bluuebunny/crossref_metadata_2025 huggingface dataset:
The Leafless Orchid Cymbidium macrorhizon Performs Photosynthesis in the Pericarp during the Fruiting Season
Authors: Kobayashi Koichi , Suetsugu Kenji , Wada Hajime
Published: January 2021

Photosynthesis with highly photoreactive chlorophyll (Chl) provides energy for plant growth but with simultaneous risk of photooxidative damage and photoprotection costs. Although the leafless orchid Cymbidium macrorhizon mostly depends on mycorrhizal fungi for carbon, it accumulates Chl particularly during fruiting and may not be fully mycoheterotrophic. In fact, stable isotopic analysis suggested that the fruiting C. macrorhizon specimens obtain a significant proportion of its carbon demands through photosynthesis. However, actual photosynthetic characteristics of this leafless orchid are unknown. To reveal the functionality of photosynthetic electron transport in C. macrorhizon, we compared its photosynthetic properties with those of its relative mixotrophic orchid Cymbidium goeringii and the model plant Arabidopsis thaliana. Compared with C. goeringii and A. thaliana, maximum photochemical efficiency of PSII was substantially low in C. macrorhizon. Chl fluorescence induction kinetics revealed that the electron transport capacity of PSII was limited in C. macrorhizon. Chl fluorescence analysis at 77 K suggested partial energetic disconnection of the light-harvesting antenna from the PSII reaction center in C. macrorhizon. Despite its low PSII photochemical efficiency, C. macrorhizon showed photosynthetic electron transport activity both in the field and under laboratory conditions. Cymbidium macrorhizon developed strong nonphotochemical quenching in response to increased light intensity as did C. goeringii, suggesting the functionality of photoprotective systems in this orchid. Moreover, C. macrorhizon fruit developed stomata on the pericarp and showed net O2-evolving activity. Our data demonstrate that C. macrorhizon can perform photosynthetic electron transport in the pericarp, although its contribution to net carbon acquisition may be limited.
The Arabidopsis histone demethylase JMJ28 regulates CONSTANS by interacting with FBH transcription factors
Authors: Hung Fu-Yu , Lai You-Cheng , Wang Jianhao , Feng Yun-Ru , Shih Yuan-Hsin , Chen Jian-Hao , Sun Hua-Chung , Yang Songguang , Li Chenlong , Wu Keqiang
Published: January 2021

Arabidopsis thaliana CONSTANS (CO) is an essential transcription factor that promotes flowering by activating the expression of the floral integrator FLOWERING LOCUS T (FT). A number of histone modification enzymes involved in the regulation of flowering have been identified, but the involvement of epigenetic mechanisms in the regulation of the core flowering regulator CO remains unclear. Previous studies have indicated that the transcription factors, FLOWERING BHLH1 (FBH1), FBH2, FBH3, and FBH4, function redundantly to activate the expression of CO. In this study, we found that the KDM3 group H3K9 demethylase JMJ28 interacts with the FBH transcription factors to activate CO by removing the repressive mark H3K9me2. The occupancy of JMJ28 on the CO locus is decreased in the fbh quadruple mutant, suggesting that the binding of JMJ28 is dependent on FBHs. Furthermore, genome-wide occupancy profile analyses indicate that the binding of JMJ28 to the genome overlaps with that of FBH3, indicating a functional association of JMJ28 and FBH3. Together, these results indicate that Arabidopsis JMJ28 functions as a CO activator by interacting with the FBH transcription factors to remove H3K9me2 from the CO locus.
A Systematic Review and Meta-Analysis of Cognitive Performance among People with Chronic Use of Opioids for Chronic Non-Cancer Pain
Authors: Akhurst Jane , Lovell Monica , Peacock Amy , Bruno Raimondo
Published: January 2021

Objective

Opioids, often prescribed for chronic non-cancer pain, may adversely affect cognition. Research has not been synthesized in recent years, during which time academic interest has increased. This study presents meta-analyses on cognitive performance in people taking opioids for chronic non-cancer pain (CNCP).

Methods

We ran systematic literature searches in EMBASE, Medline, and PsycINFO. Eligible studies included people taking opioids for CNCP, an opioid-free group (i.e., case-control) or session (e.g., pre-post), and objective cognitive assessments. Using random-effects meta-analyses, we computed pooled effect sizes for differential task performance for each study design across five domains (motor performance, attention, working memory, executive functions, memory).

Results

Seventeen studies were included. Case-control studies covered three control types (healthy, CNCP, taper-off). Pre-post studies were grouped into five follow-ups (four to six and six to nine weeks; three, six, and 12 months). Effect sizes ranged from 0.02–0.62. Cases showed small magnitude impairments in attention and memory compared with healthy controls. Although limited by small sample sizes, there was no clear evidence of impairment in cases compared with opioid-free controls with CNCP. Cases showed some cognitive improvements from opioid-free baseline to follow-up. Effects were strongest for attention and working memory and were apparent from four weeks to six months follow-up. Other effects were small and nonsignificant.

Conclusions

Opioid therapy for CNCP did not worsen cognitive performance and improved it for some domains. People who take opioids for CNCP may evidence deficits in attention and memory, but this is unlikely to translate to global impairment and likely relates to pain more so than opioids.
Attenuating Treatment-Related Cardiotoxicity in Women Recently Diagnosed With Breast Cancer via a Tailored Therapeutic Exercise Program: Protocol of the ATOPE Trial
Authors: Postigo-Martin Paula , Peñafiel-Burkhardt Rafael , Gallart-Aragón Tania , Alcaide-Lucena Miriam , Artacho-Cordón Francisco , Galiano-Castillo Noelia , Fernández-Lao Carolina , Martín-Martín Lydia , Lozano-Lozano Mario , Ruíz-Vozmediano Julia , Moreno-Gutiérrez Salvador , Illescas-Montes Rebeca , Arroyo-Morales Manuel , Cantarero-Villanueva Irene
Published: January 2021

Objective

Therapeutic exercise is already used to ameliorate some of the side effects of cancer treatment. Recent studies examined its preventive potential regarding treatment-related toxicity, which can increase the risk of functional decline and lead to disease recurrence and death. This trial will examine whether the Tailored Therapeutic Exercise and Recovery Strategies (ATOPE) program, performed before treatment, can mitigate the onset and extent of cardiotoxicity beyond that achieved when the program is followed during treatment in recently diagnosed breast cancer patients.

Methods

The intervention has a preparatory phase plus 12 to 18 sessions of tailored, high-intensity exercise, and post-exercise recovery strategies. A total of 120 women recently diagnosed with breast cancer, at risk of cardiotoxicity due to anticancer treatment awaiting surgery followed by chemotherapy and/or radiotherapy, will be randomized to either group. In a feasibility study, measurements related to recruitment rate, satisfaction with the program, adherence to them, the retention of participants, safety, and adverse effects will be explored. In the main trial, the efficacy of these interventions will be examined. The major outcome will be cardiotoxicity, assessed echocardiographically via the left ventricular ejection fraction. Other clinical, physical, and anthropometric outcomes and biological and hormonal variables will also be assessed after diagnosis, after treatment, 1 year after treatment ends, and 3 years after treatment ends.

Conclusion

Given its potential effect on patient survival, the mitigation of cardiotoxicity is a priority, and physical therapists have an important role in this mitigation. If the ATOPE intervention performed before treatment returns better cardioprotection results, it may be recommendable that patients recently diagnosed follow this program.

Impact

The ATOPE program will highlight the need for a physical therapist intervention from the moment of diagnosis, in the prevention or mitigation of cardiotoxicity, in women with breast cancer. It could help physical therapists to establish an adequate therapeutic exercise dose adapted to breast cancer patients and to propose correct therapeutic exercise prescription according to the assimilation of the sessions.
EVALUATION OF MODEL-BASED ITERATIVE RECONSTRUCTION IN ABDOMINAL COMPUTED TOMOGRAPHY IMAGING AT TWO DIFFERENT DOSE LEVELS
Authors: Hettinger E , Aurumskjöld M-L , Sartor H , Holmquist F , Svärd D , Timberg P
Published: January 2021

The purpose of this study was to qualitatively evaluate recently introduced Model-based iterative reconstruction method (IMR) and routinely used iterative reconstruction algorithm iDose4 to investigate future dose reduction possibilities for abdominal CT exams. The study contained data from 34 patients who underwent abdominal CT in SkåneUniversityHospital Lund, Sweden. A low-dose scan (CTDIvol3.4 mGy) reconstructed with both iDose4 and IMR and a standard-dose scan (CTDIvol 5.3 mG) reconstructed with iDose4 alone were visually graded in ViewDEX v2.0 by four radiologists using modified EU image criteria. The visual grading characteristics analysis for the evaluation comparing iDose4 standard dose with IMR low dose did not show any statistically significant difference in five of six criteria. In one of the criteria, iDose4 was superior to IMR. The result show promising possibilities are introduced for substantial radiation dose reduction (35%) in abdominal CT imaging when replacing iDose4 with IMR. Still, care should be taken when considering the reproduction of adrenal glands.
Long-Term Real-World Effectiveness of Pharmacotherapies for Schizoaffective Disorder
Authors: Lintunen Jonne , Taipale Heidi , Tanskanen Antti , Mittendorfer-Rutz Ellenor , Tiihonen Jari , Lähteenvuo Markku
Published: January 2021

Objective

To investigate the long-term real-world effectiveness of antipsychotics and other psychopharmacotherapies in the treatment of schizoaffective disorder (SCHAFF).

Method

Two nationwide cohorts of SCHAFF patients were identified from Finnish and Swedish registers. Within-individual design was used with stratified Cox regression. The main exposure was use of antipsychotics. Adjunctive pharmacotherapies included mood stabilizers, antidepressants, and benzodiazepines and benzodiazepine-related drugs. The main outcome was hospitalization due to psychosis.

Results

The Finnish cohort included 7655 and the Swedish cohort 7525 patients. Median follow-up time was 11.2 years (IQR 5.6–11.5) in the Finnish and 7.6 years (IQR 3.8–10.3) in the Swedish cohort. Clozapine and long-acting injectable (LAI) antipsychotics were consistently associated with a decreased risk of psychosis hospitalization and treatment failure (psychiatric hospitalization, any change in medication, death) in both cohorts. Quetiapine was not associated with a decreased risk of psychosis hospitalization. Mood stabilizers used in combination with antipsychotics were associated with a decreased risk of psychosis hospitalization (Finnish cohort HR 0.76, 95% CI 0.71–0.81; Swedish cohort HR 0.84, 0.78–0.90) when compared with antipsychotic monotherapy. Combination of antidepressants and antipsychotics was associated with a decreased risk of psychosis hospitalization in the Swedish cohort (HR 0.90, 0.83–0.97) but not in the Finnish cohort (1.00, 0.94–1.07), and benzodiazepine use was associated with an increased risk (Finnish cohort HR 1.07, 1.01–1.14; Swedish cohort 1.21, 1.13–1.30).

Conclusions

Clozapine, LAIs, and combination therapy with mood stabilizers were associated with the best outcome and use of quetiapine and benzodiazepines with the worst outcome in the treatment of SCHAFF.
There Is Life After the UK Clozapine Central Non-Rechallenge Database
Authors: Oloyede Ebenezer , Casetta Cecilia , Dzahini Olubanke , Segev Aviv , Gaughran Fiona , Shergill Sukhi , Mijovic Alek , Helthuis Marinka , Whiskey Eromona , MacCabe James Hunter , Taylor David
Published: January 2021

Background and Aims

In the United Kingdom, patients on clozapine whose hematological parameters fall below certain thresholds are placed on the Central Non-Rechallenge Database (CNRD), meaning that they cannot be prescribed clozapine again except under exceptional circumstances. This practice was discontinued in the United States in 2015 by expanding the hematological monitoring guidelines, allowing more patients to receive clozapine. Our objective was to investigate the implications this policy change would have on clozapine utilization in the United Kingdom.

Methods

This was an observational, retrospective analysis of patients registered on the CNRD in a large mental health trust. The first objective was to compare the number of patients placed on the CNRD under the United Kingdom and the US Food and Drug Administration (FDA) criteria. The second objective was to explore the hematological and clinical outcomes of CNRD patients. The third objective was to investigate the hematological outcomes of patients rechallenged on clozapine after nonrechallengeable status.

Results

One hundred and fifteen patients were placed on CNRD from 2002 to 2019, of whom 7 (6%) met the equivalent criteria for clozapine discontinuation under the FDA guidelines. Clinical outcomes, as measured by the Clinical Global Impression-Severity scale, were worse 3 months after clozapine cessation than on clozapine (t = −7.4862; P < .001). Sixty-two (54%) patients placed on CNRD were rechallenged. Fifty-nine of those (95%) were successfully rechallenged; 3 patients were placed back on CNRD, only one of which would have had to stop clozapine again under FDA criteria.

Conclusion

Implementation of the updated FDA’s monitoring criteria in the United Kingdom would significantly reduce clozapine discontinuation due to hematological reasons. The evidence suggests an urgent need for revising the UK clozapine monitoring guidelines to improve outcomes in treatment-resistant schizophrenia.
Transfer of lead from soil to pasture grass and milk near a metallurgical complex in the Peruvian Andes
Authors: Chirinos-Peinado Doris , Castro-Bedriñana Jorge , García-Olarte Edgar , Quispe-Ramos Rolando , Gordillo-Espinal Stephane
Published: January 2021

Milk quality is affected by the concentration of lead (Pb) in soil and pasture grasses used to raise cattle, especially in areas near mining-metallurgical complexes. In this study, the Pb content of soil and its transfer to grass and dairy milk in an area located to 20 km from the La Oroya Metallurgical Complex in Peru (altitude, >3,700 m s.a.l) was measured. Twenty soil samples (0–30 cm depth), 20 grass samples were collected, and 0.5 L of milk was obtained from 20 lactating cow in the communal cowshed. The Pb concentration (mg/kg) was quantified by flame atomic absorption spectrometry using a commercial Pb standard as quality control. The Pb average concentration in the soil, grass, and milk samples were 217.81 ± 39.48, 20.09 ± 2.83, and 0.58 ± 0.018 mg/kg (P < 0.01), respectively. The transfer factor (ratio of metal concentration) for Pb from soil to grass and from grass to milk was 0.095 and 0.031, respectively. The soil, grass, and milk samples all presented high Pb concentrations, with the milk samples containing 29-fold more Pb than the safety limit established by European regulations and were not suitable for human consumption or the manufacture of cheese, yogurt, and other derivatives. Our findings demonstrate that action to remediate these soils is critically needed.
Nephroprotective effect of gastrodin against lead-induced oxidative stress and inflammation in mice by the GSH, Trx, Nrf2 antioxidant system, and the HMGB1 pathway
Authors: Tian Zhi-Kai , Zhang Yu-Jia , Feng Zhao-Jun , Jiang Hong , Cheng Chao , Sun Jian-Mei , Liu Chan-Min
Published: January 2021

Gastrodin (GAS), the main phenolic glycoside derivative from Gastrodiaelata Blume, has several bio-activities. However, the molecular mechanisms of these protective actions currently remain unclear. This study aimed to investigate the mechanisms of GAS on lead (Pb)-induced oxidative stress and inflammation in the kidneys and primary kidney mesangial cells. Results indicated that GAS improved Pb-induced renal dysfunction and morphological changes in mice. GAS ameliorated Pb-induced inflammation in kidneys by reducing the TNF-α and IL-6 levels. GAS inhibited Pb-induced oxidative stress by regulating the glutathione, thioredoxin (Trx), and Nrf2 antioxidant systems. Furthermore, GAS supplementation increased the activation of SOD, GPx, HO-1, and NQO1 in the kidneys. GAS decreased the expression levels of HMGB1, TLR4, RAGE, MyD88, and NF-κB. These results were further confirmed in primary kidney mesangial cells. Collectively, this study demonstrated that GAS alleviated Pb-induced kidney oxidative stress and inflammation by regulating the antioxidant systems and the Nrf2 signaling pathway.

Highlights Gastrodin ameliorated Pb-induced kidney injury in mice. Gastrodin inhibited oxidative stress and inflammation in kidneys. Gastrodin activated the GSH, Trx and Nrf2 antioxidant system in kidneys. Gastrodin inhibited the activities of HMGB1. RAGE, TLR4, and MyD88
A comparative study of the effective response of di-potassium phosphate (K2HPO4) on physiological, biochemical and anatomical aspects of crops dwelling with zinc oxide nanoparticles toxicity
Authors: Yadav Vaishali , Arif Namira , Chauhan Devendra Kumar
Published: January 2021

The dipotassium phosphate (K2HPO4) is a source of phosphorus (P), which is an essential micronutrient for plant growth and reproduction and also acts as a stress alleviator against abiotic stresses. Therefore, it could also become a potential mineral to cope up with zinc oxide nanoparticles’ (ZnONPs) toxicity in crops. This study primarily includes synthesis, characterization and differential toxic impacts of ZnONPs on two crop plantsThis study includes synthesis, characterization and differential toxic impacts of ZnONPs on two crop plants, i.e. Triticum aestivum and Solanum lycopersicum, as well as assuage the toxic impacts of ZnONPs through nutrient management approach implied via supplementation of P. The growth and physiological changes under toxic doses of ZnONPs and ameliorative potential of P in crop plants were examined by analysing growth, intracellular Zn accumulation, photosynthetic pigment contents, the kinetics of photosystem II (PS II) photochemistry, root cell anatomy and cell viability via histochemical staining 4′,6-diamidino-2-phenylindole and propidium iodide. ZnONPs at 500 and 1000 μM concentrations significantly affected the growth, photosynthetic pigment and PS II photochemistry and cell death in both the plants. It also caused deformation in root anatomy of T. aestivum and S. lycopersicum. Whereas supplementation of P caused significant improvement against ZnONPs stress by causing remarkable enhancement in growth, photosynthetic pigments and activity of PS II photochemistry and decreased cell death. Moreover, the study also discloses the tolerant nature of S. lycopersicum comparing with T. aestivum seedlings. Thus, P is comparatively more effective in managing the ZnONPs toxicity in S. lycopersicum than in T. aestivum.
Modelling the impact of COVID-19-related programme interruptions on visceral leishmaniasis in India
Authors: Le Rutte Epke A , Coffeng Luc E , Muñoz Johanna , de Vlas Sake J
Published: January 2021

Background

In March 2020, India declared a nationwide lockdown to control the spread of coronavirus disease 2019. As a result, control efforts against visceral leishmaniasis (VL) were interrupted.

Methods

Using an established age-structured deterministic VL transmission model, we predicted the impact of a 6- to 24-month programme interruption on the timeline towards achieving the VL elimination target as well as on the increase of VL cases. We also explored the potential impact of a mitigation strategy after the interruption.

Results

Delays towards the elimination target are estimated to range between 0 and 9 y. Highly endemic settings where control efforts have been ongoing for 5–8 y are most affected by an interruption, for which we identified a mitigation strategy to be most relevant. However, more importantly, all settings can expect an increase in the number of VL cases. This increase is substantial even for settings with a limited expected delay in achieving the elimination target.

Conclusions

Besides implementing mitigation strategies, it is of great importance to try and keep the duration of the interruption as short as possible to prevent new individuals from becoming infected with VL and continue the efforts towards VL elimination as a public health problem in India.
Efficacy of Diving Reflex in Near-Term Fetal Tachycardia
Authors: Papa Marco , Mauri Lucia , Sandrini Camilla , Persico Nicola , Colli Anna Maria
Published: January 2021

BACKGROUND:

Sustained fetal supraventricular tachycardia is a potentially life-threatening disorder and is usually treated by administering antiarrhythmia drugs to the mother, which can require at least 48–72 hours to achieve normal sinus rhythm. In neonates with supraventricular tachycardia, first-line treatment is stimulation of the vagus nerve to elicit the diving reflex, commonly by application of a cold pack to the face, with a high, albeit sometimes temporary, success rate.

CASE:

We describe a case of fetal supraventricular tachycardia at term treated successfully by eliciting the diving reflex with an ice pack to the maternal abdomen over the lower uterine segment. The neonate was given propranolol augmented with flecainide because of recurrent supraventricular tachycardia. He remained in a stable sinus rhythm without side effects 5 months later.

CONCLUSIONS:

Cardioversion of fetal supraventricular tachycardia at term by eliciting the diving reflex could be offered to allow normal labor and vaginal delivery.
Obstetric Physicians' Beliefs and Knowledge on Guidelines and Screening Tools to Reduce Opioid Use After Childbirth
Authors: Downs Danielle Symons , Pauley Abigail M. , Leonard Krista S. , Satti Mohamed , Cumbo Nicole , Teti Isabella , Stephens Mark , Corr Tammy , Roeser Robert , Deimling Timothy , Legro Richard S. , Pauli Jaimey M. , Mackeen A. Dhanya , Bailey-Davis Lisa
Published: January 2021

OBJECTIVE:

To examine obstetric physicians' beliefs about using professional or regulatory guidelines, opioid risk-screening tools, and preferences for recommending nonanalgesic therapies for postpartum pain management.

METHODS:

A qualitative study design was used to conduct semi-structured interviews with obstetric and maternal–fetal medicine physicians (N=38) from two large academic health care institutions in central Pennsylvania. An interview guide was used to direct the discussion about each physicians' beliefs in response to questions about pain management after childbirth.

RESULTS:

Three trends in the data emerged from physicians' responses: 1) 71% of physicians relied on their clinical insight rather than professional or regulatory guidelines to inform decisions about pain management after childbirth; 2) although many reported that a standard opioid patient screening tool would be useful to inform clinical decisions about pain management, nearly all (92%) physician respondents reported not currently using one; and 3) 63% thought that nonpharmacologic pain management therapies should be used whenever possible to manage pain after childbirth. Key physician barriers (eg, lack time and evidence, being unaware of how to implement) and patient barriers (eg, take away from other responsibilities, no time or patience) to implementation were also identified.

CONCLUSION:

These findings suggest that obstetric physicians' individual beliefs and clinical insight play a key role in pain management decisions for women after childbirth. Practical and scalable strategies are needed to: 1) encourage obstetric physicians to use professional or regulatory guidelines and standard opioid risk-screening tools to inform clinical decisions about pain management after childbirth, and 2) educate physicians and patients about nonopioid and nonpharmacologic pain management options to reduce exposure to prescription opioids after childbirth.
Gestational Trophoblastic Disease
Authors: Soper John T.
Published: January 2021

This review summarizes the current evaluation and management of gestational trophoblastic disease, including evacuation of hydatidiform moles, surveillance after evacuation of hydatidiform mole and the diagnosis and management of gestational trophoblastic neoplasia. Most women with gestational trophoblastic disease can be successfully managed with preservation of reproductive function. It is important to manage molar pregnancies properly to minimize acute complications and to identify gestational trophoblastic neoplasia promptly. Current International Federation of Gynecology and Obstetrics guidelines for making the diagnosis and staging of gestational trophoblastic neoplasia allow uniformity for reporting results of treatment. It is important to individualize treatment based on their risk factors, using less toxic therapy for patients with low-risk disease and aggressive multiagent therapy for patients with high-risk disease. Patients with gestational trophoblastic neoplasia should be managed in consultation with an individual experienced in the complex, multimodality treatment of these patients.
Long-term Clinical Outcome of Major Adverse Vascular Events After Hypertensive Disorders of Pregnancy
Authors: Wu Mei-Yi , Hu Ping-Jen , Wong Chung-Shun , Chen Tzu-Ting , Hsueh Jui-Yuan , Lin Yuh-Feng , Tu Yu-Kang
Published: January 2021

OBJECTIVE:

To assess the association between hypertensive disorders of pregnancy and adverse events after pregnancy, including chronic kidney disease and major adverse cardiovascular events (cerebrovascular accident, coronary artery disease, or death).

METHODS:

A nationwide, population-based cohort study was conducted analyzing women with hypertensive disorders of pregnancy identified from Taiwan National Health Insurance Research Database from 2004 to 2015. Hypertensive disorders of pregnancy were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The study cohort was comprised of women aged 20–40 years diagnosed with hypertensive disorders of pregnancy from 2006 to 2013. The comparison group comprised of four randomly selected women without hypertensive disorders of pregnancy, matched for age and index date for each woman with hypertensive disorders of pregnancy. All the women were followed from the date of cohort entry until they developed chronic kidney disease or major adverse cardiovascular events or until the end of 2015, whichever occurred first. A Cox proportional hazard model was used to estimate the risk of chronic kidney disease and major adverse cardiovascular events.

RESULTS:

We identified 29,852 women with a diagnosis of hypertensive disorders of pregnancy and 119,408 matched women without hypertensive disorders of pregnancy who fit the inclusion criteria. The crude hazard ratios (HRs) were 5.22 (95% CI 4.67–5.83) and 2.26 (95% CI 1.99–2.57) for chronic kidney disease and major adverse cardiovascular events. After adjusting for potential confounders, hypertensive disorders of pregnancy was associated with a higher risk of chronic kidney disease (adjusted HR, 4.26; 95% CI 3.80–4.78), and major adverse cardiovascular events (adjusted HR, 2.15; 95% CI 1.89–2.45).

CONCLUSION:

This population-based cohort study indicated that women with hypertensive disorders of pregnancy are at a higher risk of chronic kidney disease and major adverse cardiovascular events than women without hypertensive disorders of pregnancy. Further studies are required to clarify the nature of these associations and to improve public health interventions.
Is There a Benefit to Weaning Pavlik Harness Treatment in Infantile DDH?
Authors: Bram Joshua T. , Gohel Shivani , Castañeda Pablo G. , Sankar Wudbhav N.
Published: January 2021

Background:

Following successful treatment of developmental hip dysplasia with a Pavlik harness, controversy exists over the benefit of continued harness use for an additional “weaning” period beyond ultrasonographic normalization versus simply terminating treatment. Although practitioners are often dogmatic in their beliefs, there is little literature to support the superiority of 1 protocol over the other. The purpose of this study was to compare the radiographic outcomes of 2 cohorts of infants with developmental hip dysplasia treated with Pavlik harness, 1 with a weaning protocol and 1 without.

Methods:

This was a comparative review of patients with dislocated/reducible hips and stable dysplasia from 2 centers. All patients had pretreatment ultrasounds, and all started harness treatment before 3 months of age. On the basis of power analysis, a sufficient cohort of hips were matched based on clinical examination, age at initiation, initial α angle, and initial percent femoral head coverage. Patients from institution W (weaned) were weaned following ultrasonographic normalization, whereas those from institution NW (not weaned) immediately ceased treatment. The primary outcome was the acetabular index at 1 year of age.

Results:

In total, 16 dislocated/reducible and 16 stable dysplastic hips were matched at each center (64 total hips in 53 patients). Initial α angle and initial femoral head coverage were not different between cohorts for either stable dysplasia (P=0.59, 0.81) or dislocated/reducible hips (P=0.67, 0.70), respectively. As expected, weaned hips were treated for significantly longer in both the stable dysplasia (1540.4 vs. 1066.3 h, P<0.01), and dislocated/reducible cohorts (1596.6 vs. 1362.5 h, P=0.01). Despite this, we found no significant difference in the acetabular index at 1 year in either cohort (22.8 vs. 23.1 degrees, P=0.84 for stable dysplasia; 23.9 vs. 24.8 degrees, P=0.32 for Ortolani positive).

Conclusions:

Despite greater total harness time, infants treated with additional Pavlik weaning did not demonstrate significantly different radiographic results at 1 year of age compared with those who were not weaned. However, differences in follow-up protocols between centers support the need for a more rigorous randomized controlled trial.

Level of Evidence:

Level III.
Nosocomial Infection
Authors: Kollef Marin H. , Torres Antoni , Shorr Andrew F. , Martin-Loeches Ignacio , Micek Scott T.
Published: January 2021

Objective:

The first 70 years of critical care can be considered a period of “industrial revolution-like” advancement in terms of progressing the understanding and care of critical illness. Unfortunately, like the industrial revolution’s impact on the environment, advancing ICU care of increasingly elderly, immunosuppressed, and debilitated individuals has resulted in a greater overall burden and complexity of nosocomial infections within modern ICUs. Given the rapid evolution of nosocomial infections, the authors provide an updated review.

Data Sources and Study Selection:

We searched PubMed and OVID for peer-reviewed literature dealing with nosocomial infections in the critically ill, as well as the websites of government agencies involved with the reporting and prevention of nosocomial infections. Search terms included nosocomial infection, antibiotic resistance, microbiome, antibiotics, and intensive care.

Data Extraction and Data Synthesis:

Nosocomial infections in the ICU setting are evolving in multiple domains including etiologic pathogens plus novel or emerging pathogens, prevalence, host risk factors, antimicrobial resistance, interactions of the host microbiome with nosocomial infection occurrence, and understanding of pathogenesis and prevention strategies. Increasing virulence and antimicrobial resistance of nosocomial infections mandate increasing efforts toward their prevention.

Conclusions:

Nosocomial infections are an important determinant of outcome for patients in the ICU setting. Systematic research aimed at improving the prevention and treatment of nosocomial infections is still needed.
Flap Neurotization in Breast Reconstruction with Nerve Allografts: 1-year Clinical Outcomes
Authors: Momeni Arash , Meyer Shannon , Shefren Kerry , Januszyk Michael
Published: January 2021

Background:

Autologous breast reconstruction is widely regarded as the gold standard approach following mastectomy. However, the lack of sensation continues to present a reconstructive challenge. In this study, clinical outcomes following abdominal flap neurotization with processed human nerve allograft were investigated.

Methods:

In this prospective analysis, patients who underwent microsurgical breast reconstruction with (Group 1) or without (Group 2) abdominal flap neurotization at a single institution were investigated. Processed human nerve allograft (Avance, AxoGen, Alachua, Fla.) was used in all cases of flap neurotization. Only patients with a follow-up of ≥12 months were included. Cutaneous pressure threshold was tested using Semmes-Weinstein monofilaments (SWMF) at 9 pre-defined locations.

Results:

A total of 59 patients (96 breasts) were enrolled into the registry. Of these, 22 patients (Group 1: N = 15, 22 breasts; Group 2: N = 7, 14 breasts) had a complete data set with ≥12 months follow-up. Measuring cutaneous pressure thresholds, we observed a greater likelihood for return of protective sensation (SWMF ≤ 4.31) in neurotized breasts in 8 of the 9 examined zones. Additionally, flap neurotization was associated with a greater likelihood for return of protective sensation in the majority of the reconstructed breast—that is, ≥5 zones (55% versus 7%; P < 0.01).

Conclusion:

Flap neurotization using processed nerve allograft resulted in a greater degree of return of protective sensation to the reconstructed breast than reconstructions without neurotization at ≥12 months.
Extranodal Natural Killer/T-cell Lymphoma, Nasal Type: Diagnosis and Treatment
Authors: van Doesum Jaap A. , Niezink Anne G. H. , Huls Gerwin A. , Beijert Max , Diepstra Arjan , van Meerten Tom
Published: January 2021

The aggressive lymphoma, extranodal natural killer/T-cell lymphoma-nasal type, is strongly associated with Epstein-Barr virus (EBV) and is most common in Asia and in South and Central America. By contrast, incidence is low in the United States and Europe, where extranodal natural killer/T-cell lymphoma represents only 0.2%-0.4% of all newly diagnosed non-Hodgkin lymphomas. At diagnosis, it is important to test for EBV DNA in plasma by polymerase chain reaction and to carry out positron emission tomography/computer tomography and magnetic resonance imaging of the nasopharynx. In stage I/II disease, radiotherapy is the most important treatment modality, but in high-risk stage I/II disease (stage II, age > 60 y, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group performance score ≥2, primary tumor invasion), it should be combined with chemotherapy. The most optimal responses are reached with nonmultidrug resistance-based therapy (eg, asparaginase- or platinum-based therapy). Therapeutic approaches consist of either platinum-based concurrent chemoradiotherapy or sequential chemoradiotherapy. The minimum dose of radiotherapy should be 50-56 Gy. Treatment of stage III/IV disease consists of 3 cycles of chemotherapy followed by autologous hematopoietic cell transplantation. Allogeneic hematopoietic cell transplantation should only be considered in case of relapsed disease or after difficulty reaching complete remission. During treatment and follow-up, plasma EBV levels should be monitored as a marker of tumor load.
Comparing the ICD-11 chronic pain classification with ICD-10: how can the new coding system make chronic pain visible? A study in a tertiary care pain clinic setting
Authors: Zinboonyahgoon Nantthasorn , Luansritisakul Choopong , Eiamtanasate Sarasate , Duangburong Sirikan , Sanansilp Virachat , Korwisi Beatrice , Barke Antonia , Rief Winfried , Treede Rolf-Detlef
Published: January 2021

Pain is a frequent reason for patients to ask for medical services. However, systematic information about the extent and impact of pain, especially in developing countries, has not been available up to now. We evaluated whether the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD) can fill this gap by coding all electronic out-patient medical records of the pain clinic at Siriraj Hospital in Thailand in 2019 (8714 visits), using the ICD-10 and ICD-11 browsers referenced on the WHO websites. The 3 most frequent pain-related codes in ICD-10 were R52.2 “other chronic pain” (29%), M54.5 “low back pain” (18%), and M79.6 “pain in limb” (13%). In ICD-11, the 3 most frequent codes were MG30.31 “chronic secondary musculoskeletal pain associated with structural changes” (28%), MG30.51 “chronic peripheral neuropathic pain” (26%), and MG30.10 “chronic cancer pain” (23%). Thus, using the currently valid ICD-10 system, roughly one-third of patient encounters were coded as “other chronic pain,” and the next 2 were specifying the pain region rather than any underlying cause. By contrast, ICD-11 coding of the same patients identified underlying causes (bones and joints, somatosensory nervous system, cancer, or surgery), which provide guidance towards differential patient management. In our pain clinic, most patients suffered from chronic cancer pain, chronic neuropathic pain, and chronic secondary musculoskeletal pain, which were poorly defined or nonexistent in the current ICD-10 coding system. Compared with the ICD-10, the ICD-11 provides more detailed diagnostic categories and is more informative for clinical use, research, and resource allocation for pain-related conditions.
Facial Paralysis From Post-transplant Lymphoproliferative Disorder
Authors: Toivonen Joonas , Shulman David S. , Shusterman Suzanne , Robson Caroline D. , Saillant Meredith , Poe Dennis
Published: January 2021

Objective:

We report a case of facial paresis and profound hearing loss from post-transplant lymphoproliferative disorder (PTLD) in a pediatric patient with neuroblastoma.

Patient:

Three-year-old boy with rapidly progressive right facial paresis and sensorineural hearing loss. High-risk neuroblastoma had been diagnosed 1 year earlier, treated with chemotherapy and resection of the adrenal primary tumor. Two months after two autologous hematopoietic stem cell transplantations (HSCT), the patient developed facial paralysis. Magnetic resonance imaging (MRI) showed bilateral progressive internal auditory canal (IAC) enhancing lesions with a mass lesion on the right and wispy enhancement on the left and enhancement within the right cochlea. Lumbar puncture (LP) was positive for Epstein-Barr virus (EBV) making the diagnosis of PTLD most probable. Biopsy of the right IAC lesion was deferred because of potential procedural risks including intradural spread of tumor or fungus. The patient was treated with anti-fungal therapy and systemic rituximab without improvement. Subsequent intrathecal rituximab resulted in improvement of lesions on MRI and clearance of EBV from the cerebrospinal fluid (CSF).

Interventions:

Mastoidectomy for biopsies from the mastoid and middle ear. Intrathecal treatment with rituximab.

Main Outcome Measures:

Imaging assessment of IAC lesion, CSF EBV titers, facial nerve function.

Results:

Gradual resolution of IAC mass lesions, remission of PTLD, and facial improvement from House–Brackmann score of 4 to 3.

Conclusions:

PTLD causing facial paresis after autologous HSCT has not been previously reported and may be considered in the differential diagnosis of lesions causing facial paresis in patients who have received a stem cell or solid organ transplant.
Comparison of different activators of coagulation by turbidity analysis of hereditary dysfibrinogenemia and controls
Authors: Marchi Rita , Neerman-Arbez Marguerite , Gay Valérie , Mourey Guillaume , Fiore Mathieu , Mouton Christine , Gautier Philippe , De Moerloose Philippe , Casini Alessandro
Published: January 2021

Turbidity analysis is widely used as a quantitative technique in hereditary dysfibrinogenemia. We aimed to compare several coagulation triggers in hereditary dysfibrinogenemia and control plasmas. We included 20 patients with hereditary dysfibrinogenemia, 19 with hotspot mutations Aα Arg35His (n = 9), Aα Arg35Cys (n = 2), γ Arg301His (n = 6), γ Arg301Cys (n = 2), and one with Aα Phe27Tyr, and a commercial pooled normal plasma. Fibrin polymerization was activated by bovine or human thrombin or tissue factor (TF), in the presence or absence of tissue type plasminogen activator. The lag time (min), slope (mOD/s), maximum absorbance (MaxAbs, mOD), and area under the curve (AUCp, OD s) were calculated from the fibrin polymerization curves and the time for 50% clot degradation (T50, min), AUCf (OD s) and the overall fibrinolytic potential from fibrinolysis curves. The lag time was significantly shorter and AUC increased in Aα Arg35His patients with bovine thrombin as compared with human thrombin. The MaxAbs and AUCp were significantly higher in γArg301His patients with bovine thrombin compared with human thrombin. Fibrin polymerization parameters of patients’ samples were closer to those of control when assessed with TF compared with both human and bovine thrombin. T50 and overall fibrinolytic potential were similar in all samples regardless of the coagulation trigger used, however, with TF the AUCf of Aα Arg35His and γ Arg301His groups were significantly decreased compared with control. Bovine and human thrombin cannot be used equally for studying fibrin polymerization in hotspot hereditary dysfibrinogenemia or control plasmas.
Tranexamic acid versus aminocapróic acid in multiple doses via the oral route for the reduction of postoperative bleeding in total primary hip arthroplasty: a prospective, randomized, double-blind, controlled study
Authors: Morales-Avalos Rodolfo , Ramos-Morales Tomas , García-Pedro Jesús A. , Espinoza-Galindo Ana M. , Acosta-Olivo Carlos , Morcos-Sandino Michelle , Silva-Ramos Héctor N.G. , Peña-Martínez Víctor M. , Rodríguez-Torres Raymundo A. , Vilchez-Cavazos Félix
Published: January 2021

To compare the effects of oral ε-aminocaproic acid (EACA) as a hemostatic agent versus the use of oral tranexamic acid (TXA) administered in multiple doses pre and postsurgery in patients undergoing elective primary total hip arthroplasty (THA). We enrolled 102 patients that were randomly divided into two groups: received three oral doses of EACA (2000 mg per dose) or three oral doses of TXA (1300 mg per dose). The medication was given according to the following schedule: 2 h before surgery and 6 and 12 h after surgery. The variables analyzed to compare the effectiveness of the hemostatic agents were total blood loss, hidden blood loss, external blood loss, transfusion rate, intraoperative blood loss, decreases in hemoglobin and hematocrit values, surgical drainage output, visual analog scale, and surgical complications. There were no significant differences between any of the study variables for the group receiving oral TXA and the group receiving oral EACA (P > 0.05). Our study showed that the use of oral EACA was similar to its counterpart TXA regarding the evaluated parameters. TXA did not have superior blood conservation effects, safety profile, or differences in functional scales compared with EACA in THA. We consider the use of multiple oral doses of aminocaproic acid at the selected dose to be effective as a standard protocol to achieve less blood loss and a lower rate of transfusion and adverse events related to the medication in patients undergoing a THA.
Tranexamic acid rapidly inhibits fibrinolysis, yet transiently enhances plasmin generation in vivo
Authors: Draxler Dominik F. , Zahra Saffanah , Goncalves Isaac , Tran Huyen , Hanafi Gryselda , Ho Heidi , Keragala Charithani B. , Ilich Anton , Key Nigel S. , Myles Paul S. , Medcalf Robert L.
Published: January 2021

Tranexamic acid (TXA) is a lysine analogue that inhibits plasmin generation and has been used for decades as an antifibrinolytic agent to reduce bleeding. Recent reports have indicated that TXA can paradoxically promote plasmin generation. Blood was obtained from 41 cardiac surgical patients randomly assigned to TXA or placebo before start of surgery (preOP), at the end of surgery (EOS), then again on postoperative day 1 (POD-1) as well as POD-3. Plasma levels of tissue-type plasminogen activator (t-PA), urokinase (u-PA), the plasmin-antiplasmin (PAP) complex, as well as t-PA and u-PA-induced clot lysis assays were then determined. Clot lysis and PAP complex levels were also assessed in healthy volunteers before and at various time points after taking 1 g TXA orally. Surgery induced an increase in circulating t-PA, yet not u-PA at EOS. t-PA levels were unaffected by TXA; however, u-PA levels were significantly reduced in patients on POD-3. t-PA and u-PA-induced clot lysis were both inhibited in plasma from TXA-treated patients. In contrast, PAP complex formation, representing plasmin generation, was unexpectedly enhanced in the plasma of patients administered TXA at the EOS time point. In healthy volunteers, oral TXA effectively blocked fibrinolysis within 30 min and blockade was sustained for 8 h. However, TXA also increased PAP levels in volunteers 4 h after administration. Our findings demonstrate that TXA can actually augment PAP complex formation, consistent with an increase in plasmin generation in vivo despite the fact that it blocks fibrinolysis within 30 min. This may have unanticipated consequences in vivo.
A novel mutation (Leu60Pro) in a Chinese pedigree with hereditary factor XI deficiency
Authors: Xie Haixiao , Liu Meina , Zou Anqing , Xie Yaosheng , Ye Jiajia
Published: January 2021

To analyse F11 gene mutations in a Chinese pedigree with hereditary factor XI (FXI) deficiency and investigate the molecular mechanism. The plasma FXI activity and FXI antigen of the proband and the family members were detected by clotting assay and ELISA, respectively. The F11 gene was amplified by PCR and sequenced directly. Online bioinformatics software were needed to analyse the mutations. The proband showed a prolonged activated partial thromboplastin time (93.3 s), whose FXI activity and FXI antigen were low to 2, 4.5%, respectively. A novel mutation c.233T>C (p.Leu60Pro) in exon 4 and a previously described mutation c.1253G>T (Gly400Val) were found in the proband. Protein Leu60 is conserved highly among homologous species. Bioinformatics software indicated that Leu60Pro mutation might affect the protein function. Other coagulation abnormalities were not found. We preliminarily considered the mutations Leu60Pro and Gly400Val were responsible for the decrease FXI level in the family. Leu60Pro mutation in the F11 gene has not been described elsewhere.