The effect of antipyretics on immune response and fever following receipt of inactivated influenza vaccine in young children

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Emmanuel B. Walter, Christoph P. Hornik, Lisa Grohskopf, Charles E. McGee, Christopher A. Todd, Oidda I. Museru, Lynn Harrington, Karen R. Broder
BackgroundAntipyretics reduce fever following childhood vaccinations; after inactivated influenza vaccine (IIV) they might ameliorate fever and thereby decrease febrile seizure risk, but also possibly blunt the immune response. We assessed the effect of antipyretics on immune responses and fever following IIV in children ages 6 through 47 months.MethodsOver the course of three seasons, one hundred forty-two children, receiving either a single or the first of 2 recommended doses of IIV, were randomized to receive either oral acetaminophen suspension (n = 59) or placebo (n = 59) (double-blinded) or ibuprofen (n = 24) (open-label) immediately following IIV and every 4–8 h thereafter for 24 h. Blood samples were obtained at enrollment and 4 weeks following the last recommended IIV dose. Responses to IIV were assessed by hemagglutination inhibition assay (HAI). Seroprotection was defined as an HAI titer ≥1:40 and seroconversion as a titer ≥1:40 if baseline titer <1:10 or four-fold rise if baseline titer ≥1:10. Participants were monitored for fever and other solicited symptoms on the day of and day following IIV.ResultsSignificant differences in seroconversion and post-vaccination seroprotection were not observed between children included in the different antipyretic groups and the placebo group for the vaccine antigens included in IIV over the course of the studies. Frequencies of solicited symptoms, including fever, were similar between treatment groups and the placebo group.ConclusionsSignificant blunting of the immune response was not observed when antipyretics were administered to young children receiving IIV. Studies with larger sample sizes are needed to definitively establish the effect of antipyretics on IIV immunogenicity.



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Enhancing the role of vaccines in combatting antimicrobial resistance

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Charles Clift, David M. Salisbury
Interest in addressing antimicrobial resistance (AMR) has grown recently but little effort has been made to consider how existing and new vaccines could impact on AMR. A 2017 Chatham House meeting considered the role of vaccines and how to demonstrate their value through their impact on AMR. Ways existing vaccines have reduced antibiotic prescribing and the prevalence of some resistant organisms were reviewed. Other new vaccines could have a similar impact. In gonorrhoea, where complete resistance has developed, vaccine may be the best option. Valuing the impact of vaccines on AMR was challenging: there were difficult methodological issues and a lack of data for modelling. A participant poll suggested priorities for accelerated vaccine development were tuberculosis, typhoid, influenza, RSV and gonorrhoea. More evidence is needed to convince policymakers but that vaccine development projects should be considered by funders on the same basis as those for new antibiotics or diagnostics.



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The M2 protein of live, attenuated influenza vaccine encodes a mutation that reduces replication in human nasal epithelial cells

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Nicholas Wohlgemuth, Yang Ye, Katherine J. Fenstermacher, Hsuan Liu, Andrew P. Lane, Andrew Pekosz
The influenza A virus components of the live, attenuated influenza vaccine (LAIV) encode the HA and NA gene segments from a circulating virus strain and the remaining gene segments from the cold-adapted master donor virus, A/Ann Arbor/6/1960 (H2N2). The master donor virus imparts at least three phenotypes: temperature-sensitivity (ts), attenuation (att), and cold-adaption (ca). The genetic loci responsible for the att and ts phenotypes of LAIV were mapped to PB1, PB2, and NP by reverse genetics experiments using immortalized cell lines. However, some in vivo studies have demonstrated that the M segment, which acquired an alanine (Ala) to serine (Ser) mutation at M2 position 86 during cold adaption – a mutation found in no other influenza A virus strain - contributes to the att phenotype. Prior studies have shown this region of the M2 cytoplasmic tail to be critical for influenza virus replication. Using reverse genetics, we demonstrate that certain amino acid substitutions at M2 positions 83 and 86 alter the replication of influenza A/Udorn/307/72 (H3N2). Importantly, substitution of a Ser at M2 position 86 reduces A/Udorn/307/72 replication in differentiated primary human nasal epithelial cell (hNECs) cultures, but does not considerably affect replication in MDCK cells. When a Ser was substituted for Ala at M2 86 in LAIV, the virus replicated to higher titers and with faster kinetics in hNEC cultures, implicating this amino acid change as contributing to LAIV attenuation. Increased replication also resulted in increased production of IFN-λ. These data indicate the LAIV associated Ser mutation at M2 position 86 contributes to the att phenotype and is associated with a differential regulation of interferon in LAIV infection.



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Association of antibodies to Plasmodium falciparum merozoite surface protein-4 with protection against clinical malaria

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Ronald Perraut, Marie-Louise Varela, Charlotte Joos, Babacar Diouf, Cheikh Sokhna, Babacar Mbengue, Adama Tall, Cheikh Loucoubar, Aissatou Touré, Odile Mercereau-Puijalon
Identification of parasite antigens targeted by immune effector mechanisms that confer protection against malaria is important for the design of a multi-component malaria vaccine. Here, the association of antibodies reacting with the Plasmodium falciparum merozoite surface protein-4 (MSP4) with protection against clinical malaria was investigated in a Senegalese community living in an area of moderate, seasonal malaria transmission. Blood samples were collected at the end of an 8-month long dry season without any recorded parasite transmission from 206 residents enrolled in a prospective follow-up study. Active daily clinical monitoring was implemented during the subsequent five months. Entomologic monitoring documented parasite transmission during the first three months of follow-up. Serum IgG levels were determined by ELISA against three MSP4 baculovirus-encoded recombinant protein constructs, namely the full-length MSP4p40, MSP4p30 devoid of a highly polymorphic sequence stretch and the conserved C-terminal EGF-containing MSP4p20, as well as against a merozoite crude extract. Community seroprevalence against all three constructs was quite high, the lowest being against MSP4p30. Seroprevalence and antibody levels against the three MSP4 constructs were age-dependent. IgG1 dominated the anti-MSP4p20 responses, while both IgG1 and IgG3 were observed against MSP4p40. Anti-MSP4 antibodies were associated with the antibody-dependent respiratory burst (ADRB) activity in a functional assay of merozoite phagocytosis by polymorphonuclear cells. Importantly, high antibody levels against each of the three MSP4 constructs at the end of the dry season were associated with reduced morbidity during the subsequent transmission season in an age-adjusted Poisson regression model (IRR = 0.65 [0.50–0.83], P<0.001 for responses over the median values). These data are consistent with a protective role for the naturally acquired anti-MSP4 antibodies and support further development of MSP4 as a candidate component of malaria vaccine.



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Episode of Kasabach-Merritt phenomenon following Japanese encephalitis vaccination: Case report

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Xiaojie Yue, Xiong Zhao, Yefeng Dai, Qiang Shu
Kasabach-Merritt phenomenon (KMP) is a rare potentially life-threatening consumptive coagulopathy characterized by thrombocytopenia and hypofibrinogenemia occurring associated with the vascular tumors kaposiform hemangioendothelioma (KHE) and tufted angioma (TA).A 10-month old male infant, diagnosed with KHE on his left leg, underwent a rapid increase of the lesion and severe thrombocytopenia, one day after the first dose of inactivated Japanese encephalitis (JE) vaccination. The episode of KMP was treated successfully by steroid.KMP is a rare complication of vaccination that physicians should be aware of. Giving up the following vaccination to provide the recurrence of KMP is not recommended.



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A behavioral economics approach to the failed HPV vaccination program in Japan

Publication date: Available online 15 November 2017
Source:Vaccine
Author(s): Asami Yagi, Yutaka Ueda, Tadashi Kimura




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Recruitment barriers for prophylactic vaccine trials: A study in Belgium

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Lauriane Harrington, Pierre Van Damme, Corinne Vandermeulen, Stéphanie Mali
Recruitment of volunteers is one of the main challenges in clinical trial management, and there is little information about recruitment barriers for preventative vaccine trials. We investigated both the recruitment barriers and recruitment strategies for preventive vaccine trials in Belgium. A 10 min survey was used as well as interviews of staff at all clinical trial sites in Belgium that regularly perform vaccine trials. We observed that there are successful recruitment strategies and few recruitment issues for trials involving healthy adults and those over 65 years old. However, challenges face the recruitment of paediatric populations, pregnant women, patients and the very elderly (over 85 years old). From these results, we identified three priority areas to increase recruitment for prophylactic vaccine trials in Belgium. These are: the lack of public knowledge about infectious diseases; the lack of resources of healthcare professionals to take part in clinical trials; and the burden to potential volunteers to take part in a trial. These were discussed with stakeholders and solutions were proposed.



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The effect of selected molecules influencing the detrimental host immune response on a course of rabies virus infection in a murine model

Publication date: Available online 15 November 2017
Source:Vaccine
Author(s): Marcin Smreczak, Anna Marzec, Anna Orłowska, Paweł Trębas, Michał Reichert, Anna Kycko, Penelopa Koraka, Ab Osterhaus, Jan Franciszek Żmudziński
Rabies is invariably fatal, when post-exposure prophylaxis is administered after the onset of clinical symptoms. In many countries, rabies awareness is very low and the availability of post-exposure prophylaxis, as recommended by WHO guidelines, is very limited or non-existent, probably as a consequence of high cost. Therefore, new concepts for rabies therapy are needed. Innate immune mechanisms involving the production of pro-inflammatory cytokines and chemokines, activated after rabies infection, are thought to be involved in the neuropathogenesis of rabies. These mechanisms can contribute to a detrimental host response to the rabies virus (RABV) infection. The use of inhibitors of cytokines/chemokines are supposed to extend the survival of a sick individual. Inhibitors of TNF-α, IL-6 and MAPKs were used in RABV inoculated mice to define their influence on the survival time of rabid mice. The study demonstrated that all inhibitors extended mice survival, but at different rates. A log-rank test confirmed the statistically significant survival of mice treated with TNF-α (p = .0087) and MAPKs inhibitors (p = .0024). A delay in the time of onset of rabies was also recorded, in mice given TNF-α and MAPKs inhibitors. The highest virus load was found in the spinal cord and the lowest in the cortex, regardless of the experimental group. Significant TNF-α (p ≤ .0001) and IL-6 (p ≤ .0001) gene upregulation was observed in mice, as a consequence of RABV infection. Regarding MAPKs pathways, there was significant upregulation of the caspase 3 (p = .012, p = .0026) and Mcl-1 (p = .0348, p = .0153) genes, whereas significant downregulation of the cytochrome C (p ≤ .0001), Bcl2 (p = .0002, p = .0007) and JNK3 (p = .042) genes. Rabies pathogenesis is multifactorial, involving both virus and host influences on the course of the infection.



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Effect of recombinant glutathione S-transferase as vaccine antigen against Rhipicephalus appendiculatus and Rhipicephalus sanguineus infestation

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Gabriela Alves Sabadin, Luís Fernando Parizi, Irene Kiio, Marina Amaral Xavier, Renata da Silva Matos, Maria Izabel Camargo-Mathias, Naftaly Wang'ombe Githaka, Vish Nene, Itabajara da Silva Vaz
The ticks Rhipicephalus appendiculatus and Rhipicephalus sanguineus are the main vectors of Theileria parva and Babesia spp. in cattle and dogs, respectively. Due to their impact in veterinary care and industry, improved methods against R. appendiculatus and R. sanguineus parasitism are under development, including vaccines. We have previously demonstrated the induction of a cross-protective humoral response against Rhipicephalus microplus following vaccination with recombinant glutathione S-transferase from Haemaphysalis longicornis tick (rGST-Hl), suggesting that this protein could control tick infestations. In the present work, we investigated the effect of rGST-Hl vaccine against R. appendiculatus and R. sanguineus infestation in rabbits. In silico analysis revealed that GST from H. longicornis, R. appendiculatus and R. sanguineus have >80% protein sequence similarity, and multiple conserved antigenic sites. After the second vaccine dose, rGST-Hl-immunized rabbits showed elevated antibody levels which persisted until the end of experiment (75 and 60 days for R. appendiculatus and R. sanguineus, respectively). Western blot assays demonstrated cross-reactivity between anti-rGST-Hl antibodies and native R. appendiculatus and R. sanguineus GST extracts from ticks at different life stages. Vaccination with rGST-Hl decreased the number, weight, and fertility of engorged R. appendiculatus adults, leading to an overall vaccine efficacy of 67%. Interestingly, histological analysis of organ morphology showed damage to salivary glands and ovaries of R. appendiculatus adult females fed on vaccinated animals. In contrast, rGST-Hl vaccination did not affect R. appendiculatus nymphs, and it was ineffective against R. sanguineus across the stages of nymph and adult. Taken together, our results show the potential application of rGST-Hl as an antigen in anti-tick vaccine development, however indicating a broad difference in efficacy among tick species.

Graphical abstract

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Induction of a balanced IgG1/IgG2 immune response to an experimental challenge with Mycoplasma bovis antigens following a vaccine composed of Emulsigen™, IDR peptide1002, and poly I:C

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Tracy Prysliak, Teresia Maina, Lu Yu, Muhammad Suleman, Steve Jimbo, Jose Perez-Casal
Prevention and or control of Mycoplasma bovis infections in cattle have relied on the treatment of animals with antibiotics; herd management including separation and or culling infected animals; and the use of vaccines with limited protection. Due to the negative reactions and incomplete protection observed after vaccination with some bacterin-based vaccines, there is a need to put more efforts in the development of recombinant-based vaccines. However, the arsenal of antigens that may be suitable for a fully protective vaccine is rather limited at this point. We have tested a vaccine formulation containing M. bovis proteins formulated with adjuvants that have been shown to aid in the protection against other pathogens. After vaccinations, the animals were challenged using a BHV-1/M. bovis co-infection model. While the PBMC proliferation and cytokine responses to the antigens in the vaccine were negligible, humoral responses reveal that eight antigens elicit a balanced IgG1/IgG2 response although this was not enough to confer protection against M. bovis.



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Reactogenicity and safety assessment of an attenuated nanovaccine against scorpion envenomation: Preclinical study

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Faez Amokrane Nait Mohamed, Abdelmounaim Nouri, Fatima Laraba-Djebari
An attenuated nanovaccine (Nps – V^∗) has been developed to protect humans from fatal scorpion envenomation in at-risk regions. This study was conducted to evaluate the toxicity and the local reactogenicity of the Nps – V^∗ nanovaccine developed against Androctonus australis hector (Aah) venom. Assessment of the systemic inflammatory response and serum cytokine levels were evaluated in vaccinated mice with 100μg of irradiated Aah venom (V^∗) encapsulated or not into polymeric calcium-alginate nanoparticles (Nps) and injected by subcutaneous (s.c) route. The local reactogenicity was evaluated by dermal Draize observations and skin tissue analysis at the injection site of vaccinated rabbits with 250 or 500μg of V^∗-loaded into Nps. All animals gained weight and had normal food consumption during the study. Additionally, results showed that the nanoformulation Nps – V^∗ did not cause clinical evidence of systemic toxicity in mice or rabbits, a transient edema/erythema at the injection site was only recorded as treatment-related reactogenicity. These results indicated a favorable safety profile for Nps – V^∗ and supported its use in superior animal tests, then in a Phase 1 clinical trial.



http://ift.tt/2j3OLGb

An imputation method for calculating and comparing autoimmune disease incidence using partial case review

Publication date: 4 December 2017
Source:Vaccine, Volume 35, Issue 48, Part B
Author(s): Jeff Slezak, Kristin Meyer, Lina S. Sy, Chun Chao, Harpreet Takhar, Brad Ackerson, T. Craig Cheetham, Steven Jacobsen
PurposeEstimate incidence of autoimmune conditions in a population who received HPV4 vaccine and a comparison unvaccinated population. Electronic health record (EHR) data may contain inaccurate or incomplete coding, while manual chart review of all cases may not be feasible. We propose a method to estimate incidence using EHR data and case review for a sample.MethodsSuspected incident cases were identified using ICD-9 codes, laboratory results and medications related to the condition. A random sample of charts was reviewed to confirm the diagnosis and determine disease onset date. Multiple imputation, using a Monte Carlo model including age and disease indicators was used to impute case status of non-reviewed cases. Incidence rate was calculated in each imputed dataset, with median and percentiles giving a distribution for the estimated incidence rate. Sensitivity analyses compared modeled results to results without imputation and results where imputation was applied to the subset of cases identified using specific ICD-9 codes.ResultsThe model accounted for differential case confirmation rates by age and method of case identification, identifying a potential safety signal that was missed relying on EHR data alone.ConclusionsThis method may be useful for computing incidence when full case review is not feasible.



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Organic synthesis in flow for medicinal chemistry

Publication date: 1 December 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 23
Author(s): Thomas Wirth




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The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

Publication date: 1 December 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 23
Author(s): Péter Bana, Róbert Örkényi, Klára Lövei, Ágnes Lakó, György István Túrós, János Éles, Ferenc Faigl, István Greiner
Recent advances in the field of continuous flow chemistry allow the multistep preparation of complex molecules such as APIs (Active Pharmaceutical Ingredients) in a telescoped manner. Numerous examples of laboratory-scale applications are described, which are pointing towards novel manufacturing processes of pharmaceutical compounds, in accordance with recent regulatory, economical and quality guidances. The chemical and technical knowledge gained during these studies is considerable; nevertheless, connecting several individual chemical transformations and the attached analytics and purification holds hidden traps. In this review, we summarize innovative solutions for these challenges, in order to benefit chemists aiming to exploit flow chemistry systems for the synthesis of biologically active molecules.

Graphical abstract

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Improving the throughput of batch photochemical reactions using flow: Dual photoredox and nickel catalysis in flow for C(sp2)C(sp3) cross-coupling

Publication date: 1 December 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 23
Author(s): Irini Abdiaj, Jesús Alcázar
We report herein the transfer of dual photoredox and nickel catalysis for C(sp²)C(sp³) cross coupling form batch to flow. This new procedure clearly improves the scalability of the previous batch reaction by the reactor's size and operating time reduction, and allows the preparation of interesting compounds for drug discovery in multigram amounts.

Graphical abstract

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A photochemical flow reactor for large scale syntheses of aglain and rocaglate natural product analogues

Publication date: 1 December 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 23
Author(s): Han Yueh, Qiwen Gao, John A. Porco, Aaron B. Beeler
Herein, we report the development of continuous flow photoreactors for large scale ESIPT-mediated [3+2]-photocycloaddition of 2-(p-methoxyphenyl)-3-hydroxyflavone and cinnamate-derived dipolarophiles. These reactors can be efficiently numbered up to increase throughput two orders of magnitude greater than the corresponding batch reactions.

Graphical abstract

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High throughput photo-oxidations in a packed bed reactor system

Publication date: 1 December 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 23
Author(s): Caleb J. Kong, Daniel Fisher, Bimbisar K. Desai, Yuan Yang, Saeed Ahmad, Katherine Belecki, B. Frank Gupton
The efficiency gains produced by continuous-flow systems in conducting photochemical transformations have been extensively demonstrated. Recently, these systems have been used in developing safe and efficient methods for photo-oxidations using singlet oxygen generated by photosensitizers. Much of the previous work has focused on the use of homogeneous photocatalysts. The development of a unique, packed-bed photoreactor system using immobilized rose bengal expands these capabilities as this robust photocatalyst allows access to and elaboration from these highly useful building blocks without the need for further purification. With this platform we were able to demonstrate a wide scope of singlet oxygen ene, [4+2] cycloadditions and heteroatom oxidations. Furthermore, we applied this method as a strategic element in the synthesis of the high-volume antimalarial artemisinin.

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Editorial board

Publication date: 1 December 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 23





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Generation of hazardous methyl azide and its application to synthesis of a key-intermediate of picarbutrazox, a new potent pesticide in flow

Publication date: 1 December 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 23
Author(s): Daisuke Ichinari, Aiichiro Nagaki, Jun-ichi Yoshida
Generation and reactions of methyl azide (MeN3) were successfully performed by using a flow reactor system, demonstrating that the flow method serves as a safe method for handling hazardous explosive methyl azide. The reaction of NaN3 and Me2SO4 in a flow reactor gave a MeN3 solution, which was used for Huisgen reaction with benzoyl cyanide in a flow reactor after minimal washing. The resulting 1-methyl-5-benzoyltetrazole serves as a key intermediate of picarbutrazox (IX), a new potent pesticide.

Graphical abstract

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Continuous-flow synthesis using a column reactor packed with heterogeneous catalysts: A convenient production of nitroolefins by using amino-functionalized silicagel

Publication date: 1 December 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 23
Author(s): Haruro Ishitani, Yuichi Furiya, Shū Kobayashi
A continuous-flow synthesis of β-nitroolefins by using heterogeneous base catalysts has been developed. Although the use of an excess amount of nitro-donor such as nitromethane is required in conventional methods, nearly equimolar amounts of nitro-donors and carbonyl compounds are sufficient for high-yielding production of nitroolefins. Catalysts for this flow protocol are inexpensive and abundant, and high durability and high productivity were also realized by using an appropriate second support.

Graphical abstract

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Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy

Publication date: Available online 15 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Fabien Hammerer, Florent Poyer, Laura Fourmois, Su Chen, Guillaume Garcia, Marie-Paule Teulade-Fichou, Philippe Maillard, Florence Mahuteau-Betzer
The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency.

Graphical abstract

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Podophyllotoxin derivatives as an excellent anticancer aspirant for future chemotherapy: A key current imminent needs

Publication date: Available online 16 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Xu Zhang, K.P. Rakesh, C.S. Shantharam, H.M. Manukumar, A.M. Asiri, H.M. Marwani, Hua-Li Qin
Cancer is one of the leading groups of threatened caused by abnormal state cell growth and second leading diseases involved in the major global death. To treat this, research looking for promising anticancer drugs from natural resource, or synthesized novel molecules by diverse group of scientists worldwide. Currently, drugs get into clinical practices and showing side effects with target actions which in turn leading to multidrug resistance unknowingly. Podophyllotoxin, a naturally occurring lignan and its hybrids have become one of the most attractive subjects due to their broad spectrum of pharmacological activities. Podophyllotoxin derivatives have been the centre of attention of extensive chemical amendment and pharmacological investigation in modern decades. Mainly, the innovation of the semi-synthetic anticancer drugs etoposide and teniposide has stimulated prolonged research interest in this structural phenotype. The present review focuses mainly onnew anticancer drugs from podophyllotoxin analogs, mechanism of action and their structure-activity relationships (SAR) as potential anticancer candidates for future discovery of suitable drug candidates.

Graphical abstract

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Status and interrelationship of toenail elements in Pacific children

Publication date: March 2018
Source:Journal of Trace Elements in Medicine and Biology, Volume 46
Author(s): Shamshad Karatela, Neil I. Ward, Irene Suilan Zeng, Janis Paterson
ObjectiveElemental deficiencies or in excess effects growth and development. Pacific population are at a disadvantage due to food insecurity as compared to New Zealand European households. This study aims to evaluate the status and interrelationship of elements (essential, non-essential and toxic) in nine-year-old Pacific children who were part of the Pacific Island Families Study living in New Zealand.Materials andMethodsThis observational study included 278 eligible nine-year-old children. Essential elements (including calcium, chromium, cobalt, copper, iodine, iron, magnesium, manganese, selenium, zinc, molybdenum), non-essential and toxic elements (arsenic, aluminum, antimony, boron, cadmium, lead, mercury, nickel,) were determined in toenails and after acid digestion, analysed using inductively coupled plasma mass spectrometry. Principal component analysis and multivariate analysis of covariance was used to identify differences in the groups of elements and the inter-correlations between elements.ResultsThe mean calcium (868μg/g Ca), selenium (0.35μg/g Se) and zinc (129μg/g Zn) concentrations were lower while the mean cadmium (0.21μg/g Cd) lead (0.86μg/g Pb) and mercury (0.72μg/g Hg) concentrations were higher than the optimal health requirements. Ethnic differences in relation to toenail elemental concentrations were observed for aluminium and iron. Gender differences were observed for aluminium, antimony, arsenic and lead. Selenium and molybdenum were inversely associated with mercury. Manganese, zinc and calcium were positively associated.ConclusionsThis research contributes to the understanding of the elemental concentrations for Pacific children by using tissue samples from toenails, which improves the completeness of sampling than other tissues and provides a longer exposure time frame. The study also reports several inter-correlations between essential, non-essential and toxic elements in Pacific Island population.



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Optical and structural analysis of ZnS core-shell type nanowires

Publication date: 5 March 2018
Source:Journal of Alloys and Compounds, Volume 736
Author(s): J.R. Ramos, C. Morales, G. García, T. Díaz, E. Rosendo, J. Santoyo, A.I. Oliva, R. Galeazzi
ZnS core-shell type nanowires were grown by the hot filament chemical vapor deposition technique using ZnS powders as solid source and molecular hydrogen as reactant gas. The growth temperature was varied ranging from 200 to 400 °C. X-ray diffraction patterns and micro-Raman spectra show that the grown material is formed by hexagonal and cubic crystalline ZnS combined phases. Micrographs revealed the formation of nanostructures with a pyramidal morphology ending with long tips. The tip endings measurement gives 600 nm-length and 20 nm-diameter. High resolution images indicate the formation of the core-shell type nanostructures with metallic zinc core and polycrystalline ZnS shell. The photoluminescence spectra of the nanowires are caused by native defects, elemental sulfur species on the surface and structural defects in the nanostructures.



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Hierarchically porous Zn-Co-O NCs-in-carbon hollow microspheres with high rate-capacity and cycle stability as anode materials for lithium-ion batteries

Publication date: 5 March 2018
Source:Journal of Alloys and Compounds, Volume 736
Author(s): Chuan Ding, Xiaoshu Jiang, Xiaohong Huang, Hu Zhang, Wenqing Zhong, Yifei Xia, Chongjiang Dai
Zn-Co-O/C hollow microspheres composed of center hole with an average size of 400 nm and ∼30 nm thicked porous carbon walls inlaid homogenously with ∼5.2 nm Zn-Co-O nanocrystals are successfully prepared for the first time via a Na-citrate mediated solvothermal method and a subsequent annealing process of Zn-Co-ethylene glycolate (Zn-Co-EG) precursor. The obtained powders were systematically characterized by XRD, IR, FESEM, TEM, BET and Raman techniques. The data indicate that the polymerization reaction of Zn-Co-EG crystals confined by Na-citrate should be responsible for the formation of the hollow microspherical precursors, which are then converted into the hierarchically porous Zn-Co-O/C hollow microspheres with complex microstructures after annealing at 450 °C for 3 h. These porous Zn-Co-O/C hollow microspheres used as an anode material for lithium-ion batteries exhibit a high reversible capacity of 991.7 mAh g⁻¹, 81.6% of the second cycle discharge capacity after 200 cycles at 1 A g⁻¹, and a high-rate delivery of 823.4 mAh g⁻¹ after 1000 cycles at 4 A g⁻¹. The superior performance of Zn-Co-O/C hollow microspheres is mainly attributed to the local dynamic confinement of tiny Zn-Co-O nanoparticles in the ultrathin porous carbon matrix.

Graphical abstract

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Regorafenib -- Benefit Assessment According to §35a Social Code Book V [Internet].

Background In accordance with § 35a Social Code Book (SGB) V, the Federal Joint Committee (G-BA) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to assess the benefit of the drug regorafenib. The assessment was based on a dossier compiled by the pharmaceutical company (hereinafter referred to as "the company"). The dossier was sent to IQWiG on 1 October 2015.

http://ift.tt/2za9van

Systematic Guideline Search and Appraisal, as Well as Extraction of Relevant Recommendations, for a DMP "Osteoporosis" [Internet].

Key statement Research question The aim of the present investigation is to identify current, topic-relevant, evidence-based guidelines, extract their recommendations and designate those recommendations that are relevant for the care of patients in a disease management programme (DMP) "osteoporosis".

http://ift.tt/2mAx5at

Ibrutinib -- Benefit Assessment According to §35a Social Code Book V [Internet].

Background In accordance with §35a Social Code Book (SGB) V, the Federal Joint Committee (G-BA) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to assess the benefit of the drug ibrutinib. The assessment was based on a dossier compiled by the pharmaceutical company (hereinafter referred to as "the company"). The dossier was sent to IQWiG on 1 February 2016.

http://ift.tt/2zb657e

Newborn Screening for Critical Congenital Heart Disease Using Pulse Oximetry [Internet].

Executive summary With its letter of 26 June 2013, the Federal Joint Committee (G-BA) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to assess newborn screening for critical congenital heart defects (CCHD) using pulse oximetry.

http://ift.tt/2mypr0d

A randomised placebo-controlled Phase III multicentre trial: low-dose intravenous immunoglobulin treatment for long-standing complex regional pain syndrome (LIPS trial).

Low-dose intravenous immunoglobulin was not effective in relieving pain in longstanding complex regional pain syndrome.

http://ift.tt/2zb5SAY

Insulin Degludec / Liraglutide (Addendum to Commission A15-15) [Internet].

Background On 8 September 2015, the Federal Joint Committee (G-BA) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to conduct a supplementary assessment for Commission A15-15 (Insulin degludec/liraglutide – Benefit assessment according to §35a SGB V).

http://ift.tt/2mAwSUJ

Netupitant / Palonosetron -- Benefit Assessment According to §35a Social Code Book V [Internet].

Background In accordance with §35a Social Code Book (SGB) V, the Federal Joint Committee (G-BA) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to assess the benefit of the drug netupitant / palonosetron. The assessment was based on a dossier compiled by the pharmaceutical company (hereinafter referred to as "the company"). The dossier was sent to IQWiG on 16 July 2015.

http://ift.tt/2zb8cIp

Méthodes d’identification et de quantification des moisissures de l’habitat : méthodes classiques, méthodes moléculaires

Publication date: Available online 15 November 2017
Source:Revue des Maladies Respiratoires
Author(s): E. Fréalle, V. Bex, G. Reboux, S. Roussel, S. Bretagne
IntroductionPour appréhender les répercussions de l'inhalation constante et inévitable de spores de moisissures il est nécessaire de les prélever, les identifier et les quantifier.État des lieuxLes prélèvements sont de trois types : (i) surfaces, de réalisation facile mais non quantifiables, (ii) air, faciles à calibrer mais limités dans le temps, et (iii) poussières, plus représentatifs dans le temps d'une exposition aux moisissures. La stratégie d'échantillonnage dépend des objectifs (exposition des personnes, objectiver la contamination, efficacité de la remédiation). L'identification des colonies obtenues en culture est réalisée par microscopie, Maldi-TOF, et/ou par séquençage ADN.PerspectivesLes capteurs à poussières, faciles à mettre en œuvre et peu coûteux, représentent une alternative pour la caractérisation qualitative et quantitative de la flore fongique lors des enquêtes à domicile. Le comptage des colonies devrait être progressivement associé aux méthodes de PCR quantitative en temps réel dans l'attente de standardisation des méthodes de séquençage à haut débit.ConclusionLa diversité des moisissures, du nombre de spores inhalées, et l'association à d'autres allergènes rendent l'évaluation des liens entre moisissures et impact sur la santé difficile, d'où l'importance du développement d'outils quantitatifs faciles à mettre en œuvre.IntroductionTo study the impact of the constant and inevitable inhalation of moulds, it is necessary to sample, identify and count the spores.BackgroundEnvironmental sampling methods can be separated into three categories: surface sampling is easy to perform but non quantitative, air sampling is easy to calibrate but provides time limited information, and dust sampling which is more representative of long term exposure to moulds. The sampling strategy depends on the objectives (evaluation of the risk of exposure for individuals; quantification of the household contamination; evaluation of the efficacy of remediation). The mould colonies obtained in culture are identified using microscopy, Maldi-TOF, and/or DNA sequencing.ViewpointsElectrostatic dust collectors are an alternative to older methods for identifying and quantifying household mould spores. They are easy to use and relatively cheap. Colony counting should be progressively replaced by quantitative real-time PCR, which is already validated, while waiting for more standardised high throughput sequencing methods for assessment of mould contamination without technical bias.ConclusionDespite some technical recommendations for obtaining reliable and comparable results, the huge diversity of environmental moulds, the variable quantity of spores inhaled and the association with other allergens (mites, plants) make the evaluation of their impact on human health difficult. Hence there is a need for reliable and generally applicable quantitative methods.



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Stratégies thérapeutiques chez les patients opérés pour un carcinome bronchique non à petites cellules. Résultats de l’étude ESCAP-2011-CPHG réalisée par le Collège des pneumologues des hôpitaux généraux (CPHG)

Publication date: Available online 15 November 2017
Source:Revue des Maladies Respiratoires
Author(s): F. Pinquié, F. Goupil, J.-P. Oster, A. Dixmier, P.-A. Renault, A. Lévy, J.-P. Mathieu, N. Paillot, F.C. Goutorbe, P. Masson, O. Molinier, D. Debieuvre, M. Grivaux
IntroductionESCAP-2011-CPHG a pour objectif de décrire le traitement du cancer bronchique primitif en pratique quotidienne. Cet article concerne les patients opérés d'un CBNPC.MéthodesDans cette étude de cohorte prospective menée dans 53 hôpitaux généraux, un formulaire standardisé était rempli à chaque changement de stratégie thérapeutique pendant les 2 ans suivant le diagnostic posé en 2010.RésultatsParmi les patients, 3943 étaient inclus, 3418 avaient un CBNPC, 741 (27,1 % ; stade 0-II, IIIA, IIIB, IV : 65 %, 27 %, 3 %, 5 %, respectivement) étaient opérés (chirurgie curative). Les opérés changeaient moins souvent de stratégie thérapeutique et étaient suivis plus longtemps que les non-opérés (suivi moyen : 23,3±9,3 mois vs 10,4±9,5 mois). Parmi les opérés en première stratégie (92,6 % des opérés), 56,9 % n'avaient pas reçu d'autre traitement, 34,7 % avaient une chimiothérapie, 5,9 % une radiochimiothérapie, 2,6 % une radiothérapie. À la fin du suivi, 55,8 % étaient vivants sans autre stratégie, 13,1 % étaient décédés, et 31,1 % avaient reçu au moins un deuxième traitement. Les patients opérés en seconde stratégie avaient bénéficié pour 63 % d'une chimiothérapie seule en première stratégie.ConclusionsESCAP-2011-CPHG permet l'évaluation des pratiques professionnelles dans la prise en charge chirurgicale du CBNPC en hôpital général. Elle met en évidence certaines divergences entre les référentiels nationaux et les stratégies thérapeutiques mises en œuvre dans la « vraie vie ».BackgroundThe aim of ESCAP-2011-CPHG, promoted by the French College of General Hospital Respiratory Physicians, was to describe therapeutic strategies in lung cancer in the first 2 years after diagnosis, in a real-life setting. This article focuses on patients undergoing surgical management of a non-small cell lung cancer (NSCLC).MethodsA prospective multicentre study was conducted in 53 French general hospitals. For each patient with lung cancer diagnosed in 2010, a standardised form was completed following each change in treatment strategy up to 2 years after diagnosis.ResultsOverall, 3418 of the 3943 included patients had NSCLC. 741 patients (21.7%) underwent curative surgery (stage 0-II, IIIA, IIIB, and IV: 65%, 27%, 3% and 5%, respectively). The therapeutic strategy changed less often in surgical than non-surgical patients and average follow-up time was longer: 23.3 months (SD: 9.3) versus 10.4 months (SD: 9.5) for non-surgical patients. Among patients with a surgical first strategy (92.6% of surgical patients as a whole), 56.9% did not receive any other treatment, 34.7% received chemotherapy, 5.9% radio-chemotherapy, 2.6% radiotherapy. At the end of follow-up, 55.8% were still alive without any other strategy, 13.1% had died, and 31.1% had received at least one more strategy. Among patients with a surgical second strategy, 63% had received chemotherapy alone during the first strategy.ConclusionsESCAP -2011- CPHG assessed everyday professional practice in the surgical management of NSCLC in general hospitals. It pointed out the discrepancies between current guidelines and the therapeutic strategies applied in real life conditions.



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Hormone therapy and patients satisfaction with treatment, in a large cohort of diverse disorders of sex development (DSD)

Abstract

Objectives

To describe and investigate the hormone treatments in individuals with different forms of disorders of sex development (DSD), and the patients own views on their treatment.

Design: Multicentre cross-sectional clinical evaluation, dsd-LIFE in six European countries from 02/2014 to 09/2015.

Participants

1040 adolescents and adults (≥16 years) with different DSD conditions.

Main outcomes measures: Hormone replacement, information received and patient satisfaction.

Results

Included were women with Turner syndrome (301), 46,XX GD (n=20), and women with 45,X/46XY (n=24). Individuals with Klinefelter syndrome (n=218), 46,XX males (n=6), Individuals with different forms of 46,XY DSD, (n=243): 46,XY DSD conditions (n=222), men with 45,X/46XY (n=21) 46,XX CAH, (n=226).

Oestrogens +/- progestins was used by 306 (81%) individuals, 72 (19%) received ethinylestradiol and 198 had testosterone treatment.

The overall adherence was good, with 10% of women with oestrogen and 5% of those on testosterone had stopped the medication despite 20% reporting dissatisfaction with the treatment, mostly because of psychological side effects. Glucocorticoid replacement was in patients with CAH was very seldom stopped.

More than 75% were satisfied with the information about the treatment but the satisfaction with information about treatment options and side effects was lower.

Conclusions

More than 50% in the total cohort had hormone replacement. Although adherence was generally good, this study shows that hormone replacement therapy may be improved. This may be achieved by better individualization of the treatment and by providing specific information to patients regarding both long term and short-term hormonal effects and side effects.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jxAqpr

The influences of separators on capacitive deionization systems in the cycle of adsorption and desorption

Abstract

This research focused on the influence of different separator compartments on the performance of capacitive deionization (CDI) cells in terms of brackish water treatment. For comparison, different separators including filter paper(FP), carbon nanotube (CNT), and stainless steel fiber (SSF) on deionization and desorption rate of salt were examined. The best performance was obtained when the CNT separator was packed, followed by SSF and FP. Reducing the cell voltage from 1.2 to 0.4 V decreased the salt removal and electrode regeneration rate of SSF-CDI. Electrochemical impedance spectrometry (EIS) analysis revealed that the resistance and specific capacitance of separator materials are essential to the desalination and desorption performance of CDI. The electric double layers (EDLs) accelerated the ion transfer in the flow chamber due to storing excess ions, therefore increasing the desalination and electrode regeneration rate.

http://ift.tt/2jAy5dr

A 10-year follow-up study of completers versus dropouts following treatment with an integrated cognitive-behavioral group therapy for eating disorders

Abstract

Background

Cognitive-behavioral therapy (CBT) has been recommended for the treatment of eating disorders, and group therapy is known to have certain advantages over individual therapy. The aim of the current study was to compare the 10-year prognosis of patients who completed integrated group CBT with those who dropped out and to examine the effect of completion of group CBT on the prognosis.

Methods

The participants were 65 adult patients with eating disorders. All patients were women and Japanese. The average age (19–37) of the patients was 25.1 ± 3.8 years, and the average body mass index (BMI) was 17.7 ± 2.0. We conducted integrated group CBT with the patients and compared eating disorder symptoms, mood states, coping styles, and self-esteem before and after therapy. Furthermore, we compared clinical features and the 10-year prognosis of patients who completed the treatment and those who dropped out.

Results

After 10 sessions of group therapy, Eating Attitudes Test scores, Profile of Mood States depression scores, and Coping Inventory for Stressful Situations emotion-oriented scores decreased, while Rosenberg's Self-Esteem Scale scores increased. Regarding the results of the 10-year follow up, the completer group had more patients with a good prognosis. In contrast, the dropout group had more patients with a poor prognosis.

Conclusions

Those who completed the integrated group CBT had a good prognosis. Group therapy gives the patients an opportunity to form peer relationships, and helps them to develop communication and socialization skills. Furthermore, in the group therapy sessions, the patients develop self-awareness by listening to other members of the group and they also develop interpersonal relationships. This effect may be temporary, but experience of group therapy may provide hope for the patient and increase the chance of the patient continuing treatment.

Trial registration

Retrospectively registered in University Hospital Medical Information Network in Japan: No. 000028868 (May 19th, 2017).

http://ift.tt/2A77Jae

Morphology, molecular structure, and stable carbon isotopic composition of black carbon (BC) in urban topsoils

Abstract

Urban soils contain significant amounts of black carbon (BC) from biomass and fossil fuel combustion and regard to be a pool of BC. BC in urban soils has multiple effects on environmental processes in urban system, such as global climate change, air quality, and public health. Urban topsoil samples (0–10 cm) were collected from Anshan, Liaoning Province, northeast China, which is one of the most important old steel industrial bases in China. The BC in urban topsoils was extracted using the density method. Their chemical composition, morphology, molecular structure, and stable carbon isotopic composition were examined using elemental analysis, scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and stable carbon isotope (δ¹³C). Elemental analysis shows that carbon content in the BC of studied soils ranged from 64.5 to 78.4%, with the average more than 70%. The O/C atomic ratio of BC is on average 0.18. The BC particle displays different morphology, including porous spherical, irregular porous fragmentary, and blocky shapes. The porous spherical BC particles has atomic molar O/C ratio determined by SEM-EDS ranging from 0.04 to 0.37. XRD indicates that BC exists in mainly combining with mineral phases hematite (Fe₂O₃), kaolinite (Al₂Si₂O₅(OH)₄), quartz (SiO₂), and calcite (CaCO₃). The FTIR spectra of BC particles show major bands at approximately 3400 cm⁻¹ (O–H), 2920 cm⁻¹ (C = H), 1600 cm⁻¹ (C = C), 1230 cm⁻¹ (C = O), and 1070 cm⁻¹ (C = O). The stable carbon isotope (δ¹³C) of BC ranges from −24.48 to −23.18‰ with the average of −23.79 ± 0.39‰. The concentration of BC in the industrial area is significantly (p < 0.05) higher than that in the roadside area. The BC of industrial area is characterized by porous spherical structure, suggesting that they are mainly derived from fossil fuel combustion. Results indicated that a combination of atomic O/C ratio, porous structure, and stable carbon isotopic (δ¹³C) of BC could reflect effectively the origin of BC in urban topsoils. It could conclude that BC in Anshan urban topsoil was mainly from fossil fuel combustion.

http://ift.tt/2ySo26v

Editorial Board and Contents

Publication date: December 2017
Source:Trends in Cell Biology, Volume 27, Issue 12





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Endothelial Cell Metabolism in Health and Disease

Publication date: Available online 16 November 2017
Source:Trends in Cell Biology
Author(s): Katerina Rohlenova, Koen Veys, Ines Miranda-Santos, Katrien De Bock, Peter Carmeliet
The metabolism of endothelial cells (ECs) has only recently been recognized as a driving force of angiogenesis. Metabolic pathways, such as glycolysis, fatty acid oxidation, and glutamine metabolism, have distinct, essential roles during vessel formation. Moreover, EC metabolism is markedly perturbed in pathologies such as cancer and diabetes. For instance, because tumor ECs increase glycolysis, lowering hyperglycolysis in tumor ECs induces therapeutic benefits in preclinical tumor models. Expanding our knowledge of how ECs alter their metabolism in disease could pave the way for novel therapeutic opportunities. In this review, we discuss the most recent insights into EC metabolism in health and disease, with emphasis on the changes in metabolism in the tumor endothelium.



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Impact of hybrid PET/MR technology on multiparametric imaging and treatment response assessment of cervix cancer

Publication date: Available online 15 November 2017
Source:Radiotherapy and Oncology
Author(s): Michaela Daniel, Piotr Andrzejewski, Alina Sturdza, Katarina Majercakova, Pascal Baltzer, Katja Pinker, Wolfgang Wadsak, Markus Mitterhauser, Richard Pötter, Petra Georg, Thomas Helbich, Dietmar Georg
Background and purposeMultimodal tissue characterization by combined MRI and PET has high clinical potential in the context of sub-target definition for dose painting and response assessment but its clinical exploration is yet limited. The aim of this study was to prove the potential and feasibility of hybrid PET/MRI to non-invasively measure tumor hypoxia, perfusion and microstructure at one stop in tumors of the uterine cervix during chemoradiotherapy.Material and methodsTen cervix cancer patients were subjected to simultaneous multiparametric PET/MRI with [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO). Imaging was scheduled before, twice during and after chemoradiotherapy. Intra- and inter-time point analyses of the extracted parameters (i.e. ADC, K^trans, ABrix, [¹⁸F]FMISO-tumor to background ratio (TBR)) were performed. The [¹⁸F]FMISO uptake- and ADC-spatio-temporal changes were assessed.ResultsPatient averaged ADC values increased from baseline to follow up (1.03 ± 0.11/1.30 ± 0.13 × 10⁻³ mm²/s), while the TBR decreased (1.73 ± 0.24/1.36 ± 0.19), K^trans dropped over time (0.17 ± 0.05/0.05 ± 0.05 min⁻¹); for all above p < 0.05. None of these parameters correlated significantly on a voxel-by-voxel basis. Low-ADC regions spatially varied over time. There was pronounced reduction of the [¹⁸F]FMISO-avid volumes during treatment.ConclusionsThe suggested hybrid PET/MRI protocol to non-invasively investigate tumor hypoxia, perfusion and microstructure at one stop was feasible, revealing spatio-temporal response patterns that could be utilized for comprehensive sub-target definition for dose painting and response assessment.



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Late normal tissue effects in the arm and shoulder following lymphatic radiotherapy: Results from the UK START (Standardisation of Breast Radiotherapy) trials

Publication date: Available online 15 November 2017
Source:Radiotherapy and Oncology
Author(s): Joanne S Haviland, Mariella Mannino, Clare Griffin, Nuria Porta, Mark Sydenham, Judith M. Bliss, John R. Yarnold
Background and purposeAdjuvant lymphatic radiotherapy (LNRT) is recommended for selected axillary node positive women with early breast cancer. We investigated whether hypofractionated LNRT is safe combined with similarly-hypofractionated breast/chest wall radiotherapy (RT).Material and methodsThe Standardisation of Breast Radiotherapy (START) pilot, A and B trials randomised women with early breast cancer to schedules of 2.67–3.3 Gy versus 2.0 Gy fractions (control). RT adverse effects were assessed by patients using the EORTC QLQ-BR23 and protocol-specific questions, and by physicians. Rates of arm/shoulder effects were compared between schedules for patients given LNRT.Results864/5861 (14.7%) patients received LNRT (385 START-pilot, 318 START-A, 161 START-B). Prevalences of moderate/marked arm/shoulder effects were low up to 10 years. There were no significant differences between the hypofractionated and control groups for patient- and physician-assessed symptoms in START-A or START-B. In START-pilot, adverse effect rates were higher after 13 fractions of 3.3 Gy, consistent with effects reported in the breast/chest wall (significant for shoulder stiffness, HR 3.07, 95%CI 1.62–5.83, p = 0.001).ConclusionsThe START trial results suggest that appropriately-dosed hypofractionated LNRT is safe in the long-term, according to patient and physician-assessed arm and shoulder symptoms. These findings are consistent with those reported after the same schedules delivered to the breast/chest wall.



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International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma

Publication date: Available online 15 November 2017
Source:Radiotherapy and Oncology
Author(s): Anne W. Lee, Wai Tong Ng, Jian Ji Pan, Sharon S. Poh, Yong Chan Ahn, Hussain AlHussain, June Corry, Cai Grau, Vincent Grégoire, Kevin J. Harrington, Chao Su Hu, Dora L. Kwong, Johannes A. Langendijk, Quynh Thu Le, Nancy Y. Lee, Jin Ching Lin, Tai Xiang Lu, William M. Mendenhall, Brian O'Sullivan, Enis Ozyar, Lester J. Peters, David I. Rosenthal, Yoke Lim Soong, Yungan Tao, Sue S. Yom, Joseph T. Wee
PurposeTarget delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome.MethodA review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies.ResultsCommon areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisions were made based on extensive discussion and final voting on controversial areas by the expert panel, to formulate the recommendations on contouring of CTV based on optimal geometric expansion and anatomical editing for those structures with substantial risk of microscopic infiltration.ConclusionThrough this comprehensive review of available evidence and best practices at major institutions, as well as interactive exchange of vast experience by international experts, this set of consensus guidelines has been developed to provide a practical reference for appropriate contouring to ensure optimal target coverage. However, the final decision on the treatment volumes should be based on full consideration of individual patients' factors and facilities of an individual centre (including the quality of imaging methods and the precision of treatment delivery).



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Scholar : These new articles for Pediatric Hematology and Oncology are available online

The online platform for Taylor & Francis Online content New for Pediatric Hematology and Oncology and online now on Taylor & Francis Online: Original Articles Prognostic impact of CD200 and CD56 expression in pediatric B-cell acute lymphoblastic leukemia patients Salah Aref, Emad Azmy, Kadry El-bakry, Lobna Ibrahim & Sherin Abdel Aziz Pages: 1-11 | DOI: 10.1080/08880018.2017.1363836 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Advances in Mental Health are available online

The online platform for Taylor & Francis Online content New for Advances in Mental Health and online now on Taylor & Francis Online: Original Articles Experiences of a day treatment service using phenomenological analysis: 'Six weeks of little steps in the right direction' Rachel H. Tribe, Malgorzata Bielawska & Derek K. Tracy Pages: 1-17 | DOI: 10.1080/18387357.2017.1404432 Who do they think we are? Public perceptions of psychiatrists and psychologists Krisna Patel , Caroline Caddy & Derek K Tracy Pages: 1-12 | DOI: 10.1080/18387357.2017.1404433 2018 Future Directions Forum JOIN US at the 2018 Future Directions Forum for Journal of Clinical Child & Adolescent Psychology - June 15-16, 2018 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Canadian Water Resources Journal / Revue canadienne des ressources hydriques are available online

The online platform for Taylor & Francis Online content New for Canadian Water Resources Journal / Revue canadienne des ressources hydriques and online now on Taylor & Francis Online: Original Articles Hydrogeochemical evolution and groundwater mineralization of shallow aquifers in the Bas-Saint-Laurent region, Québec, Canada Gwénaëlle Chaillou , Maud Touchette, Thomas Buffin-Bélanger, Claude-André Cloutier, Bernard Hétu & Marie-Andrée Roy Pages: 1-16 | DOI: 10.1080/07011784.2017.1387817 Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

White matter changes in corpus callosum in a patient with idiopathic normal pressure hydrocephalus

Naresh Mullaguri, Anusha Battineni, Christopher R Newey, Premkumar Nattanmai

Journal of Neurosciences in Rural Practice 2017 8(4):657-659

Idiopathic normal pressure hydrocephalus (INPH) is characterized by the clinical triad of gait and cognitive dysfunction and urinary incontinence. Ventriculoperitoneal (VP) shunting is often required for treatment. Review of literature shows few case reports discussing benign magnetic resonance imaging (MRI) T2 hyperintense changes in the corpus callosum of NPH patients after shunting due to mechanical compression of the middle and posterior regions of the body against falx cerebri leading to ischemic demyelination. These changes can be a delayed phenomenon and may interfere with clinical evaluation and may lead to unnecessary procedures and investigations. We present a patient with NPH who was admitted to the neurocritical care unit in coma with quetiapine and trazodone overdose. Diffuse changes in the body of the corpus callosum were seen on MRI suspicious for acute vasogenic edema due to drug overdose. However, it was later determined to be due to the VP shunting for the NPH. We report this case to raise the awareness of neuroimaging changes in patients with NPH who have VP shunting.

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Commentary

Amauri Dalla-Corte

Journal of Neurosciences in Rural Practice 2017 8(4):694-694



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Neurocardiology and atherosclerosis: The effect of ethnic differences on heart-brain interaction

George Markousis-Mavrogenis

Journal of Neurosciences in Rural Practice 2017 8(4):504-505



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Delayed visual loss following transcranial surgery for tuberculum sella meningioma

Sudha Menon, Girish Menon

Journal of Neurosciences in Rural Practice 2017 8(4):680-682

Postoperative visual loss is a dreaded complication following transcranial excision of tuberculum sella meningioma. Visual deterioration is commonly noticed immediately after surgery, and delayed deterioration after 72 h is uncommon. We report a case of delayed postoperative deterioration in a 48-year-old female and discuss the possible mechanisms.

http://ift.tt/2A7lrtr

Is indocyanine green videoangiography a good substitute for postoperative digital subtraction angiography

Girish Menon

Journal of Neurosciences in Rural Practice 2017 8(4):506-506



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Sir Hugh Cairns: The neurosurgeon who introduced crash helmets

Shahsivadhanan Sundaravadhanan

Journal of Neurosciences in Rural Practice 2017 8(4):647-648

Statistics prove that more Indians die in Road traffic related accidents than in wars. Prior to World War II, the death toll across the world used to be very high. It was at this juncture that a Military Neurosurgeon named Hugh Cairns introduced the compulsory wearing of crash helmets and brought about a reduction in mortality by more than 50%. Within a decade of introduction of crash helmets in Britain, the entire world followed suit. The results of his efforts are here for all of us to see. This innovative military neurosurgeon is credited as the one who introduced the concept of mobile neurosurgical units during world war and also the first proponent of usage of penicillin in war. His concepts in war surgery are still followed by militaries across the world. This article comes as a tribute to this great Neurosurgeon who helped in saving millions of lives.

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Knowledge, attitude, and practice among practitioners regarding epilepsy in Bhutan: A rural and a remote country

Devender Bhalla

Journal of Neurosciences in Rural Practice 2017 8(4):507-510

Purpose: Epilepsy is a major neurological disorder with many countries as scientifically silent and little-to-nothing known on various aspects of epilepsy. Methods: Taking background of a first multinational seminar on epilepsy in Bhutan and a short valid questionnaire pertaining to various aspects of epilepsy, before participation. Results: Large participation was achieved (76 out of 87 approached, 87.3%; 53.0% males). Based on the responses of 76.0% lecturers and clinician and medical administration, 21.0% nurses, and 3.0% traditional practitioners, important derivations were obtained: positively, (a) event provided at least an opportunity to bring service providers at a common platform toward initiating particular epilepsy goals, (b) none regarded epilepsy as contagious or due to past sins, (c) all responded favorably to that "they found this event useful' and 'this event added something meaningful to them personally or professionally," (d) large participation indicated acceptance, need, and common interest among a number of stakeholders. Negatively, significant knowledge-deficit was noted: for 38.4% electroencephalogram is essential for diagnosis, 48.0% responded with incorrect definition of epilepsy, etc. Conclusions: Events, such as this, provides, for scientifically silent countries, basis for not only bringing service providers to a common platform but also to discuss to initiate particular epilepsy goals, to provide additional professional knowledge for strengthening service development, and to determine need and social acceptance around epilepsy. Important knowledge deficit was identified which cannot be fully explained through lack of time or limited training. There might be a need to reappraise the approach to teaching medical professionals about epilepsy.

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Staged multimodality treatment of a large ruptured fusiform supraclinoid internal carotid artery aneurysm: Microsurgical clip-assisted endovascular coiling

Dale Ding, Thomas J Buell, Ching-Jen Chen, Daniel M Raper, Kenneth C Liu, Dennis G Vollmer

Journal of Neurosciences in Rural Practice 2017 8(4):668-671

In the contemporary era of aneurysm management, large fusiform aneurysms presenting with subarachnoid hemorrhage (SAH) remain particularly challenging lesions to successfully manage. We describe a staged, multimodal treatment strategy for a 71-year-old patient who presented with a large ruptured fusiform aneurysm of the supraclinoid internal carotid artery (ICA) and a fetal posterior communicating artery which originated from the inferomedial aspect of the aneurysm. In the first stage, we performed a partial microsurgical clip reconstruction of the fusiform aneurysm and secured its rupture site, which was identified intraoperatively. This left two residual saccular components of the aneurysm, which were targeted with endovascular coiling in the same hospitalization after the patient had convalesced from the SAH and was beyond the vasospasm window. We believe that this combined approach of clip-assisted coiling can be employed instead of endovascular flow diversion or microsurgical bypass for appropriately selected patients with ruptured fusiform ICA aneurysms.

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How long does denervation take in poliomyelitis? Or is it a lifetime?”

Mehmet Guney Senol, Cengiz Kaplan, Fatih Ozdağ, Mehmet Saraçoğlu

Journal of Neurosciences in Rural Practice 2017 8(4):511-515

Background and Objective: This study aims to determine the period of reinnervation in patients with poliomyelitis. This research was conducted to identify the appearance of denervation potentials in patients with poliomyelitis as indicators for reinnervation. Materials and Methods: A total of 246 male patients with poliomyelitis were assessed electrophysiologically between 1988 and 2007. The mean age was 22.8 (18–42). It has been an average of 19.9 ± 4.9 years since the beginning of complaints from the patients. Results: The patients had no complaints of newly developing muscle weakness, fatigue, muscle and joint pain, and difficulties in breathing and swallowing. Neurological examinations revealed the absence of myotomal pain and sensory loss. Upon assessment of the patients' limbs, the following findings were revealed: two patients had left upper and lower limb involvement, two patients had left upper and right lower limb involvement, 6 patients had left upper limb involvement, 12 patients had both lower limb involvement, 105 patients had left lower limb involvement, 1 patient had both upper limb involvement, 2 patients had right lower and upper limb involvement, 12 patients had right upper limb involvement, 6 patients had both lower limb involvement, 95 patients had right lower limb involvement, and 3 had all the three extremities affected. The needle electromyography revealed the presence of denervation potentials in 25.2% (62) of the patients. Conclusion: When poliovirus attacks the motor neuron, this neuron may be completely destroyed, damaged, or unaffected. Reinnervation occurs when nearby functioning motor units send out terminal axon sprouts to reinnervate the damaged muscle fibers. As a consequence of poliomyelitis, several muscle fibers become atrophic and fibrotic, but others continue to survive. This study showed that patients with a history of poliomyelitis experienced denervation with subsequent reinnervation for many years.

http://ift.tt/2zMCbps

Proprioceptive-induced reflex postinfarct seizures: A rare occurrence

Rohan Mahale, Anish Mehta, Rangasetty Srinivasa

Journal of Neurosciences in Rural Practice 2017 8(4):687-689



http://ift.tt/2A8HEHE

A clinical and electrophysiological study of peripheral neuropathies in predialysis chronic kidney disease patients and relation of severity of peripheral neuropathy with degree of renal failure

Dushyanth Babu Jasti, Sarat Mallipeddi, A Apparao, B Vengamma, V Sivakumar, Satyarao Kolli

Journal of Neurosciences in Rural Practice 2017 8(4):516-524

Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

http://ift.tt/2zLBQTI

A simplified overview of World Health Organization classification update of central nervous system tumors 2016

Anshu Gupta, Tanima Dwivedi

Journal of Neurosciences in Rural Practice 2017 8(4):629-641

After 8 years, an update of central nervous system (CNS) tumors was published in 2016 after 2007. First time ever, molecular markers along with histology have been used in classification of any tumor. Major changes are seen in glioma and medulloblastoma groups. Few entities have been added such as diffuse midline glioma, H3 K27M-mutant, RELA fusion-positive ependymoma, embryonal tumor with multilayered rosettes, C19MC-altered, and hybrid nerve sheath tumors. Few variants and patterns that no longer have diagnostic and/or biological relevance and have been deleted such as glioblastoma cerebri, protoplasmic and fibrillary astrocytoma, and cellular ependymoma. Other changes include deletion of term "primitive neuroectodermal tumor," addition of criterion of brain invasion in atypical meningioma, separation of melanotic schwannoma from other schwannoma, and combination of solitary fibrous tumors and hemangiopericytoma as one entity. There is also expansion of entities in nerve sheath tumors and hematopoietic/lymphoid tumors of the CNS. In this review article, we tried to review CNS tumors 2016 classification update in a simplified manner; comparing the differences between 2016 and 2007 CNS tumors classifications with brief description of important molecular markers and finally utility as well as challenges of this classification.

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Outcome of early versus delayed evacuation of spontaneous lobar hematomas in unconscious adults

Hazem M Alkosha, Wael K Zakaria

Journal of Neurosciences in Rural Practice 2017 8(4):525-534

Objective: To explore the difference in outcomes of medium-sized lobar hematomas evacuated in early versus delayed fashion among unconscious noncomatose individuals. Methods: A retrospective analysis of demographic, clinical, and radiological data of unconscious patients admitted with lobar hematomas during 18 years was performed. Time to surgery was compared in various patient variables and characteristics. Outcome groups (favorable and poor) were also compared to find out any association with surgery timing, as well as potential indicators of outcome and mortality. Results: The mean follow-up period in this study was 7.5 months after discharge. Two-thirds of the patients carried favorable prognosis at final follow-up with mortality (7.3%) included among poor cases. Time to surgery was not associated to any of the patient characteristics, except for international normalized ratio and associated chest problems which represented the main indicators of delayed surgery. Rebleeding after evacuation was associated with shorter time to surgery in clots ≤35 cc but not in the whole group. Poor outcome was significantly associated with higher basal glucose levels, bigger hematomas, rebleeding after surgery, and delayed evacuation of clots >35 cc. The presence of mild intraventricular hemorrhage (IVH) per se was not associated with increased mortality or poor outcome; however, its volume was. Conclusion: Smaller lobar hematomas (≤35 cc) in unconscious adults (Glasgow Coma Scale 8–13) may be managed with initial conservative treatment, while larger hematomas (>35 cc) are better evacuated as early as possible. Basal glucose levels and volume of mild IVH should be considered in the future management planes.

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Intracranial ossified metaplastic meningioma: Unusual cause of headache

Venkatraman Indiran

Journal of Neurosciences in Rural Practice 2017 8(4):653-653



http://ift.tt/2A6v37S

Predictors of dropout from outpatient mental health services; A study from Rohtak, India

Nikhil Jain, Sidharth Arya, Rajiv Gupta

Journal of Neurosciences in Rural Practice 2017 8(4):535-539

Context: Dropout from mental health services is problematic in both developed and developing nations and often leads to poor outcomes. There is a lack of hospital-based studies assessing the factors responsible for treatment dropout from mental health services in Indian settings. This study aims to contribute in that direction by presenting a study done in a tertiary care hospital in North India. Methodology: This was a hospital-based retrospective chart review carried out on randomly selected 139 patients at a tertiary hospital from January 1, 2014, to June 30, 2014. For this chart review, an abstraction form was designed that recorded six sociodemographic variables, nine clinical factors, and two outcome variables (more than one follow-up and active follow-up till 6 months). Results: Out of 139 patients, 53 patients dropped out after the first visit and 105 patients dropped out by the end of 6 months. Lower education status (odds ratio [OR] = 8.2, 95% confidence interval [CI]: 2.30–29.50), severe mental illness (OR = 2.6, 95% CI: 1.05–6.49), and early referral to clinical psychologist (CP) (OR = 7.8, 95% CI: 1.87–6.49) were predictors of better rates of follow-up after first visit. Lower education status (OR = 4.9, 95% CI: 1.45–17.08), early referral to CP (OR = 5.8, 95% CI: 2.09–38.35), and previous treatment history (OR = 8.9, 95% CI: 1.97–17.52) were predictors of better rates of follow-up at the end of 6 months. Conclusion: The findings that education status, diagnosis, utilizing services of CP, and psychiatric services in past are correlated with dropout rates may be helpful in targeting patients who are more vulnerable to dropping out of care in the given setting.

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Commentary

Pooja Patnaik Kuppili

Journal of Neurosciences in Rural Practice 2017 8(4):662-663



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Effect of scapular stabilization exercise during standing on upper limb function and gait ability of stroke patients

JO Kim, J Lee, BH Lee

Journal of Neurosciences in Rural Practice 2017 8(4):540-544

Background: The purpose of this study was to determine the effect of scapular stabilization exercise during standing on a paretic side on upper limb function and gait ability of stroke patients. Methods: This study was a hospital-based, randomized controlled trial with a blinded assessor. A total of 17 patients with hemiplegic diagnosis after stroke were divided into two groups (9 patients in a study group and 8 patients in a control group). The study group received physical therapy and scapular stabilization exercise on a paretic side. Participants were subjected to initial evaluation before the treatment. Subjects were subsequently re-evaluated 4 and 8 weeks later to compare the changes. Measurements of hand function and gait ability were performed. Results: Based on multivariate analysis of variance for repeated-measures, there was a significant time effect for Timed Up and Go test (TUG) (F = 13.816, P = 0.000), Functional Gait Assessment (FGA) (F = 18.613, P = 0.000), and manual function test (MFT) (F = 16.777, P = 0.000). The group × time interaction effect was also significant for FGA (F = 4.966, P = 0.024) and MFT (F = 6.946, P = 0.003), but not for TUG test (F = 3.343, P = 0.069). Conclusion: Results of the present study indicated that scapular stabilization exercise during standing on a paretic side for 8 weeks had an effect on hand function and gait ability of hemiplegic patients after stroke. Further studies are needed to find the most proper exercise for stroke patients who have gait disability and upper limb dysfunction.

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Commentary

Aaron Mohanty

Journal of Neurosciences in Rural Practice 2017 8(4):675-676



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Use of preoperative ependymal enhancement on magnetic resonance imaging brain as a marker of grade of glioma

Sumit Sharma, Shashi Kant Jain, Virendra Deo Sinha

Journal of Neurosciences in Rural Practice 2017 8(4):545-550

Objectives: Neural stem cells within the subventricular zone (SVZ) are thought to be responsible for the origin and the heterogeneous nature of the gliomas. The relationship of the gliomas to the SVZ can be appreciated as ependymal enhancement on contrast magnetic resonance imaging (MRI). This study evaluates the rate of ependymal enhancement and its association with the histopathological grade of gliomas. Patients and Methods: Seventy-five patients with radiological features of glioma were recruited. Preoperative MRI was evaluated for the presence of ependymal enhancement and fluid-attenuated inversion recovery (FLAIR) signal proximity of tumor to ependyma, and the association to grade was investigated. Results: Seventy-five patients studied showed a male predominance (62.66%) with a mean age of 44.91 ± 13.64 years. Evidence of ependymal enhancement was positive in 24% (n = 18), 46.67% (n = 35) showed no evidence, and in 29.33% (n = 22), assessment was inconclusive. According to WHO grading, 76% (n = 57) were high-grade gliomas (HGGs) including Grade III (n = 17) and Grade IV (n = 40) and 24% (n = 18) were low-grade gliomas (LGGs) Grade II. HGGs were significantly associated with ependymal enhancement (P < 0.01) and FLAIR signal proximity to the ependyma (P < 0.001). Among HGGs, rate of ependymal enhancement and FLAIR signal proximity was more in Grade IV than Grade III but was not statistically significant (P > 0.05). Conclusion: SVZ is associated with HGGs. These MRI features can be helpful in predicting the tumor grade preoperatively and by including LGGs, the role of SVZ in the heterogeneous disease process of glioma can be studied as a whole, not only in the glioblastoma (GBM).

http://ift.tt/2zKG6TK

Simultaneous convexity meningioma and prolactinoma

Vladimir Figueroa-Angel, Willem Guillermo Calderon-Miranda, Nidia Escobar-Hernandez, Andrei F Joaquim, Luis Rafael Moscote-Salazar, Emericella Renna Roldan-Medellin, Estefania Casasa Velez, Maria del Rocio Estrada-Hernandez

Journal of Neurosciences in Rural Practice 2017 8(4):684-685



http://ift.tt/2A7QjKA

Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)

Objective

Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation.

Design

Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals.

Methods

We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8).

Results

90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH.

Conclusions

Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

http://ift.tt/2APatFn

Time to parathyroid function recovery in patients with protracted hypoparathyroidism after total thyroidectomy

Objective

Hypocalcaemia is the most common adverse effect after total thyroidectomy. It recovers in about two-thirds of the patients within the first postoperative month. Little is known, however, about recovery of the parathyroid function (RPF) after this time period. The aim of the present study was to investigate the time to RPF in patients with protracted (>1 month) hypoparathyroidism after total thyroidectomy.

Design

Cohort prospective observational study.

Methods

Adult patients undergoing total thyroidectomy for goitre or thyroid cancer. Cases with protracted hypoparathyroidism were studied for RPF during the following months. Time to RPF and variables associated with RPF or permanent hypoparathyroidism were recorded.

Results

Out of 854 patients undergoing total thyroidectomy, 142 developed protracted hypoparathyroidism. Of these, 36 (4.2% of the entire cohort) developed permanent hypoparathyroidism and 106 recovered: 73 before 6 months, 21 within 6–12 months and 12 after 1 year follow-up. Variables significantly associated with RPF were the number of parathyroid glands remaining in situ (not autografted nor inadvertently resected) and a serum calcium concentration >2.25 mmol/L at one postoperative month. Late RPF (>6 months) was associated with surgery for thyroid cancer. RPF was still possible after one year in patients with four parathyroid glands preserved in situ and serum calcium concentration at one month >2.25 mmol/L.

Conclusions

Permanent hypoparathyroidism should not be diagnosed in patients requiring replacement therapy for more than six months, especially if the four parathyroid glands were preserved.

http://ift.tt/2ipMplK

Incidence, prevalence and seasonal onset variation of Addisons disease among persons with type 1 diabetes mellitus: nationwide, matched cohort studies

Objectives

We determined the incidence and prevalence of Addison's disease (AD) among persons with or without type 1 diabetes mellitus (T1DM) in nationwide, matched cohort studies.

Methods

Persons with T1DM were identified from the Swedish National Diabetes Register and each was matched for age, sex, year and county to five controls randomly selected from the general population. Persons with AD were identified from the Swedish National Inpatient Register. Baseline demographics and seasonal onset variation of AD were presented by descriptive statistics. Prevalence and incidence were estimated by proportions and incidence rates, respectively. Times to AD were analyzed using the Cox proportional hazard model.

Results

Between 1998 and 2013, 66 persons with T1DM were diagnosed with AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM, while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570 controls. The difference in mean age at diagnosis of AD between the groups was 6.3 years (P value = 0.036). The incidence of AD for a person with or without T1DM was therefore 193 and 18 per million person-years, respectively. The adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1–16.5). The highest incidence of AD was observed during February–March and September–October. The prevalence of AD in persons with or without T1DM in December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD in persons with T1DM vs controls was 16.5 (95% CI: 11.1–24.5).

Conclusion

The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern.

http://ift.tt/2AQdwNo

Excess morbidity and mortality in patients with craniopharyngioma: a hospital-based retrospective cohort study

Objective

Most studies in patients with craniopharyngioma did not investigate morbidity and mortality relative to the general population nor evaluated risk factors for excess morbidity and mortality. Therefore, the objective of this study was to examine excess morbidity and mortality, as well as their determinants in patients with craniopharyngioma.

Design

Hospital-based retrospective cohort study conducted between 1987 and 2014.

Methods

We included 144 Dutch and 80 Swedish patients with craniopharyngioma identified by a computer-based search in the medical records (105 females (47%), 112 patients with childhood-onset craniopharyngioma (50%), 3153 person-years of follow-up). Excess morbidity and mortality were analysed using standardized incidence and mortality ratios (SIRs and SMRs). Risk factors were evaluated univariably by comparing SIRs and SMRs between non-overlapping subgroups.

Results

Patients with craniopharyngioma experienced excess morbidity due to type 2 diabetes mellitus (T2DM) (SIR: 4.4, 95% confidence interval (CI): 2.8–6.8) and cerebral infarction (SIR: 4.9, 95% CI: 3.1–8.0) compared to the general population. Risks for malignant neoplasms, myocardial infarctions and fractures were not increased. Patients with craniopharyngioma also had excessive total mortality (SMR: 2.7, 95% CI: 2.0–3.8), and mortality due to circulatory (SMR: 2.3, 95% CI: 1.1–4.5) and respiratory (SMR: 6.0, 95% CI: 2.5–14.5) diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence were identified as risk factors for excess T2DM, cerebral infarction and total mortality.

Conclusions

Patients with craniopharyngioma are at an increased risk for T2DM, cerebral infarction, total mortality and mortality due to circulatory and respiratory diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence are important risk factors.

http://ift.tt/2iqYc33