1/month) and diagnoses of depression and dementia predicted negative mood and social impact [all p < 0.05]. Seizure frequency (>2/month) was the only variable that significantly predicted lack of excellent QOL [p < 0.05]. Effects for gender were not significant after controlling for other variables. ConclusionsFindings were similar to a prior study of generic health outcomes in younger and older VWE using the 36-Item Short Form Survey (SF-36). Seizure frequency was consistently associated with negative impact of epilepsy in all age groups. While dementia and other diagnosed health conditions also contributed to epilepsy impact, older VWE had significantly lower PIES scores even after controlling for physical conditions and dementia. Lower (better) scores for comorbidity and medication scales in older VWE may be due to fewer diagnosed psychiatric comorbidities and psychiatric medication that have similar cognitive impact as AEDs, and which may also interact with AEDs. Implementation of patient self-management programs to improve seizure control may reduce epilepsy impact for Veterans and reduce Veterans Affairs (VA) healthcare utilization. The PIES may also be useful to measure outcomes of self-management interventions.

Clinical, Cytological, Histopathological and Immunohistochemical Features of a T-Zone Lymphoma in a Mixed-Breed Dog

Background: Non-Hodgkin lymphoma are a group of lymphoid neoplasms originated from the proliferation of precursors or mature, T, B and/ or NK lymphocytes. T-Zone lymphoma (TZL) is characterized as an indolent lymphoma due to its slow progression and poor chemotherapy´s response. Dogs affected by this neoplasm may live for many years without clinical signs and are often underdiagnosed. The aim of the present article is report a TZL case in a nine-year old male mixed breed dog, submitted to clinical follow-up and chemotherapy. Case: A nine-year old male mixed-breed dog was presented due to the observation of an increased left mandibular lymph node. The previous cytological examination was suggestive of reactive hyperplasia and histopathological examination, by incisional biopsy, compatible with lymphocytic low-grade lymphoma. Physical examination revealed enlarged and firm left mandibular lymph node and adequate physical condition.A cytological examination was performed in the mandibular and both popliteal lymph nodes and revealed many small lymphocytes with hyperchromatic chromatin, rarely evident nucleolus and whose cytoplasm often projected in the form of a “hind-mirror” or “comet tail”, compatible with lymphocytic lymphoma (low grade) and suggestive of TZL, in the both lymph nodes. The histopathological and immunohistochemical examination, of the mandibular lymph node, were chosen to confirm the diagnosis. At histopathology it was observed 40% of the sample contained a monotonous cell population, composed by small lymphocytes, with some presenting “hand-mirror” morphology. Two mitotic figures were evidenced per field of high magnification (40x), inferring a low-grade disease. Immunohistochemical analysis revealed neoplastic proliferation with immunolabeling of CD3 lymphocytes and positivity for Ki-67, but negative for CD20, CD79a, CD45, MUM-1 and PAX-5. Although there is no consensus about requirements and treatment´s efficacy, it has been chosen to treat the dog with chlorambucil, because of the elevated Ki-67 value (48%). The patient obtained a free-progression interval higher than 820 days, from the earlier investigations of lymphadenopathy, with excellent quality of life and no side effects related to the use of chlorambucil. Discussion: Although TZL is a common subtype of lymphoproliferative disease in dog, it is still underdiagnosed. The TZL diagnosis can be suggested by cytology, from the disclosures in neoplastic cells of a cytoplasmic projections, recognized as a “hand-mirror” or “comet tail”, corroborated with the present case, however the histopathology is confirmatory. Immunohistochemistry in which the neoplasm cells showed a positive immunolabeling for CD3 and negative for CD79a, CD20, CD45, MUM1 and PAX5, as evidenced in this report, confirming the T-cell origin. According to the literature, lymphomas composed by small clear cells and cytoplasm projecting by cytology, immunolabeling CD3 and CD25 positive and CD45 negative are, together, findings that confirmed TZL. The biological behaviour of indolent lymphoma is still largely unknown, however the prognosis of dogs, with indolent lymphoma of T or B cells, seems to be favourable. Studies showed different days of median overall survival, such as 760 days and 4.4 years. In the present case, the dog showed 820 days, confirming the good prognosis and an indolent behavoiur. Aggressive chemotherapy protocols are not necessary for such cases and the treatment with chlorambucil, without the association of prednisolone, has been well tolerated by the patient, which showed no side effects until the moment.

Quality of life of patients with type 2 diabetes mellitus: A cross-sectional study

Background: Diabetes mellitus, a chronic noncommunicable disease, is associated with long-term damage of multiple organ system with its long-term complications and significantly impacts upon the quality of life (QoL) of affected patients. Methods: A survey was carried out on 245 patients during thirty sessions of diabetes outpatient department at multispecialty hospitals, among which 228 patients agreed for the participation. A final survey was carried on 200 patients, whereas 28 patients did not fit into the criteria. Further evaluation was carried out using the World Health Organization QoL-BREF questionnaire in Hindi, English, and Marathi versions. The mean score and total score of domains were calculated to check the QoL of the patients. Results: Almost 72% of the participants mentioned good QoL in physical domain with 18% mentioning average QoL. Around 35% mentioned excellent QoL in psychological domain with 46% mentioning good QoL. Around 55% mentioned good QoL in social domain. Majority of participants mentioned good (23%) to excellent (71%) QoL in environmental domain. The physical domain demonstrated a mean score of 66.6 ± 9.303 (min 44, max 94). The psychological domain demonstrated the mean score of 70.9, ±15.558, (min 5, max 94). The social domain demonstrated the mean score of 75.96, ±15.245, (min 31, max 100). The environmental domain demonstrated the mean score of 82.19, ±13.211, (min 31, max 100). Conclusion: Overall patients mentioned average-to-good QoL in physical, psychological, and social domain, and a majority of patients had good QoL in environmental domain.

Outcome, quality of life and direct costs after out-of-hospital cardiac arrest in an urban region of Switzerland

BackgroundConsidering the significant morbidity and mortality of out-of-hospital cardiac arrest, only little data on survival or quality of life after successful resuscitation is available in Europe. Additionally, economic aspects of such events are poorly studied. The purpose of this study is to provide data for survival, quality of life and costs directly related to the cardiac arrest for a region of Switzerland served by one emergency medical service (EMS).MethodsEighty eight patients older than 18 years of age that were resuscitated by the EMS Winterthur in the year 2013 were included and retrospective analysis of EMS-protocols was performed. For patients alive at follow-up, 2 years after the event, a structured interview with quality of life questionnaires was conducted. This study was accepted by the local Ethics Committee.ResultsThirty five percent (n = 31) of resuscitated patients were admitted alive to the hospital following out-of-hospital cardiac arrest. This incidence was as high as 60%, if the patients had a shockable rhythm as first rhythm. Survival to follow-up was 16% (n = 14). These patients had an excellent quality of life overall, with little to no limitations in daily life. There was no significant difference in survival for patients in outlying regions with comparatively longer timespans until arrival of EMS. Median EMS-costs for deceased patients were CHF 1731 (inter-quartile range 346), for survivors CHF 2′169 (inter-quartile range CHF 444) and median hospital-costs were CHF 27′707 (inter-quartile range CHF 62′783). ConclusionQuality of care for patients with out-of-hospital cardiac arrest in the region of Winterthur is high, including patients in outlying regions. The associated costs are similar to other European countries.Trial registrationThis trial was registered with www.clinicaltrials.gov under NCT02625883.