Publication date: Available online 24 August 2017
Source:Women and Birth
Author(s): Arndt Büssing, Undine Waßermann, Niels Christian Hvidt, Alfred Längler, Michael Thiel
BackgroundSpirituality is part of the basic needs of all humans, yet often undervalued by health professionals. Less is known about the spiritual needs of mothers of preterm or sick new born children.AimIdentify unmet psychosocial and spiritual needs of these mothers, and to relate these needs to their perceived stress and impairments of life concerns.MethodsAnonymous cross-sectional survey with standardized instruments (e.g., Spiritual Needs Questionnaire) among 125 mothers of two paediatric departments in Germany.FindingsMothers felt supported by their partner and hospital staff, and hospital staff assured 82% of them that they must not worry about their child's prognosis. They nevertheless did have specific unmet spiritual needs. Religious Needs and Existentialistic Needs scored lowest, while Giving/Generativity Needs were of moderate and Inner Peace Needs of strongest relevance. With respect to the expected diagnosis and prognosis of their child, there were no significant differences for their secular spiritual needs scores, but significant differences for Religious Needs which scored highest in mothers with children having an unclear prognosis (F=8.6; p=.004). Particularly Inner Peace Needs correlated with their stress perception (r=.34), impairments of life concerns (r=.25) and grief (r=.23).DiscussionMothers of sick born/premature children felt supported by the hospital team and their partner, but nevertheless experienced stress and daily life impairments, and particularly have unmet Inner Peace Needs.ConclusionsAddressing mothers' specific needs may help support them in their struggle with their difficult situation avoiding fears and insecurity and thus facilitating positive bonding to their child.
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Πέμπτη 24 Αυγούστου 2017
Spiritual needs of mothers with sick new born or premature infants—A cross sectional survey among German mothers
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DOI: 10.1055/s-0043-117179
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© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Therapeutic antibodies against cancer stem cells: a promising approach
Abstract
Monoclonal antibodies have been extensively used to treat malignancy along with routine chemotherapeutic drugs. Chemotherapy for metastatic cancer has not been successful in securing long-term remission of disease. This is in part due to the resistance of cancer cells to drugs. One aspect of the drug resistance is the inability of conventional drugs to eliminate cancer stem cells (CSCs) which often constitute less than 1–2% of the whole tumor. In some tumor types, it is possible to identify these cells using surface markers. Monoclonal antibodies targeting these CSCs are an attractive option for a new therapeutic approach. Although administering antibodies has not been effective, when combined with chemotherapy they have proved synergistic. This review highlights the potential of improving treatment efficacy using functional antibodies against CSCs, which could be combined with chemotherapy in the future.
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Can the performance of a quantitative FIT-based colorectal cancer screening programme be enhanced by lowering the threshold and increasing the interval?
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Therapeutic antibodies against cancer stem cells: a promising approach
Abstract
Monoclonal antibodies have been extensively used to treat malignancy along with routine chemotherapeutic drugs. Chemotherapy for metastatic cancer has not been successful in securing long-term remission of disease. This is in part due to the resistance of cancer cells to drugs. One aspect of the drug resistance is the inability of conventional drugs to eliminate cancer stem cells (CSCs) which often constitute less than 1–2% of the whole tumor. In some tumor types, it is possible to identify these cells using surface markers. Monoclonal antibodies targeting these CSCs are an attractive option for a new therapeutic approach. Although administering antibodies has not been effective, when combined with chemotherapy they have proved synergistic. This review highlights the potential of improving treatment efficacy using functional antibodies against CSCs, which could be combined with chemotherapy in the future.
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Quantitative Single-Photon Emission Computed Tomography/Computed Tomography for Glomerular Filtration Rate Measurement
Abstract
Purpose
We propose a quantitative Tc-99m diethylenetriaminepentaacetic acid (DTPA) single-photon emission computed tomography/computed tomography (SPECT/CT) for glomerular filtration rate (GFR) measurement.
Methods
Quantitative SPECT/CT data obtained at 2–3 min post-Tc-99m DTPA injection (370 MBq) were used to determine % injected doses (%IDs) for individual kidneys. The reproducibility of %ID measurement was tested and compared with planar scintigraphy. Cr-51 ethylenediaminetetraacetic acid (EDTA) GFR was used as reference standard. Nine young volunteers, representing normal GFR, and ten older volunteers, reflecting impaired GFR, were enrolled. The established GFR equation derived from these volunteers was applied to 19 renal tumor patients post-partial nephrectomy.
Results
At 2−3 min, %ID was most reproducible with the highest intraclass correlation (ICC) (0.9379) and lowest % coefficient of variation (CV) (6.5259%), which were more reliable than the ICC (0.9368) and %CV (6.7689%) of planar scintigraphy. Cr-51 EDTA GFR (93.16 ± 24.81 ml/min) correlated significantly with %ID (7.66 ± 2.15%, r = 0.7906, p = 0.0001), yielding an equation: Cr-51 EDTA GFR (ml/min) = (%ID × 9.1462) + 23.0653. This equation revealed significant decreases in total and nephrectomized kidney GFR (p = 0.0012 and p < 0.0001, respectively) from preoperative to 3-month postoperative measurements.
Conclusions
Quantitative Tc-99m DTPA SPECT/CT produces reliable and clinically applicable %ID estimates that translate to the GFR of individual kidneys.
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Renal NUT carcinoma: A case report
Nuclear protein in testis (NUT)-midline carcinomas were first described more than two decades ago with characteristic reciprocal translocations involving BRD4 on chromosomes 15 and NUTM1 on chromosome 19 (1). Over the years, these tumors have been reported in non-midline locations as well as outside of the upper aerodigestive tract and mediastinum. We recently encountered a renal NUT carcinoma (NC) diagnosed next generation sequencing (NGS) that is reported here.
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PNL2: An Adjunctive Biomarker for Renal Angiomyolipomas and PEComas
Abstract
Aims
Renal angiomyolipoma (AML) and perivascular epithelioid cell tumor (PEComa) are members of the microphthalmia-associated transcription factor (MiTF) family of tumors. Traditionally, HMB45 and MelanA have been used to diagnose these lesions; however, low sensitivity can render interpretation difficult. PNL2 is a sensitive and specific biomarker for epithelioid melanoma, and immunoreactivity has also been shown in small series of PEComas. This study determined the utility of PNL2 in MiTF and non-MiTF renal tumors.
Methods and Results
PNL2 immunostaining was performed on 196 tumors, including 40 MiTF renal tumors (AMLs, epithelioid AMLs, sclerosing PEComas, malignant PEComas, and Xp11.2 renal cell carcinomas (RCCs)) and 156 non-MiTF renal tumors. HMB45, MelanA and CathepsinK were also evaluated in a subset of MiTF tumors. Overall, 85% of AMLs and PEComas were positive for PNL2, compared to 81%, 76%, and 95% with HMB45, MelanA, and Cathepsin K, respectively. In 55% of cases, PNL2 stained more extensively when compared to HMB45. PNL2 staining was greater in sclerosing and malignant PEComas (89%) when compared to HMB45 (78%) and MelanA (38%). All remaining renal tumors, except 1 melanocytic Xp11.2 RCC, were negative for PNL2.
Conclusions
NL2 has relatively high sensitivity and specificity for AML and PEComas when compared to non-MiTF renal tumors, and PNL2 appears to be a more useful biomarker for sclerosing and malignant PEComas. For cases that are limited in tissue quantity (i.e., core biopsies) and/or are morphologically suspicious for AML/PEComa, but negative or focally positive for HMB45 and MelanA, PNL2 may be a useful adjunct biomarker.
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Spinal deformity changes in children with long-term vertical expandable prosthetic titanium rib (VEPTR) treatment
Publication date: Available online 24 August 2017
Source:The Spine Journal
Author(s): Andrea S. Gantner, Lena Braunschweig, Konstantinos Tsaknakis, Heiko M. Lorenz, Anna K. Hell
Background ContextIn several studies, vertical expandable prosthetic titanium rib (VEPTR) implants have shown good scoliosis control in children with the longest reported follow-up (f/u) of 3.6 years. For growing rods, recent studies suggest a decreased efficiency of correction starting just after that time. To our knowledge, no long-term results of children with VEPTR treatment are available.PurposeTo evaluate spinal deformity in scoliotic children and to investigate correction potential of VEPTR implants at several time points of treatment, particularly after long-term f/u.Study Design/SettingRetrospective case series of 32 children with spinal deformity and VEPTR treatment with analysis of clinical and radiological data pre and post VEPTR implantation and every two years during the f/u period.Patient sample32 patients with spinal deformity and VEPTR treatment.Outcome measuresPatients had a primary VEPTR implantation due to spinal deformity and thoracic insufficiency syndrome and repeated lengthening procedures every six months. Clinical data were assessed and radiological parameters were analyzed. The main thoracic scoliotic curve and associated curves as well as kyphosis, lordosis, pelvic obliquity and spinal length were measured in all radiographs until the end of VEPTR treatment or the last available examination.MethodsDevelopment of the different parameters during f/u was evaluated and statistical analysis was performed with Statistica version 13.0. No funding was obtained for this study. The authors have no conflicts of interest to declare.ResultsDirectly after VEPTR implantation, thoracic and lumbar curves corrected significantly, were stable at 2.8 year f/u and increased at 5.5 year f/u, whereas cervical scoliosis was not affected by the treatment. The sagittal profile was initially improved both in kyphosis and lordosis. However, at 5.5 year f/u hyperkyphosis had deteriorated beyond the initial deformity. Pelvic obliquity was significantly restored especially in neuromuscular patients and increasing spinal length was achieved within the 5.5 year f/u.ConclusionIn children with spinal deformity, implantation of the VEPTR device sufficiently corrected the deformity in all planes. During long-term f/u scoliosis increased slightly and was rather well controlled, whereas the implant system was not able to prevent deterioration of hyperkyphosis. Pelvic obliquity was well balanced and spinal lengthening was achieved during long-term f/u.
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Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1
Xue and colleagues show that prostaglandin E1 (PGE1) inhibits the activity and self-renewal of human CML leukemic stem cells. Combination of PGE1 or an agonist for its receptor EP4 with conventional tyrosine kinase inhibitor treatment can effectively target CML leukemic stem cells and reduce leukemia growth.
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Phenolic Glycolipid Facilitates Mycobacterial Escape from Microbicidal Tissue-Resident Macrophages
Cambier et al. find that activation of the STING pathway in lung-resident microbicidal macrophages by the mycobacterial surface lipid PGL enables bacterial escape by inducing the recruitment of mycobacterium-permissive monocytes via the CCL2-CCR2 chemokine axis. Their findings reveal a relocation strategy that enables mycobacterial dissemination, and argue for the potential of interventions targeting PGL in the prevention of tuberculosis.
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Ablation of the Cβ2 subunit of PKA in immune cells leads to increased susceptibility to systemic inflammation in mice
Protein kinase A (PKA) is a holoenzyme composed of a regulatory subunit dimer and two catalytic subunits and regulates numerous cellular functions including immune cell activity. There are two major catalytic subunit genes, PRKACA and PRKACB encoding the catalytic subunits Cα and Cβ. The PRKACB gene encodes several splice variants including Cβ2, which is enriched in T-, B- and natural killer cells. Cβ2 is significantly larger (46 kDa) than any other C splice variant. In this study we characterized mice ablated for the Cβ2 protein demonstrating a significantly reduced cAMP-induced catalytic activity of PKA in the spleenocytes, lymphocytes and thymocytes. We also observed a significantly increased number of CD62L-expressing CD4+ and CD8+ T cells in LNs, accompanied by increased susceptibility to systemic inflammation by the Cβ2 ablated mice. The latter was reflected in an elevated sensitivity to collagen-induced arthritis (CIA), as well as higher concentration of TNF-α and lower concentration of IL-10 in response to LPS challenges. We suggest a role of Cβ2 in regulating innate as well as adaptive immune sensitivity in vivo.
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Does antithrombotic therapy improve survival with colorectal cancer?
Abstract
Background
The study aimed to evaluate the prognosis for patients with colorectal cancer who underwent surgery while receiving antithrombotic therapy (ATT) across all disease stages and for patients at disease stages 0–III.
Methods
This retrospective cohort study included 710 Japanese patients who underwent surgery for colorectal cancer between January 2009 and November 2015 at our institution. Approximately 35% of these patients received ATT. Of these, 199 (28.0%) received antiplatelet therapy, and 76 (10.7%) received anticoagulant therapy. We investigated the prognosis among patients with colorectal cancer receiving ATT, antiplatelet therapy, or anticoagulant therapy in all-stage and stage 0–III cancers.
Results
For all disease stages combined, no benefit was observed for ATT, antiplatelet therapy, and anticoagulant therapy groups in the overall survival rates (ATT: 87.8 vs. 78.4%, P = 0.23; antiplatelet therapy: 87.8 vs. 78.6%, P = 0.25; and anticoagulant therapy: 92.2 vs. 80.2%, P = 0.26). However, overall survival rates of patients with stage 0–III colorectal cancer undergoing ATT, antiplatelet therapy, and anticoagulant therapy significantly improved. (ATT: 98.5 vs. 92.7%, P = 0.01; antiplatelet therapy: 98.3 vs. 91.1%, P = 0.02; and anticoagulant therapy: 100 vs. 92.1%, P = 0.00).
Conclusion
Receiving ATT significantly improves overall survival rates in patients with stage 0–III colorectal cancer.
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Modeling DNA damage-induced pneumopathy in mice: insight from danger signaling cascades
Abstract
Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secretory program. The resulting pro-inflammatory and pro-angiogenic microenvironment triggers a cascade of events that can lead within weeks to a pronounced lung inflammation (pneumonitis) or after months to excessive deposition of extracellular matrix molecules and tissue scarring (pulmonary fibrosis).
The use of preclinical in vivo models of DNA damage-induced pneumopathy in genetically modified mice has helped to substantially advance our understanding of molecular mechanisms and signalling molecules that participate in the pathogenesis of radiation-induced adverse late effects in the lung. Herein, murine models of whole thorax irradiation or hemithorax irradiation nicely reproduce the pathogenesis of the human disease with respect to the time course and the clinical symptoms. Alternatively, treatment with the radiomimetic DNA damaging chemotherapeutic drug Bleomycin (BLM) has frequently been used as a surrogate model of radiation-induced lung disease. The advantage of the BLM model is that the symptoms of pneumonitis and fibrosis develop within 1 month.
Here we summarize and discuss published data about the role of danger signalling in the response of the lung tissue to DNA damage and its cross-talk with the innate and adaptive immune systems obtained in preclinical studies using immune-deficient inbred mouse strains and genetically modified mice. Interestingly we observed differences in the role of molecules involved in damage sensing (TOLL-like receptors), damage signalling (MyD88) and immune regulation (cytokines, CD73, lymphocytes) for the pathogenesis and progression of DNA damage-induced pneumopathy between the models of pneumopathy induced by whole thorax irradiation or treatment with the radiomimetic drug BLM. These findings underline the importance to pursue studies in the radiation model(s) if we are to unravel the mechanisms driving radiation-induced adverse late effects.
A better understanding of the cross-talk of danger perception and signalling with immune activation and repair mechanisms may allow a modulation of these processes to prevent or treat radiation-induced adverse effects. Vice-versa an improved knowledge of the normal tissue response to injury is also particularly important in view of the increasing interest in combining radiotherapy with immune checkpoint blockade or immunotherapies to avoid exacerbation of radiation-induced normal tissue toxicity.
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Core-needle biopsy of breast cancer is associated with a higher rate of distant metastases 5 to 15 years after diagnosis than FNA biopsy
BACKGROUND
The literature offers discordant results regarding whether diagnostic biopsy is associated with the dissemination of cancer cells, resulting in local and/or distant metastasis. The long-term outcomes of patients with breast cancer were compared between those who were diagnosed using either fine-needle aspiration biopsy (FNAB) or core-needle biopsy (CNB) during 2 decades: the 1970s and 1990s.
METHODS
In the 1970s, the only diagnostic needle biopsy method used for breast cancer in Sweden was FNAB. CNB was introduced 1989 and became established in Stockholm Gotland County in the early 1990s. The authors compared the clinical outcomes of patients diagnosed using FNAB from 1971 to 1976 (n = 354) versus those of patients diagnosed using CNB from 1991 to 1995 (n = 1729). Adjusting for differences in various treatment modalities, mammography screening, tumor size, DNA ploidy, and patient age between the 2 decades, 2 strictly matched samples representing FNAB (n = 181) and CNB (n = 203) were selected for a 15-year follow-up study.
RESULTS
In a comparison of the rates of distant metastasis in the strictly matched patient groups from the FNAB and CNB cohorts, significantly higher rates of late-appearing (5-15 years after diagnosis) distant metastasis were observed among the patients who were diagnosed on CNB compared with those who were diagnosed on FNAB. No significant difference in local metastasis was observed between the 2 groups.
CONCLUSIONS
At 5 to 15 years after diagnosis of the primary tumor, CNB-diagnosed patients had significantly higher rates of distant metastases than FNAB-diagnosed patients. [See related editorial on pages 000-000, this issue.] Cancer Cytopathol 2017. © 2017 American Cancer Society.
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Primum Non Nocere
In a 15-year follow-up study based on the presence and numbers of circulating tumor cells and tumor DNA before, immediately after, and at defined points after core-needle and fine-needle biopsy procedures, a strong case is made for revisiting and potentially changing current practice to include fine-needle biopsy as the initial biopsy procedure in patients with breast masses. See also pages 000-000.
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Diagnostic and prognostic role of urinary collagens in primary human bladder cancer
Abstract
Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of CYFRA21-1, NMP-22, and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21-1, and NMP-22 in urine supernatants were measured using enzyme-linked immunosorbent assays. The diagnostic performance and optimal cutoff values were determined by receiver operating characteristic analysis. Urine levels of COL4A1, COL13A1, the combined values of COL4A1 and COL13A1 (COL4A1+COL13A1), and CYFRA21-1 were significantly elevated in urine from patients with BCa compared to the controls. Among these biomarkers, the optimal cutoff value of COL4A1+COL13A1 at 1.33 ng/mL resulted in 57.4%, 83.7%, 56.1%, 80.7%, and 91.7% sensitivity for low-grade tumors, high-grade tumors, Ta, T1, and muscle invasive disease, respectively. We evaluated the prognostic value of preoperative urine levels in 130 non-muscle invasive BCa samples after the initial transurethral surgery. A high urinary COL4A1+COL13A1 was found to be an independent risk factor of intravesical recurrence. Although these data need to be externally validated, urinary COL4A1 and COL13A1 could be a potential diagnostic and prognostic biomarker for BCa. This easy-to-use urinary signature identifies a subgroup of patients with high probability of recurrence and progression in non-muscle invasive and muscle invasive BCa.
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CBX8 is a predictor of muscle invasive bladder cancer and promotes cell proliferation by repressing the p53 pathway
Abstract
CBX8, also known as human polycomb 3, is a repressor that maintains the transcriptionally repressive state in various cellular genes, and has been reported to promote tumorigenesis. In the present study we examined the CBX8 expression in 8 pairs of muscle invasive bladder cancer tissues and adjacent non-tumor tissues, and found that CBX8 was frequently upregulated in muscle invasive bladder cancer tissues when compared to adjacent non-tumor tissues. Analysis showed that high expression of CBX8 in 152 muscle invasive bladder cancer specimens was associated with progression of the T-, N-, and M stage (P = 0.004, 0.005, <0.001, respectively). Furthermore, Kaplan-Meier survival analysis and log-rank test showed that muscle invasive bladder cancer patients with high CBX8 expression had a poor rate of overall survival (P <0.001) and 5-year recurrence-free survival (P <0.001) compared to patients with low CBX8 expression. High CBX8 expression predicted poor overall survival and 5-year recurrence-free survival in T- and N- stages of muscle invasive bladder cancer patients. Moreover, knockdown of CBX8 inhibited cells proliferation of urothelial carcinoma of the bladder both in vitro and in vivo. In addition, CBX8 depletion resulted in cell cycle delay of urothelial carcinoma cells of the bladder at the G2/M phase via the p53 pathway. The data suggests that high expression of CBX8 plays a critical oncogenic role in aggressiveness of urothelial carcinoma cells of the bladder through promoting cancer cell proliferation by repressing the p53 pathway, and CBX8 could be employed as a novel predictor for muscle invasive bladder cancer patients.
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Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3
Abstract
In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron-dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOXs) to ferroptosis in oncogenic Ras-expressing cancer cells. Several 12/15-LOX inhibitors prevented cell death induced by erastin and RSL3. Furthermore, siRNA-mediated silencing of ALOX15 significantly decreased both erastin- and RSL3-induced ferroptotic cell death, whereas exogenous overexpression of ALOX15 enhanced the effect of these compounds. Immunofluorescence analyses revealed that the ALOX15 protein consistently localizes to cell membrane during the course of ferroptosis. Importantly, treatments of cells with ALOX15-activating compounds accelerated cell death at low, but not high doses of erastin and RSL3. These observations suggest that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes.
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Elevated expression of JAM-A promotes neoplastic properties of lung adenocarcinoma
Abstract
A cell-cell adhesion protein, junctional adhesion molecule-A (JAM-A), has been shown to be involved in neoplasia of various organs. However, the fundamental role of JAM-A in tumorigenesis is still controversial because dysregulated expression of this protein has distinct effects, playing opposite roles in carcinogenesis depending on the target tissues. In the present study, we found elevated levels of JAM-A expression in lung adenocarcinoma and its preinvasive lesions, including atypical adenomatous hyperplasia and adenocarcinoma in situ by immunohistochemistry. We also showed that suppression of constitutive JAM-A expression conferred target cells with increased susceptibility to apoptosis in lung adenocarcinoma cells. Consequently, inhibition of JAM-A activity decreased colony-forming capability in vitro and tumorigenicity in vivo. The transformed phenotype following suppression of JAM-A expression was sufficient to reduce motile and invasive capacities. Importantly, knockout of JAM-A had striking effects on cells. Our observations suggested that increased expression of JAM-A promotes neoplasia of lung adenocarcinoma. In addition, an anti-JAM-A antibody efficiently reduced cell proliferation and provoked apoptosis, indicating the potential feasibility of JAM-A-inhibitory cancer therapy.
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A phase 1 study of veliparib with carboplatin and weekly paclitaxel in Japanese patients with newly diagnosed ovarian cancer
Abstract
This phase 1, open-label, dose-escalation study was conducted to determine the safety, tolerability, pharmacokinetics, and preliminary efficacy of veliparib with carboplatin and weekly paclitaxel in Japanese women with newly diagnosed, advanced ovarian cancer. Patients received veliparib at 100 or 150 mg twice daily on days 1–21 with carboplatin (area under the concentration–time curve 6 mg/mL•min) on day 1 and paclitaxel 80 mg/m2 on days 1, 8, and 15 every 3 weeks for up to 6 21-day cycles. Dose escalation followed a 3+3 design to determine dose-limiting toxicities, maximum tolerated dose, and the recommended phase 2 dose. Nine patients (median age 62 [range 27–72] years) received a median of 5 (range 3–6) cycles of treatment (3 at 100 mg, 6 at 150 mg). There were no dose-limiting toxicities. The most common adverse events of any grade were neutropenia (100%), alopecia (89%), peripheral sensory neuropathy (78%), and anemia, nausea, and malaise (67% each). Grade 3 or 4 adverse events were associated with myelosuppression. Pharmacokinetics of carboplatin/paclitaxel were similar at both veliparib doses. Response, assessed in 5 patients, was partial in 4 and complete in 1 (objective response rate 100%). Response could not be assessed in 4 patients who had no measurable disease at baseline. The recommended phase 2 dose of veliparib, when combined with carboplatin/paclitaxel, is 150 mg twice daily. Findings from this phase 1 trial demonstrate the tolerability and safety of veliparib with carboplatin/paclitaxel, a regimen with potential clinical benefit in Japanese women with ovarian cancer.
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c-Jun N-terminal kinase in pancreatic tumor stroma augments tumor development in mice
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease, and there is an urgent need to develop improved therapeutic approaches. The role of c-Jun N-terminal kinase (JNK) in PDAC stroma is not well defined even though dense desmoplastic reactions are characteristic of PDAC histology. We aimed to explore the role of JNK in PDAC stroma in mice. We crossed Ptf1aCre/+;KrasG12D/+ mice with JNK1-/- mice to generate Ptf1aCre/+;KrasG12D/+;JNK1-/- (Kras;JNK1-/-) mice. The tumor weight were significantly lower in Kras;JNK1-/- mice than in Kras;JNK1+/- mice, whereas histopathological features were similar. We also transplanted a murine PDAC cell line (mPC) with intact JNK1 subcutaneously into wild-type (WT) and JNK1-/- mice. The tumor diameters were significantly smaller in JNK1-/- mice. Phosphorylated JNK (p-JNK) was activated in α-SMA-positive cells in the tumor stroma, and mPC-conditioned medium activated p-JNK in tumor-associated fibroblasts (TAFs) in vitro. The relative expression of Ccl20 was downregulated in stimulated TAFs. Ccl20 is an important chemokine that promotes CD8+ T-cell infiltration via recruitment of dendritic cells, and the number of CD8+ T cells was decreased in Kras;JNK1+/- mice compared with Kras;JNK1-/- mice. These results suggest that the cancer secretome decreases Ccl20 secretion from TAFs via activation of JNK, and downregulation of Ccl20 secretion might be correlated with reduction of infiltrating CD8+ T cells. Therefore, we concluded that inhibition of activated JNK in pancreatic tumor stroma could be a potential therapeutic target to increase Ccl20 secretion from TAFs and induce accumulation of CD8+ T cells, which would be expected to enhance antitumor immunity.
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Persistent detection of dengue virus RNA in vaginal secretion of a woman returning from Sri Lanka to Italy, April 2017
We describe the dynamics of dengue virus (DENV) infection in a woman in her mid-30s who developed fever after returning from Sri Lanka to Italy in April 2017. Laboratory testing demonstrated detectable DENV-RNA in plasma, urine, saliva, vaginal secretion. Persistent shedding of DENV-RNA was demonstrated in vaginal secretion, and DENV-RNA was detectable in the pelleted fraction up to 18 days from symptom onset. These findings give new insights into DENV vaginal shedding and vertical transmission.
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The effectiveness of influenza vaccination in preventing hospitalisations of elderly individuals in two influenza seasons: a multicentre case-control study, Spain, 2013/14 and 2014/15
Influenza vaccination may limit the impact of influenza in the community. The aim of this study was to assess the effectiveness of influenza vaccination in preventing hospitalisation in individuals aged???65 years in Spain. A multicentre case-control study was conducted in 20 Spanish hospitals during 2013/14 and 2014/15. Patients aged???65 years who were hospitalised with laboratory-confirmed influenza were matched with controls according to sex, age and date of hospitalisation. Adjusted vaccine effectiveness (VE) was calculated by multivariate conditional logistic regression. A total of 728 cases and 1,826 matched controls were included in the study. Overall VE was 36% (95% confidence interval (CI): 22-47). VE was 51% (95% CI: 15-71) in patients without high-risk medical conditions and 30% (95% CI: 14-44) in patients with them. VE was 39% (95% CI: 20-53) in patients aged 65-79 years and 34% (95% CI: 11-51) in patients aged???80 years, and was greater against the influenza A(H1N1)pdm09 subtype than the A(H3N2) subtype. Influenza vaccination was effective in preventing hospitalisations of elderly individuals.
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Large measles outbreak introduced by asylum seekers and spread among the insufficiently vaccinated resident population, Berlin, October 2014 to August 2015
The largest measles outbreak in Berlin since 2001 occurred from October 2014 to August 2015. Overall, 1,344 cases were ascertained, 86% (with available information) unvaccinated, including 146 (12%) asylum seekers. Median age was 17 years (interquartile range: 4-29 years), 26% were hospitalised and a 1-year-old child died. Measles virus genotyping uniformly revealed the variant 'D8-Rostov-Don' and descendants. The virus was likely introduced by and initially spread among asylum seekers before affecting Berlin's resident population. Among Berlin residents, the highest incidence was in children aged?<?2 years, yet most cases (52%) were adults. Post-exposure vaccinations in homes for asylum seekers, not always conducted, occurred later (median: 7.5 days) than the recommended 72 hours after onset of the first case and reached only half of potential contacts. Asylum seekers should not only have non-discriminatory, equitable access to vaccination, they also need to be offered measles vaccination in a timely fashion, i.e. immediately upon arrival in the receiving country. Supplementary immunisation activities targeting the resident population, particularly adults, are urgently needed in Berlin.
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Glycemic effects of quinine infusion in healthy volunteers
We aimed to quantify the glycemic effects of quinine in healthy individuals.
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Tanzania to use drone network to deliver critical medicines
In 2018, they will begin using drones to make up to 2,000 deliveries per day to more than 1,000 health facilities
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6-year-old pulls drowning toddler twin cousins from pool
The twins' father, a first responder, said they were limp and "blue as a pair of blue jeans" when he began CPR
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Concurrent chemoradiotherapy with or without cetuximab for stage II to IVb nasopharyngeal carcinoma: a case–control study
Abstract
Background
This study aimed to evaluate the long-term outcome and toxicities in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by concurrent chemoradiotherapy (CCRT) with/without adding cetuximab.
Methods
A total of 62 patients treated with CCRT plus cetuximab were matched with 124 patients treated with CCRT alone by age, sex, pathological type, T category, N category, disease stage, radiotherapy (RT) technique, Epstein-Barr virus (EBV) DNA levels, and Eastern Cooperative Oncology Group (ECOG). Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan–Meier method and log-rank test. Treatment toxicities were clarified and compared between two groups.
Results
A total of 186 well-balanced stage II to IV NPC patients were retrospectively analyzed (median follow-up, 76 months). Compared to CCRT alone, adding cetuximab resulted in more grade 3 to 4 radiation mucositis (51.6% vs. 23.4%; P < 0.001). No differences were found between the CCRT + cetuximab group and the CCRT group in 5-year OS (89.7% vs. 90.7%, P = 0.386), 3-year PFS (83.9% vs. 88.7%, P = 0.115), the 3-year LRFS (95.0% vs. 96.7%, P = 0.695), and the 3-year DMFS (88.4% vs 91.9%, P = 0.068). Advanced disease stage was the independent prognostic factor predicting poorer OS and PFS.
Conclusion
Adding cetuximab to CCRT did not significantly improve benefits in survival in stage II to IV NPC and exacerbated acute mucositis and acneiform rash. Further investigations are warranted.
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Country and regional variations in purchase prices for essential cancer medications
Abstract
Background
Accessibility to essential cancer medications in low- and middle-income countries is threatened by insufficient availability and affordability. The objective of this study is to characterize variation in transactional prices for essential cancer medications across geographies, medication type, and time.
Methods
Drug purchase prices for 19 national and international buyers (representing 29 total countries) between 2010 and 2014 were obtained from Management Sciences for Health. Median values for drug pricing were computed, to address outliers in the data. For comparing purchase prices across geographic units, medications, and over time; Mann-Whitney U tests were used to compare two groups, Kruskal Wallis H tests were used to compare more than two groups, and linear regression was used to compare across continuous independent variables.
Results
During the five-year data period examined, the median price paid for a package of essential cancer medication was $12.63. No significant differences in prices were found based on country-level wealth, country-level disease burden, drug formulation, or year when medication was purchased. Statistical tests found significant differences in prices paid across countries, regions, individual medications, and medication categories. Specifically, countries in the Africa region appeared to pay more for a package of essential cancer medication than countries in the Latin America region, and cancer medications tended to be more expensive than anti-infective medications and cardiovascular medications.
Conclusions
Though preliminary, our study found evidence of variation in prices paid by health systems to acquire essential cancer medications. Primarily, variations in pricing based on geographic location and cancer medication type (including when comparing to essential medicines that treat cardiovascular and infectious diseases) indicate that these factors may impact availability, affordability and access to essential cancer drugs. These factors should be taken into consideration when countries assess formulary decisions, negotiate drug procurement terms, and when formulating health and cancer policy.
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Plain radiography in patients treated with intrathecal drug delivery using an implantable pump device
Abstract
Objectives
Intrathecal drug administration using an implanted pump system is well established in intractable spasticity and pain. However, despite continuous advancements in manufacturing technology, adverse events related to the pump and catheter still occur. Most of them, such as migration, damage, disconnection and occlusion, are related to the spinal catheter. The aim of this overview is to update radiologists on how plain radiography of the implanted delivery system for intrathecal drug administration should be interpreted and to increase awareness for the need of urgent and timely multidisciplinary troubleshooting.
Methods
Plain radiographic images of patients treated with intrathecal drug administration using an implantable drug delivery system were analysed in a multidisciplinary setting at our (university) referral centre for complications in intrathecal drug administration.
Results
Examples of catheter-related adverse events are described and a proposal is made for stepwise interpretation of standard plain radiographic images.
Conclusions
Plain radiological images are the mainstay for the diagnosis of catheter-related adverse events in intrathecal drug delivery. Radiologists play an important role in an early diagnosis. An awareness of abnormal radiological findings seems important to avoid a life-threatening withdrawal syndrome.
Teaching points
• Untimely cessation of intrathecal drug delivery can lead to a life-threatening withdrawal syndrome.
• Initially mild symptoms can lead to an exacerbation of a withdrawal syndrome.
• Most intrathecal catheter-related problems are visible on plain radiography.
• Common causes of catheter problems are migration, lacerations, occlusion and disconnection.
• Knowledge on implanted intrathecal catheters is crucial for interpretation of plain radiography.
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Compound Danshen Dripping Pill for Treating Nonproliferative Diabetic Retinopathy: A Meta-Analysis of 13 Randomized Controlled Trials
Objective. We assess the clinical effect of compound Danshen dripping pill (CDDP) for treating diabetic retinopathy (DR). Methods. Electronic databases were searched from January 2001 to October 2016 to locate randomized controlled trials (RCTs). Efficacy was measured as main outcome and microaneurysms, hemorrhage, exudate, vision, and fundus fluorescein angiography (FFA) were measured as second outcomes. Methodological quality for each study was evaluated, RevMan 5 software was used to assess treatment effects, and GRADE was used to rate quality of evidence. Results. We located 13 RCTs and methodological quality was evaluated as high risk. Statistics indicated CDDP for treating DR was better than controls and DR risk was reduced 64% with CDDP (RR: 0.36, ); retinal microaneurysms (MD = −4.32NO, ); retinal hemorrhages (MD = −0.70PD, ); exudate improvements (MD = −0.09PD, ); visual changes (MD = −0.12 letter, ); FFA (RR: 0.40, ). About GRADE, quality of evidence was "low." Conclusion. CDDP may be safe and efficacious for treating or delaying DR and may improve vision or delay vision loss.
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Chinese Classical Formula Sijunzi Decoction and Chronic Atrophic Gastritis: Evidence for Treatment Approach?
Objective. This aim is to evaluate the effect of Sijunzi decoction (SJZD) treating chronic atrophic gastritis (CAG). Methods. We performed searches in seven databases. The randomized controlled trials (RCTs) comparing SJZD with standard medical care or inactive intervention for CAG were enrolled. Combined therapy of SJZD plus conventional therapies compared with conventional therapies alone was also retrieved. The primary outcome included the incidence of gastric cancer and the improvement of atrophy, intestinal metaplasia, and dysplasia based on the gastroscopy and pathology. The secondary outcomes were Helicobacter pylori clearance rate, quality of life, and adverse event/adverse drug reaction. Results. Six RCTs met the inclusion criteria. The research quality was low in the trials. For the overall effect rate, pooled analysis from 4 trials showed that modified SJZD plus conventional medications exhibited a significant improvement (OR = 4.86; 95% CI: 2.80 to 8.44; P
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Prevalence and Correlates of Complementary and Alternative Medicine Use among Patients with Lung Cancer: A Cross-Sectional Study in Beirut, Lebanon
Patients with lung cancer are increasingly seeking complementary and alternative medicine (CAM) to improve their physiological and psychological well-being. This study aimed to assess CAM use among lung cancer patients in Lebanon. Using a cross-sectional design, 150 lung cancer patients attending the Basile Cancer Institute at the American University of Beirut Medical Center were interviewed. Participants completed a questionnaire addressing sociodemographic characteristics, lung cancer condition, and use of CAM. The main outcome of interest was "use of any CAM therapy since diagnosis." Prevalence of CAM use was 41%. The most commonly used CAM modality among study participants was "dietary supplements/special foods." Results of the multiple logistic regression analyses showed that CAM use was positively associated with Lebanese nationality and paying for treatment out of pocket and was negatively associated with unemployment and having other chronic diseases. About 10% of patients used CAM on an alternative base, 58% did not disclose CAM use to their physician, and only 2% cited health professionals as influencing their choice of CAM. This study revealed a prevalent CAM use among lung cancer patients in Lebanon, with a marginal role for physicians in guiding this use. Promoting an open-communication and a patient-centered approach regarding CAM use is warranted.
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Association between Sedentary Behaviour and Physical, Cognitive, and Psychosocial Status among Older Adults in Assisted Living
Objective. Identification of the factors that influence sedentary behaviour in older adults is important for the design of appropriate intervention strategies. In this study, we determined the prevalence of sedentary behaviour and its association with physical, cognitive, and psychosocial status among older adults residing in Assisted Living (AL). Methods. Participants (, mean age = 86.7) from AL sites in British Columbia wore waist-mounted activity monitors for 7 consecutive days, after being assessed with the Timed Up and Go (TUG), Montreal Cognitive Assessment (MoCA), Short Geriatric Depression Scale (GDS), and Modified Fall Efficacy Scale (MFES). Results. On average, participants spent 87% of their waking hours in sedentary behaviour, which accumulated in 52 bouts per day with each bout lasting an average of 13 minutes. Increased sedentary behaviour associated significantly with scores on the TUG (, ) and MFES (, ), but not with the MoCA or GDS. Sedentary behaviour also associated with male gender, use of mobility aid, and multiple regression with increased age. Conclusion. We found that sedentary behaviour among older adults in AL associated with TUG scores and falls-related self-efficacy, which are modifiable targets for interventions to decrease sedentary behaviour in this population.
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Ptosis, miosis and cats
Horner's syndrome (HS) is caused by a disruption in the oculosympathetic pathway. Both congenital and acquired HS are unusual in children. Acquired HS can be caused by trauma, surgical intervention, tumours, vascular malformations or infection.
We describe the case of a 6-year-old boy who was brought to our emergency department with ptosis, miosis, painful cervical lymphadenopathy and a cat scratch on a hand. The diagnosis of a cat scratch disease was confirmed by serology. A full recovery was observed on antibiotic treatment and cervical lymphadenomegaly reduction 3 weeks later.
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Man versus Nature — Also Sprach Zarathustra and an End-of-Life House Call
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Global, Regional, and National Burden of Rheumatic Heart Disease, 1990–2015
Rheumatic heart disease is a sequela of acute rheumatic fever, which is usually a disease of poverty associated with overcrowding, poor sanitation, and other social determinants of poor health. The near elimination of acute rheumatic fever and reduction in the rates of rheumatic heart disease in…
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Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control
The most effective blood-pressure goals for treatment with antihypertensive medications are uncertain. Treating hypertension to standard systolic blood-pressure goals is cost-saving or cost-effective among patients at high risk for cardiovascular disease in the United States. However, until…
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Stretching the Scope — Becoming Frontline Addiction-Medicine Providers
On our infectious diseases (ID) consult service, we recently cared for Mr. C. a young man with Staphylococcus aureus tricuspid valve endocarditis, septic arthritis, and empyema that were consequences of his opioid use disorder (OUD). Several years earlier, he had started taking oxycodone at…
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Rheumatic Heart Disease — An Iceberg in Tropical Waters
Rheumatic heart disease ranks as one of the most serious cardiovascular scourges of the past century. As a result of improvements in living conditions and the introduction of penicillin, the disease was almost eradicated in the developed world by the 1980s. However, it remains a force to be…
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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