bluuebunny/crossref_metadata_2025 huggingface dataset:
Mimivirus encodes a multifunctional primase with DNA/RNA polymerase, terminal transferase and translesion synthesis activities
Authors: Gupta Ankita , Lad Shailesh B , Ghodke Pratibha P , Pradeepkumar P I , Kondabagil Kiran
Published: April 2019

Acanthamoeba polyphaga mimivirus is an amoeba-infecting giant virus with over 1000 genes including several involved in DNA replication and repair. Here, we report the biochemical characterization of gene product 577 (gp577), a hypothetical protein (product of L537 gene) encoded by mimivirus. Sequence analysis and phylogeny suggested gp577 to be a primase-polymerase (PrimPol)—the first PrimPol to be identified in a nucleocytoplasmic large DNA virus (NCLDV). Recombinant gp577 protein purified as a homodimer and exhibited de novo RNA as well as DNA synthesis on circular and linear single-stranded DNA templates. Further, gp577 extends a DNA/RNA primer annealed to a DNA or RNA template using deoxyribonucleoties (dNTPs) or ribonucleotides (NTPs) demonstrating its DNA/RNA polymerase and reverse transcriptase activity. We also show that gp577 possesses terminal transferase activity and is capable of extending ssDNA and dsDNA with NTPs and dNTPs. Mutation of the conserved primase motif residues of gp577 resulted in the loss of primase, polymerase, reverse transcriptase and terminal transferase activities. Additionally, we show that gp577 possesses translesion synthesis (TLS) activity. Mimiviral gp577 represents the first protein from an NCLDV endowed with primase, polymerase, reverse transcriptase, terminal transferase and TLS activities.
The PSIPRED Protein Analysis Workbench: 20 years on
Authors: Buchan Daniel W A , Jones David T
Published: April 2019

The PSIPRED Workbench is a web server offering a range of predictive methods to the bioscience community for 20 years. Here, we present the work we have completed to update the PSIPRED Protein Analysis Workbench and make it ready for the next 20 years. The main focus of our recent website upgrade work has been the acceleration of analyses in the face of increasing protein sequence database size. We additionally discuss any new software, the new hardware infrastructure, our webservices and web site. Lastly we survey updates to some of the key predictive algorithms available through our website.
Nephrology and Public Policy Committee propositions to stimulate research collaboration in adults and children in Europe
Authors: Massy Ziad A , Caskey Fergus J , Finne Patrik , Harambat Jerome , Jager Kitty J , Nagler Evi , Stengel Benedicte , Sever Mehmet Sukru , Vanholder Raymond , Blankestijn Peter J , Bruchfeld Annette , Capasso Giovambattista , Fliser Danilo , Fouque Denis , Goumenos Dimitrios , Soler Maria Jose , Rychlík Ivan , Spasovski Goce , Stevens Kathryn , Wanner Christoph , Zoccali Carmine
Published: April 2019

The strengths and the limitations of research activities currently present in Europe are explored in order to outline how to proceed in the near future. Epidemiological and clinical research and public policy in Europe are generally considered to be comprehensive and successful, and the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) is playing a key role in the field of nephrology research. The Nephrology and Public Policy Committee (NPPC) aims to improve the current situation and translation into public policy by planning eight research topics to be supported in the coming 5 years by ERA-EDTA.
Epidemiology of neonatal stroke: A population-based study
Authors: Clive Breanna , Vincer Michael , Ahmad Tahani , Khan Naeem , Afifi Jehier , El-Naggar Walid
Published: April 2019

Objective

The goal of this study was to obtain population-based data on the incidence, clinical presentation, management, imaging features, and long-term outcomes of patients with all types of neonatal stroke (NS).

Methods

Full-term neonates with NS born between January 2007 and December 2013 were identified through the Nova Scotia Provincial Perinatal Follow-up Program Database. Perinatal data and neonatal course were reviewed. Neurodevelopmental outcomes were assessed at 18 and 36 months of age using standardized testing.

Results

Twenty-nine neonates with NS were identified during the study period, giving an incidence of 47 per 100,000 live births in Nova Scotia. Arterial ischemic stroke was the most common stroke type (76%), followed by neonatal hemorrhagic stroke (17%), then cerebral sinovenous thrombosis (7%). The majority of neonates presented with seizures (86%) on the first day of life (76%). At 36 months of age, 23 (79%) of the children had a normal outcome, while 3 (10%) were diagnosed with cerebral palsy (2 with neonatal arterial stroke and one with neonatal hemorrhagic stroke) and 3 (10%) had recurrent seizures (1 patient from each stroke subtype group).

Conclusion

The incidence of NS in Nova Scotia is higher than what has been reported internationally in the literature. However, the neurodevelopmental outcomes at 3 years of age are better. Further studies are required to better understand the reasons for these findings.
CHANGES OF ABSORBED DOSE RATE IN AIR BY CAR-BORNE SURVEY IN NAMIE TOWN, FUKUSHIMA PREFECTURE AFTER THE FUKUSHIMA DAIICHI NUCLEAR POWER PLANT ACCIDENT
Authors: Shiroma Y , Hosoda M , Iwaoka K , Hegedűs M , Kudo H , Tsujiguchi T , Yamaguchi M , Akata N , Kashiwakura I , Tokonami S
Published: April 2019

The latest car-borne survey was carried out by Hirosaki University in order to grasp the local distribution of the absorbed dose rate in air after the evacuation order was lifted on Namie Town in 2017. The car-borne survey of absorbed dose rate in air was carried out on most of the roads which were accessible by car in Namie Town using a 3-in × 3-in NaI(Tl) scintillation spectrometer. The range of the absorbed dose rate in air was calculated to be 0.041–11 μGy h−1. The distribution maps of the absorbed dose rate in air were drawn based on the data obtained during the surveys in 2011, 2015 and 2017. The comparison of these absorbed dose rates in air suggests that the elevated absorbed dose rate in air in Namie Town caused by the FDNPP accident may be decreasing faster than natural decline which includes weathering effect and physical decay due to the artificial decontamination.
A-107 A general description of the HTLV-1 Cohort at the Institute of Tropical Medicine Alexander von Humboldt (1989–2015)
Authors: Gotuzzo Eduardo , González Elsa , Mejía Fernando , Ramos Yessica , Alvarez Carolina , Verdonck Kristien
Published: April 2019

In Peru, the Institute of Tropical Medicine Alexander von Humboldt, in partnership with Hospital Cayetano Heredia, promotes specialized care for persons with HTLV-1 infection since 1989. Briefly, we offer pre and post-test counseling, diagnostic services, and medical attention. People are eligible for diagnostic services if they have: a prior seropositive result in Blood Banks; a first-degree relative or sexual partner with HTLV-1 infection; a potential diagnosis of HTLV-1-associated diseases (mainly: HTLV-1-associated myelopathy (HAM/TSP), Strongyloides stercoralis (SS) infection, T-cell leukemia/lymphoma, uveitis, infective dermatitis). Given the limited capacity to continuously afford confirmatory testing, HTLV infection is also diagnosed with repeatedly reactive ELISA tests. Cases receive post-test counseling, and specialized medical services. This setting has promoted our HTLV-1 Cohort; for those consenting, enrollment is at time of HTLV-1 testing.

Until June 2015, 8845 persons were enrolled in the cohort; the median age was 38.8 years (interquartile range: 26.5–52.3), 5042 (57.5%) were women and 4337 (49.0%) did not report being related to someone with HTLV-1 infection and were thus defined as index cases. The leading reasons for HTLV testing were family studies (3987, 45.1%), followed by potential diagnosis of HTLV-1 associated diseases (3365, 38.0%), and seropositive results in Blood Banks (718, 8.5%).

HTLV infection was diagnosed in 3359 persons (48.0%), including 1202 (13.6%) with available confirmatory testing. Most (58.3%) were women; the median age was 43 years (IQR: 31.0–55.6), but 285 were children. The proportion of HTLV diagnosis varied by reason for testing: 79.0% for those with potential HAM/TPS, 69.8% for potential ATL, 31.0% in cases with SS; 79.0% in donors and 34.0% when testing was done as part of family studies. At entry, the cases with HTLV infection included potential HAM/TSP (621, 18.5%); other complications mostly of infectious nature (338, 10.1%); SS infection (238, 7.0%), and ATL (5.6%).

Most cases (1426, 43.0%) were lost to follow-up in the first year after diagnosis; in those remaining, with 8227 person-years of follow-up up to December 31, 2016, there were 88 incident cases of HAM/TSP, 47 of SS, and 8 of ATL. In those not lost-to-follow-up, 113 out of 1933 (5.6%) died.

Our cohort offers a valuable platform to increase the quality of evidence regarding clinical consequences of HTLV-1 infection; at the same time, the number of pediatric cases remark the imperative need to implement sound actions for prevention of transmission of HTLV-1 from mother-to-child.
F-102 Antivirals, a lot has been achieved, yet a long way to go
Authors: Neyts Johan
Published: April 2019

Today, small molecule antiviral drugs are available for the treatment of infections with herpesviruses, HIV, HBV and HCV as well as with influenza viruses. Yet, for many other viruses that cause life-threatening infections and many of which are considered emerging and/or neglected pathogens, there are no drugs available. I will discuss our efforts to develop potent antivirals against flaviviruses (such as dengue), alphaviruses (such as chikungunya) and enteroviruses as well as against the hepatitis E and the rabies virus. Several excellent molecular targets for the selective inhibition of viral replication (and that have remained largely unexplored) have been identified, such as the non-structural protein NS4B of flaviviruses, the capping machinery of alphaviruses and the 2C helicase of enteroviruses. Besides the development of antiviral strategies, our team is also developing novel vaccines. More in particular we developed the PLLAV (Plasmid Launched Live Attenuated Virus) vaccine technology platform. Simple administration (mice, hamsters, NHP and pigs) of a PLLAV-plasmid that carries the entire coding sequence of the yellow fever 17D vaccine virus, results in the efficient vaccination. Next we demonstrate that foreign sequences can be inserted in the YFV-17D sequence, thus resulting in, for example, dual vaccine candidates against either the yellow fever and the rabies virus or the yellow fever and the Lassa fever virus. The PLLAV technology allows to rapidly produce using a straightforward fermentation process thermostable alternatives for live attenuated viral vaccines.

www.antivirals.be
www.facebook.com/NeytsLab
F-104 Emergence of novel EV-D68 lineages associated with acute flaccid paralysis
Authors: Scheuermann Richard H.
Published: April 2019

Enterovirus D68 (EV-D68) has historically been associated with respiratory illnesses. However, in the summers of 2014 and 2016, EV-D68 outbreaks coincided with a spike in polio-like acute flaccid myelitis/paralysis (AFM/AFP) cases. This raised concerns that EV-D68 could be the causative agent of AFM during these recent outbreaks. To assess the potential neurotropism of EV-D68, we utilized the neuroblastoma-derived neuronal cell line SH-SY5Y as a cell culture model to determine if differential infection is observed for different EV-D68 strains. In contrast to HeLa and A549 cells, which support viral infection of all EV-D68 strains tested, SH-SY5Y cells only supported infection by a subset of contemporary EV-D68 strains, including isolates from the 2014 outbreak. Viral replication and infectivity in SH-SY5Y were assessed using multiple assays: virus production, cytopathic effects, cellular ATP release, and VP1 capsid protein production. Similar differential neurotropism was also observed in differentiated SH-SY5Y cells, primary human neuron cultures, and a mouse paralysis model. Using the SH-SY5Y cell culture model, we determined that barriers to viral binding and entry were at least partly responsible for the differential infectivity phenotype. Transfection of genomic RNA into SH-SY5Y generated virions for all EV-D68 isolates, but only a single round of replication was observed from strains that could not directly infect SH-SY5Y. In addition to supporting virus replication and other functional studies, this cell culture model may help identify the signatures of virulence to confirm epidemiological associations between EV-D68 strains and AFM and allow for the rapid identification and characterization of emerging neurotropic strains.
H-103 Clinical landscape of adult T-cell leukemia: Its impacts on hematology, virology, and immunology
Authors: Matsuoka Masao
Published: April 2019

Prof. Takatsuki and his colleagues reported adult T-cell leukemia (ATL) as the distinct clinical entity based on the clinical features including the presence of leukemic cells with characteristic nuclear shape (flower cells), skin lesion, hypercalcemia and frequent opportunistic infections, and mature T-cell immunophenotyped (Uchiyama T, et al, Blood, 1977). Importantly, they already predicted that ATL is caused by the pathogen since the birth places of ATL patients accumulated in the southwestern Japan (Kyushu and Okinawa). In 1980, Prof. Gallo and his colleagues reported the first human retrovirus, human T-cell leukemia virus (HTLV), from a patient with cutaneous T-cell lymphoma who was later diagnosed as ATL. Thereafter, it was established that HTLV causes ATL. Since Prof. Gallo found another human retrovirus, the first human retrovirus was named human T-cell leukemia virus type 1 (HTLV-1).

Detection of anti-HTV-1 antibody enables us to identify HTLV infected individuals, which discloses unique distribution of HTLV-1carriers in Japan and the world. In addition, serological studies disclosed clinical landscape of ATL. Based on clinical features, ATL is classified to 4 clinical subtypes: acute, chronic, lymphoma-type and smoldering types (Yamguchi K, et al, Blood, 1983). In addition, the familial clustering of ATL cases was prominent, suggesting that genetic or virological factors are involved in development of ATL. Serological analyses found that HTLV-1 mainly transmits from male to female in horizontal transmission. Another clinical feature of ATL is the frequent spontaneous remission, which suggests immunological mechanism.

Early studies of HTLV-1 focused on Tax, which not only transactivates viral genes transcription from the plus strand, but also influences cellular genes. However, Prof. Takatsuki's group thought that clinical ATL samples contain clue of leukemogenic mechanisms by HTLV-1. We found that Tax was not expressed in half of ATL cases, and 3 mechanisms of inactivation of Tax expression: deletion of 5′ long terminal repeat (LTR), DNA methylation of 5′LTR, and genetic changes of the tax gene (nonsense mutation, deletion and insertion), indicating that Tax is not necessary for maintenance of ATL (Tamiya S, et al, Blood, 1996). However, pX region and 3′LTR remain intact in all ATL cases, indicating that this region is critical for ATL. Thereafter, we showed that HTLV-1 bZIP factor (HBZ), which is encoded by the minus strand, plays critical roles for pathogenesis by HTLV-1.

ATL is the first human disease caused by retrovirus. Tremendous efforts on HTLV-1 research by many researchers contribute to studies of next human retrovirus, human immunodeficiency virus (HIV). Thus, discovery of ATL in association with identification of causative human retrovirus leads to great contribution to medical science.
I-101 Quaternary contact improves the potency of broadly neutralizing antibodies to the CD4-binding site of HIV-1
Authors: Lusso Paolo , Liu Qingbo , Lai Yen-Ting , Louder Mark , Kwong Peter D. , Mascola John R
Published: April 2019

Broadly neutralizing antibodies (bNAb) directly cloned from HIV-infected individuals are attracting increasing consideration for the prevention and treatment of HIV-1 infection. We recently reported the identification of a second, quaternary CD4-binding site (CD4-BS) in the native HIV-1 envelope trimer, showing that selected anti-CD4BS NAbs also establish quaternary interactions with a neighboring gp120 protomer through the extended framework 3 (FR3) loop of their heavy chain. In contrast, some potent bNAbs like VRC01 and N6 contain a shorter FR3 loop and appear to interact with a single gp120 protomer. Here, we used structure-based engineering to engraft the extended FR3 loop of VRC03 onto 4 potent anti-CD4 supersite antibodies, namely, VRC01, VRC07, N6 and 3BNC117, with the aim of enabling them to contact an adjacent gp120 promoter. With the exception of 3BNC117, all the chimeric antibodies showed an enhanced neutralizing capacity against the majority of a large HIV-1 envelope panel (208 strains), which correlated with an increased binding affinity for the pre-fusion envelope trimer. The crystal structure of one engineered antibody, N6 FR3-03, was solved in complex with a soluble stabilized trimer, BG505 SOSIP.664, which allowed to visualize the quaternary interaction of the engrafted FR3 loop with residues at the base of the V3 loop of a neighboring gp120 protomer. Thus, engraftment of the VRC03 FR3 loop enabled potent anti-CD4BS antibodies to establish quaternary contact with a neighboring protomer of the HIV-1 Env timer, leading to increased neutralization potency. FR3 loop-chimeric bNAbs may be considered for applications in HIV-1 prevention and treatment.
PC-6 Cardiac morbidity in HIV is associated with checkpoint inhibitor LAG-3
Authors: Pahwa Rajendra , Pallikkuth Suresh , Kausalya Bagavathi , Saravanan Shanmugam , Kumarasamy Nagalingesawaran , Pahwa Savita
Published: April 2019

Background:

Cardiovascular disease (CVD) is a major contributor to mortality and morbidity in HIV infection. The impact of viral suppression with combination antiretroviral therapy and underlying pathophysiologic mechanisms are under investigation. Elevated expression of certain checkpoint inhibitor (CPI) molecules (eg, PD-1, TIGIT, LAG3, TIM3) on T cells is associated with dampened immunity. Recent evidence for expression of receptors for CPI at the tissue level with selective enrichment of LAG3 receptors in the heart point to a control mechanism for organ immune homeostasis (Rev Immunity 44, 2016). This study was aimed at defining the relationship of CPI molecules on immune cells and CVD in HIV infection in a low resource setting.

Methods:

Study participants were recruited in YRG CARE, a tertiary care HIV service provider in Chennai, India. ART naive viremic (Gp1, n = 102) and ART experienced aviremic (Gp2, n = 172) were compared to healthy volunteers (Gp3, n = 64) in a cross-sectional analysis of cardiac function and immunologic markers including CPI molecules on CD4 and CD8 T cells.

Results:

In Gp1 findings of CVD were significant (Mann-Whitney’ U test) for lower cardiac ejection time, stroke volume, stroke volume index, cardiac output and small arterial elasticity with higher systemic vascular resistance compared to Gp2 and Gp3 respectively. Large arterial elasticity was lower in comparison to Gp2. Immune activation and inflammatory cytokines were maximally altered in Gp1. Frequencies of CPI molecules showed differences among the groups, with higher frequencies of CD4+ T cells expressing LAG3 and PD1 in Gp1 compared to GPs 2 and 3, while TIGIT and TIM3 did not differ significantly among the groups (LAG3 Gp1: 4.9 ± 3.4; Gp2: 2.5 ± 1.5; Gp3: 2.4 ± 1.3; PD1 Gp1: 6.2 ± 7.3; Gp2: 1.5 ± 2.5; Gp3: 0.9 ± 1.6; TIGIT Gp1: 34.2 ± 14.9; Gp2: 33.5 ± 11.8; Gp3: 30.1 ± 7.8 and Tim3 Gp1: 1.7 ± 2.7; Gp2: 1.3 ± 1; Gp3: 1.3 ± 0.9). Frequencies of CD4+ T cells positive for LAG3, PD1, and for dual expression of LAG3 plus PD1 were inversely correlated with cardiac ejection time, cardiac output, cardiac index, stroke volume, stroke volume index and systemic vascular resistance in Gp1 and with large artery elasticity, and except for PD1, also with small artery elasticity in Gp2.

Conclusions:

In ART naive HIV subjects continuous antigenic stimulation of the immune system results in upregulation of multiple CPI molecules in association with immune activation. Our finding of the association of LAG3 and PD1 expressing CD4 cells in cardiac morbidity points to a dominant role of these pathways in regulating cardiac health, given that LAG3 receptors are enriched at the tissue level in the heart. Investigations to understand the immune mechanisms involved could provide insight into potential role of LAG3 immunotherapy (which is in early clinical trials in cancer) in prevention or treatment of cardiac dysfunction in HIV.
Molecular Biology of Opioid Analgesia and Its Clinical Considerations
Authors: Finkel Julia C. , Pukish Jennifer
Published: April 2019

Understanding the molecular biology of opioid analgesia is essential for its proper implementation and mechanistic approach to its modulation in order to maximize analgesia and minimize undesired effects. By appreciating the molecular mechanisms intrinsic to opioid analgesia, one can manipulate a molecular target to augment or diminish a specific effect using adjuvant drugs, select an appropriate opioid for opioid rotation or define a molecular target for new opioid drug development. In this review, we present the cellular and molecular mechanisms of opioid analgesia and that of the associated phenomena of tolerance, dependence, and hyperalgesia. The specific mechanisms highlighted are those that presently can be clinically addressed.
Application of the New Centers for Disease Control and Prevention Surveillance Criteria for Ventilator-Associated Events to a Cohort of PICU Patients Identifies Different Patients Compared With the Previous Definition and Physician Diagnosis*
Authors: Ziegler Katherine M. , Haywood Jonathan D. , Sontag Marci K. , Mourani Peter M.
Published: April 2019

Objectives:

We sought to compare the performance of the 2008 Centers for Disease Control and Prevention Pediatric criteria for ventilator-associated pneumonia, the 2013 Adult Ventilator-Associated Condition criteria, the new Draft Pediatric Ventilator-Associated Condition criteria, and physician-diagnosed ventilator-associated pneumonia in a cohort of PICU patients.

Design:

Secondary analysis of a previously conducted prospective observational study.

Setting:

PICU within a tertiary care children’s hospital between April 1, 2010, and April 1, 2011.

Patients:

Patients between 31 days and 18 years old, mechanically ventilated via endotracheal tube for more than 72 hours and no limitations of care.

Interventions:

None.

Measurements and Main Results:

Ventilator-associated pneumonia criteria applied in real time and ventilator-associated condition criteria applied retrospectively. Outcomes assessed between cases and noncases within criteria. Of the 133 eligible participants, 24 (18%) had ventilator-associated pneumonia by 2008 Pediatric criteria and 27 (20%) by physician diagnosis. Sixteen (12%) and 10 (8%) had ventilator-associated condition by 2013 Adult and Draft Pediatric criteria, respectively. We found significant overlap between cases identified with 2008 Pediatric criteria and physician diagnosis (p = 0.549), but comparisons between the other definitions revealed that the newer criteria identify different patients than previous Centers for Disease Control and Prevention ventilator-associated pneumonia criteria and physician diagnosis (p < 0.01). Although 20 participants were diagnosed with ventilator-associated pneumonia by 2008 Pediatric criteria and physician diagnosis, only three participants were identified by all four criteria. Three subjects uniquely identified by the Draft Pediatric criteria were noninfectious in etiology. Cases identified by all criteria except Draft Pediatric had higher ratios of actual ICU length of stay to Pediatric Risk of Mortality III-adjusted expected length of stay compared with noncases.

Conclusions:

The Draft Pediatric criteria identify fewer and different patients than previous ventilator-associated pneumonia criteria or physician diagnosis, potentially missing patients with preventable harms, but also identified patients with potentially preventable noninfectious respiratory deteriorations. Further investigations are required to maximize the identification of patients with preventable harms from mechanical ventilation.
Complex Lower Extremity Wound in the Complex Host: Results From a Multicenter Registry
Authors: Kim Paul J. , Attinger Christopher E. , Orgill Dennis , Galiano Robert D. , Steinberg John S. , Evans Karen K. , Lavery Lawrence A.
Published: April 2019

Background:

The complex diabetic lower extremity wound has not been well studied. There are a variety of new technologies now being applied with a paucity of evidence in evaluating their outcomes. The aim of this study is to describe clinical outcomes in the complex lower extremity wound in the comorbid host. We hypothesized that treatment choice would have minimal impact on healing outcomes in this compromised population.

Methods:

A multicenter retrospective registry of patients with diabetes and lower extremity wounds was created to compare treatment modalities of collagen–glycosaminoglycan scaffold, negative-pressure wound therapy, local tissue flap, and free tissue transfer. Statistical analyses included descriptive, proportional comparisons and Cox regression.

Results:

There were no statistical differences in age, hemoglobin A1c, or body mass index between groups. Study patients had a history of amputation (40.5%), peripheral vascular disease (54.6%), peripheral neuropathy (64.8%), end-stage renal disease (13.9%), renal/hepatic disease (40.4%), and hypertension (85%). The most common wound etiologies were surgical dehiscence (69%), diabetic neuropathic wounds (39%), and ischemic wounds (28%), most commonly located on the foot or at a prior amputation site (30%). Mean wound area was 57.9 cm2 and almost half with exposed bone. There were no statistical differences between treatment groups in proportion or time to healing, recurrence, or time to return to baseline function.

Conclusions:

Commonly used treatment modalities employed for this population of patients resulted in similar outcomes. This is the first study to describe the complex diabetic lower extremity wound in a complex host.
Retromuscular Mesh Repair Using Fibrin Glue: Early Outcomes and Cost-effectiveness of an Evolving Technique
Authors: Rhemtulla Irfan A. , Tecce Michael G. , Broach Robyn B. , Messa Charles A. , Mauch Jaclyn T. , Fischer John P.
Published: April 2019

Background:

Retromuscular hernia repairs (RHRs) decrease hernia recurrence and surgical site infections but can cause significant pain. We aimed to determine if pain and postoperative outcomes differed when comparing suture fixation (SF) of mesh to fibrin glue fixation (FGF).

Methods:

Patients undergoing RHR (n = 87) between December 1, 2015 and December 31, 2017 were retrospectively identified. Patients received SF of mesh (n = 59, 67.8%) before the senior author changing his technique to FGF (n = 28, 32.2%). These 2 cohorts were matched (age, body mass index, number of prior repairs, mesh type, defect size, and wound class). Outcomes were analyzed using a matched pairs design with multivariable linear regression.

Results:

Two matched groups (21 FGF and 21 SF) were analyzed (45.2% female, average age 56 years, average body mass index 34.7 kg/m2, and average defect size 330 cm2). Statistical significance was observed for FGF compared with SF: length of stay (3.7 versus 7.1 days, P = 0.032), time with a drain (17.2 versus 27.5 days, P = 0.012), 30-day postoperative visits (2 versus 3, P = 0.003), pain scores (5.2 versus 3.1, P = 0.019) and activity within the first 24 hours (walking versus sitting, P = 0.002). Operative time decreased by 23.1 minutes (P = 0.352) and postoperative narcotic represcription (3 versus. 8 patients, p=0.147) also decreased. Average cost for patients receiving SF was $36,152 compared to $21,782 for FGF (P = 0.035).

Conclusions:

Sutureless RHR using FGF may result in decreased pain when compared with a matched cohort receiving SF, translating to enhanced recovery time, shortened hospital stay, and decreased costs.
Contemporary Management of Unexplained Infertility
Authors: STEWART JOSHUA D. , PASTERNAK MONICA C. , PEREIRA NIGEL , ROSENWAKS ZEV
Published: April 2019

Infertility is estimated to affect about 10% to 15% of couples. Most cases of infertility have etiologies that can be attributed to tubal factors, ovulatory dysfunction, endometriosis, uterine factor, male factor, or diminished ovarian reserve, while the remainder often do not have a known attributable cause, that is, unexplained infertility. The current manuscript summarizes the contemporary management of unexplained infertility.
Long-Term Descemetocele Management With Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) Treatment
Authors: Xu Mimi , Randleman James B. , Chiu Gloria B.
Published: April 2019

Purpose:

To report a patient with chronic ocular graft versus host disease who achieved long-term stability of a descemetocele using prosthetic replacement of the ocular surface ecosystem (PROSE) treatment.

Methods:

Case report and literature review.

Results:

A 60-year-old white man, who underwent PROSE treatment 4 years earlier to address severe dry eyes secondary to ocular graft versus host disease, developed a central corneal ulcer that resulted in descemetocele formation. Because of the risks of surgical intervention in an immunocompromised patient with severe ocular surface disease, the descemetocele was monitored closely as the patient continued PROSE device wear. After 1 year with continued PROSE therapy, the patient's descemetocele remained stable without perforation and corrected visual acuity stabilized at 20/50 in the affected eye.

Conclusions:

This is the first case that reports stabilization of a descemetocele with a PROSE device. For patients at high risk for postsurgical complications, PROSE treatment could be considered as an alternative to corneal transplantation and as an adjunct to other ocular therapies in patients with descemetocele formation.
Two Soft Contact Lenses Retained in the Superior Fornix for 15 Years in a Patient With Unique Orbital Anatomy
Authors: Holicki Cameron , Sims Jake , Holicki Joseph
Published: April 2019

A 70-year-old white woman presented to her ophthalmologist with bacterial conjunctivitis resistant to treatment. The relationship between the patient's globe and superior orbital rim prompted high clinical suspicion of an occult foreign body as the cause. The following article describes the office visits preceding the discovery of two adhered soft contact lenses lodged in the superior fornix of the right eye that had been hidden for 15 years. We discuss the role her unique orbital anatomy played in successfully concealing these foreign bodies for over a decade. In addition, we present an algorithm to practice when an occult foreign body is suspected, which includes effective clinical techniques.
A Successful Application of Intraventricular and Intravenous Colistin for Extensively Drug-Resistant Acinetobacter baumannii Ventriculitis in a Neurosurgical Patient Undergoing Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome
Authors: Lapinskienė Indrė , Linkaitė Gabrielė , Remeikaitė Donata , Balčiūnas Lukas , Kvaščevičius Robertas , Kšanas Ugnius , Šipylaitė Jūratė , Šerpytis Mindaugas
Published: April 2019

The prevalence of extensively drug-resistant Acinetobacter baumannii neuroinfection has markedly increased, and this infection is now a first-line medical emergency worldwide with a mortality rate of up to 50%. Its expanding resistance to most intravenous antibiotic treatments, as well as the severity of the initiated condition, obligates practitioners to concentrate on today's most effective therapy—the combination of intravenous and intraventricular/intrathecal colistin. The specific characteristics of the intraventricular/intrathecal route are promising for patients with supportive mechanical devices, such as extracorporeal membrane oxygenation or hemodiafiltration, which have significant impacts on drug pharmacokinetics in the blood. This influence is minimized when antibiotics are administered directly into cerebrospinal fluid. The case report represents a history of a 39-year-old man with nosocomial carbapenem-resistant A. baumannii ventriculitis and acute respiratory distress syndrome. His treatment with intravenous and intraventricular colistin, as well as extracorporeal membrane oxygenation therapy, managed to succeed in helping the patient's recovery.
Disseminated Leishmaniasis With Immune Reconstitution Inflammatory Syndrome–associated Pneumocystis Pneumonia in a Human Immunodeficiency Virus–infected Patient With First-line Antiretroviral Therapy Failure
Authors: Gupta Pulin Kumar , Mahto Subodh Kumar , Mittal Abhishek , Chawla Mahinder Pal S. , Kaushal Manju , Kumar Arvind
Published: April 2019

Disseminated atypical leishmaniasis is a stage IV defining illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Although visceral leishmaniasis is endemic in some regions of India, atypical disseminated leishmaniasis is not reported frequently. Patients of visceral leishmaniasis in HIV/acquired immunodeficiency syndrome present with atypical manifestations like involvement of upper or lower gastrointestinal tract, lungs, pleura, liver, kidney, skin, and peritoneum and have chronic progression with relapses irrespective of treatment given. We hereby report a case of atypical disseminated leishmaniasis in an HIV-positive patient, who also developed Pneumocystis pneumonia as a part of immune reconstitution syndrome after failure of first-line antiretroviral therapy. Our patient also had involvement of gastrointestinal tract and lymph nodes which has rarely been reported from Indian subcontinent.
Thyroid Incidentaloma on 18F-fluorocholine PET/CT and 68Ga-PSMA PET/CT Revealing a Medullary Thyroid Carcinoma
Authors: Ciappuccini Renaud , Edet-Sanson Agathe , Saguet-Rysanek Virginie , Gauthé Mathieu , Bardet Stéphane
Published: April 2019

A 66-year-old man with prostate cancer underwent 18F-fluorocholine PET/CT and thereafter 68Ga-labeled prostate-specific membrane antigen PET/CT to explore a rising prostate-specific antigen level. Both PET/CT studies showed a thyroid incidentaloma of the right lobe. Neck ultrasound confirmed the presence of a 16-mm right thyroid nodule. The serum calcitonin level was moderately increased at 25 ng/mL (<10). Cytology was non-diagnostic (Bethesda I). A right lobectomy was performed and pathology revealed a 15-mm medullary thyroid cancer. Two months after surgery, the calcitonin level returned to normal at 3.3 ng/mL.
68Ga DOTATATE PET/CT Versus 18F-FDG PET/CT for Detecting Intramedullary Hemangioblastoma in a Patient With Von Hippel-Lindau Disease
Authors: Banezhad Farnaz , Kiamanesh Zahra , Emami Farshad , Sadeghi Ramin
Published: April 2019

Von Hippel-Lindau disease is an inherited syndrome associated with several benign and malignant tumors such as central nervous system (CNS) hemangioblastoma. Herein, we report a known case of A Von Hippel-Lindau patient with a cerebral hemangioblastoma who was referred for further evaluation because of recent paraparesis. 18F-FDG PET/CT showed no focal uptake in the thoracic spine, which demonstrated increased 68Ga DOTATATE activity, owing to overexpression of somatostatin receptors, suggesting spinal cord hemangioblastoma. This case report indicates the significant role of 68Ga-labeled somatostatin receptor analogs in the diagnosis of hemangioblastoma.
Postchemotherapy Histiocyte-Rich Pseudotumor of the Spleen Simulating Residual Disease in a Patient With Non-Hodgkin Lymphoma on FDG PET/CT
Authors: Hod Nir , Lantsberg Sophie , Anconina Reut , Levin Daniel , Nalbandyan Karen , Levi Itai
Published: April 2019

A 64-year-old man was treated with multiagent chemotherapy owing to high-grade non-Hodgkin lymphoma presenting as a bulky disease involving the spleen. Interim and posttreatment sequential FDG PET/CT scans revealed a residual splenic mass showing markedly intense FDG uptake suspected of a residual viable lymphoma. To definitely decide about the appropriate treatment, a laparoscopic splenectomy was performed. Histopathologic specimen was compatible with the rare diagnosis of postchemotherapy histiocyte-rich pseudotumor of the spleen, a potential pitfall simulating viable disease on FDG PET/CT.
Avid 68Ga-PSMA Uptake in Accessory Submandibular Salivary Gland
Authors: Zhang Wei , Zhang Li , Zhao Yanhong , Chen Yue
Published: April 2019

Accessory submandibular salivary gland (ASSG) is an extremely rare variation of the submandibular salivary gland. We reported a 65-year-old man with prostate cancer underwent 68Ga-PSMA PET/CT for active surveillance. The images showed abnormal PSMA uptake adjacent to the submandibular salivary gland without abnormal activity distribution in the rest regions of the body. The lesion density was similar to that of the submandibular salivary gland. Pathological biopsy confirmed that it was an ASSG. Our case illustrates that ASSG is an addition benign cause of extraprostatic uptake of PSMA.
18F-FDG PET/CT in a Case of Metastatic Breast Cancer to the Vulva
Authors: Guglielmo Priscilla , Paderno Mariachiara , Elisei Federica , Guerra Luca , Landoni Claudio , Buda Alessandro , Crivellaro Cinzia
Published: April 2019

A 56-year-old woman, previously treated for breast cancer, presented to gynecologists with a lump of the left labium major of the vulva. The FDG pattern resembled as a cIV stage vulvar cancer, whereas biopsy indicated metastases from breast cancer. Metastatic disease to the vulva is particularly uncommon, representing 5% to 8% of all vulvar cancer lesions. However, gynecological uptakes, including vulvar site, have to be kept in mind as a possible site of metastatic lesions from breast cancer.
68Ga-NOTA-Evans Blue TOF PET/MR Lymphoscintigraphy Evaluation of the Severity of Lower Limb Lymphedema
Authors: Hou Guozhu , Hou Bo , Jiang Yuanyuan , Zhu Zhaohui , Long Xiao , Chen Xiaoyuan , Cheng Wuying
Published: April 2019

Purpose

This study was designed to investigate the role of 68Ga-NOTA-Evans Blue (NEB) time-of-flight (TOF) PET/MR in evaluating lower limb lymphedema by visual analysis and novel parameters.

Methods

Thirteen patients with unilateral lower limb lymphedema were divided into 3 groups according to the clinical severity: minimal (4 patients), moderate (5 patients), and severe (4 patients). All patients underwent 68Ga-NEB TOF PET/MR lymphoscintigraphy. The ratio of the standardized uptake value (SUV) of superficial lymphatic vessel (SLV) versus SUV of deep lymphatic vessel (DVL) (SUVslv/dlv) was designed to assess the level of lymphedema severity. The correlation between lymphedema severity and lymphoscintigraphy findings was determined using 1-way analysis of variance, the t test, and Pearson correlation analysis.

Results

There was a significant difference in the SUVslv between the affected limbs and normal limbs in all subjects (affected limbs: 0.57 ± 0.32, normal limbs: 1.86 ± 1.43; P < 0.05), which was not found in the SUVdlv (affected limbs: 0.64 ± 0.39, normal limbs: 0.63 ± 0.31; P > 0.1). The SUVslv/dlv of the affected limbs showed statistical differences within the 3 groups (P < 0.05) (minimal group: 1.91 ± 0.45; moderate group: 0.84 ± 0.16; severe group: 0.42 ± 0.11). The statistical analysis revealed a negative correlation between SUVslv/dlv and the severity of lymphedema (r = −0.899; P < 0.01).

Conclusions

68Ga-NEB TOF PET/MR lymphoscintigraphy can provide anatomical and functional information of lymphatic vessels to guide surgery plans. SUVslv/dlv was well correlated with clinical lymphedema severity and might be potential in evaluating bilateral lower limb lymphedema.
Cadaveric Bilateral Proximal Forearm Allotransplantation
Authors: Sivakumar Dinesh K. , Chavan Vinayak , Chittoria RaviKumar , Thiruvoth Friji M. , Mohapatra Devi Prasad , Subbarayan Elankumar , Reddy Konda Sireesha , Babu Preethitha , Kumaran Senthil , Aggarwal Abhinav , Guptha Saurabh
Published: April 2019

Until, sometime ago, microsurgery meant mainly covering a defect or replanting severed parts back to where they belong. Now, restoration of original function and aesthetic consideration is a must in planning reconstructive procedure. Hand transplant combines hand surgery and microsurgery with complex multidisciplinary care.

At the anniversary of our first cadaveric bilateral proximal forearm transplantation done in the country's government institute, we would like to share our experience in performing the surgery, outcomes so far, complications, and lessons learned, to contribute to the growing knowledge of vascularized composite allotransplant.
Better understanding the utilization of damage control laparotomy: A multi-institutional quality improvement project
Authors: Harvin John A. , Sharpe John P. , Croce Martin A. , Goodman Michael D. , Pritts Timothy A. , Dauer Elizabeth D. , Moran Benjamin J. , Rodriguez Rachel D. , Zarzaur Ben L. , Kreiner Laura A. , Claridge Jeffrey A. , Holcomb John B.
Published: April 2019

BACKGROUND

Rates of damage control laparotomy (DCL) vary widely and consensus on appropriate indications does not exist. The purposes of this multicenter quality improvement (QI) project were to decrease the use of DCL and to identify indications where consensus exists.

METHODS

In 2016, six US Level I trauma centers performed a yearlong, QI project utilizing a single QI tool: audit and feedback. Each emergent trauma laparotomy was prospectively reviewed. Damage control laparotomy cases were adjudicated based on the majority vote of faculty members as being appropriate or potentially, in retrospect, safe for definitive laparotomy. The rate of DCL for 2 years prior (2014 and 2015) was retrospectively collected and used as a control. To account for secular trends of DCL, interrupted time series was used to effectiveness of the QI interventions.

RESULTS

Eight hundred seventy-two emergent laparotomies were performed: 73% definitive laparotomies, 24% DCLs, and 3% intraoperative deaths. Of the 209 DCLs, 162 (78%) were voted appropriate, and 47 (22%) were voted to have been potentially safe for definitive laparotomy. Rates of DCL ranged from 16% to 34%. Common indications for DCL for which consensus existed were packing (103/115 [90%] appropriate) and hemodynamic instability (33/40 [83%] appropriate). The only common indication for which primary closure at the initial laparotomy could have been safely performed was avoiding a planned second look (16/32 [50%] appropriate).

CONCLUSION

A single faceted QI intervention failed to decrease the rate of DCL at six US Level I trauma centers. However, opportunities for improvement in safely decreasing the rate of DCL were present. Second look laparotomy appears to lack consensus as an indication for DCL and may represent a target to decrease the rate of DCL after injury.

LEVEL OF EVIDENCE

Epidemiological study with one negative criterion, level III.
Defining geographic emergency medical services coverage in trauma systems
Authors: Brown Joshua B. , Rosengart Matthew R. , Peitzman Andrew B. , Billiar Timothy R. , Sperry Jason L.
Published: April 2019

BACKGROUND

Geographic distribution of trauma system resources including trauma centers and helicopter bases correlate with outcomes. However, ground emergency medical services (EMS) coverage is dynamic and more difficult to quantify. Our objective was to evaluate measures that describe ground EMS coverage in trauma systems and correlate with outcome.

METHODS

Trauma system resources in Pennsylvania were mapped. Primary outcome was county age-adjusted transportation injury fatality rate. Measures of county EMS coverage included average distance to the nearest trauma center, number of basic life support and advanced life support units/100 square miles, distance differential between the nearest trauma center and nearest helicopter base, and nearest neighbor ratio (dispersed or clustered geographic pattern of agencies). Spatial-lag regression determined association between fatality rates and these measures, adjusted for prehospital time, Injury Severity Score, and socioeconomic factors. Relative importance of these measures was determined by assessing the loss in R
2 value from the full model by removing each measure. A Geographic Emergency Medical Services Index (GEMSI) was created based on these measures for each county.

RESULTS

Median fatality rate was higher in counties with fewer trauma system resources. Decreasing distance to nearest trauma center, increasing advanced life support units/100 square miles, greater distance reduction due to helicopter bases, and dispersed geographic pattern of county EMS agencies were associated with lower fatality rates. The GEMSI ranged from −6.6 to 16.4 and accounted for 49% of variation in fatality rates. Adding an EMS agency to a single county that produced a dispersed pattern of EMS coverage reduced predicted fatality rate by 6%, while moving a helicopter base into the same county reduced predicted fatality rate by 22%.

CONCLUSION

The GEMSI uses several measures of ground EMS coverage and correlates with outcome. This tool may be used to describe and compare ground EMS coverage across trauma system geographies, as well as help optimize the geographic distribution of trauma system resources.

LEVEL OF EVIDENCE

Ecological study, level IV.
X-ray studies of the transformation from high- to low-density amorphous water
Authors: Mariedahl Daniel , Perakis Fivos , Späh Alexander , Pathak Harshad , Kim Kyung Hwan , Benmore Chris , Nilsson Anders , Amann-Winkel Katrin
Published: April 2019

Here we report about the structural evolution during the conversion from high-density amorphous ices at ambient pressure to the low-density state. Using high-energy X-ray diffraction, we have monitored the transformation by following in reciprocal space the structure factor S
OO
(
Q
) and derived in real space the pair distribution function g
OO
(
r
). Heating equilibrated high-density amorphous ice (eHDA) at a fast rate (4 K min
–1
), the transition to the low-density form occurs very rapidly, while domains of both high- and low-density coexist. On the other hand, the transition in the case of unannealed HDA (uHDA) and very-high-density amorphous ice is more complex and of continuous nature. The direct comparison of eHDA and uHDA indicates that the molecular structure of uHDA contains a larger amount of tetrahedral motives. The different crystallization behaviour of the derived low-density amorphous states is interpreted as emanating from increased tetrahedral coordination present in uHDA.

This article is part of the theme issue ‘The physics and chemistry of ice: scaffolding across scales, from the viability of life to the formation of planets'.