bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectopic thyroid in the gallbladder accompanied with gallbladder adenoma
Authors: Li Yanxu , Li Shijun , Wang Meng , Tong Ling
Published: December 2019

Rationale:

Ectopic thyroid is most common in the tongue. Here we reported a rare case of thyroid tissue located in the gallbladder wall, accompanied with adenoma and a cyst lined with pseudostratified ciliated columnar epithelium in the neck region of gallbladder neck.

Patient concerns:

A 39-year-old female presented with recurrent upper abdominal pain and radiating back pain.

Diagnoses:

Based on ultrasonography, gallbladder polyps and calculous cholecystitis were suspected.

Interventions:

The patient was treated by laparoscopic cholecystectomy, and thyroid tissue located in the gallbladder wall was found. Histopathological examination showed no features of papillary thyroid neoplasm.

Outcomes:

The patient had no thyroid nodules or suspicious enlarged lymph nodes, and no other symptoms or complications by follow-up for 2.5 years up to September 2019.

Lessons:

We should pay attention to the rare location of ectopic thyroid tissue in the gallbladder and rule out primary thyroid malignancy to avoid unnecessary overtreatment.
Serum proteome profiles to differentiate Crohn disease from intestinal tuberculosis and primary intestinal lymphoma
Authors: Ning Longgui , Shan Guodong , Sun Zeyu , Lou Xinhe , Zhang Fenming , Li Sha , Du Haojie , Yu Jinghua , Chen Hongtan , Xu Guoqiang
Published: December 2019

The differential diagnosis of Crohn disease (CD) from intestinal tuberculosis (ITB) and primary intestinal lymphoma (PIL) is challenging in patients who exhibit atypical clinical characteristics. The aim of the present study was to explore the serum proteome profiles of CD, PIL and ITB and to identify their differentiations.

Treatment-naïve patients with CD (n = 10), PIL (n = 10) and ITB (n = 10) were enrolled in the present study. Differentially expressed proteins (DEPs) in patient serum samples were compared between groups using tandem mass tag labeled proteomic technology. A principal component analysis (PCA) plot and volcano maps were also visualized. Functional pathway analysis was performed using Reactome. The Area under the Curve (AUC) was calculated for each DEP.

A total of 818 proteins were identified through proteomic quantification. Among them, 108 DEPs were identified to be differentiated between CD and ITB, 105 proteins between CD and PIL and 55 proteins between ITB and PIL. The proteome from the three groups was distinguishable in the PCA plot. The results revealed that 19, 12, and 10 proteins (AUC ≥ 0.95) were differentially expressed between CD and PIL, CD and ITB, and PIL and ITB, respectively. Among these DEPs, tumor necrosis factor ligand superfamily member 13 was higher in CD than in ITB and PIL. Peroxiredoxin-5, T-complex protein 1 subunit Gamma, CutA, and Fibulin-5 were increased in CD and PIL when compared with ITB. The levels of fibrinogen chains were also significantly higher in patients with PIL compared with CD.

The current study demonstrated that serum proteome was distinguishable among patients with CD, PIL, and ITB. The identified proteins may assist in the clinical differentiation among them.
Complications of therapeutic plasma exchange
Authors: Lu Jing , Zhang Lijuan , Xia Cheng , Tao Yuhong
Published: December 2019

Therapeutic plasma exchange (TPE) is now widely used in therapy of multiple diseases in children, by removing the plasma with pathogenic agents from patients. However, adverse reactions may limit its application.

A retrospective cohort study of 435 hospitalized children treated with 1201 plasma exchange procedures between January 2013 and July 2018 were enrolled.

Complications occurred in 152 procedures (12.7%); 90 procedures (7.5%) had ≥2 complications. No death occurred. The most common complications were pruritus and urticaria (7%), followed by hypertension (1.92%) and hypotension (1.17%). One child had an outbreak of disseminated cryptococcosis neoformans infection, another child developed anaphylactic shock, and 3 children presented toxic epidermal necrolysis after TPE. The incidence of pruritus and urticaria was higher in children of the 6∼15 year group (P < .05) compared with other age groups. There was no significant difference in the incidence of hypertension and hypotension in children at different ages and weights (P > .05). Compared with other diseases, anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis led to a higher incidence of complications in children (P < .05).

The results suggest that TPE is a relatively safe procedure for children, and most of the complications are mild. The most common complication is pruritus and urticaria. However, serious complications such as toxic epidermal necrolysis and infection should still be taken seriously.
Novel biomarkers for potential risk stratification of drug induced liver injury (DILI)
Authors: Danjuma Mohammed Ibn-Mas’ud , Sajid Jamal , Fatima Haajra , Elzouki Abdel-Naser
Published: December 2019

Background:

Drug induced liver injury (DILI) is an increasing cause of acute liver injury especially with increasing need for pharmacotherapy of widening comorbidities amongst our ever-aging population. Uncertainty however remains regarding both acceptable and widely agreeable diagnostic algorithms as well a clear understanding of mechanistic insights that most accurately underpins it. In this review, we have explored the potential role of emerging novel markers of DILI and how they could possibly be integrated into clinical care of patients.

Methods:

We explored PUBMED and all other relevant databases for scientific studies that explored potential utility of novel biomarkers of DILI, and subsequently carried out a narrative synthesis of this data. As this is a narrative review with no recourse to patient identifiable information, no ethics committee's approval was sought or required.

Results:

Novel biomarkers such as microRNA-122 (miR-122) profiles, high mobility group box-1 (HMGB1), glutamate dehydrogenase (GLDH), and cytokeratin-18 (K-18), amongst others do have the potential for reducing diagnostic uncertainties associated with DILI.

Conclusion:

With the increasing validation of some of the novel liver biomarkers such as K-18, mir-122, HMGB-1, and GLDH, there is the potential for improvement in the diagnostic uncertainty commonly associated with cases of DILI.
Herb medicine for relieving radiation induced oral mucositis
Authors: Wang Gui , Jia Liqun
Published: December 2019

Background:

Oral mucositis (OM) is a common and unavoidable side effect in patients suffering from head and neck cancer who are undergoing radiotherapy. It is characterized by unbearable pain, as well as eating and speech disorders. This has serious negative effects on the patients’ quality of life and can even reduce radiotherapy tolerance, ultimately resulting in a poor prognosis. At present, many prevention and treatment methods are still in the experimental stage, and the efficacies are controversial.

Methods:

Four English databases: Medline via pubmed, EMBASE, the Cochrane Library, Web of Science and another 4 Chinese databases: China National Knowledge Infrastructure (CNKI), China Science and Technology Journal database (VIP), Wanfang Database and CBM, will be searched from inception to August 2019. All randomized controlled trials in Chinese and English language will be included. Literature selection, data extraction and quality assessment will be completed by 2 independent authors. The primary outcomes will include the incidence of OM (1–4 grade) and the pain degree. The onset time of OM, the improvement rate for quality of life, and any adverse effects will be evaluated as the secondary outcomes. The data will be synthesized by Review Manager and Stata software.

Results:

This study provides a high-quality synthesis from existing evidence for Chinese herbal medicine in radiotherapy induced OM treatment, according to the criteria: incidence of OM, onset time of OM, status changes in quality of life and adverse events.

Conclusion:

This study will provide evidence to help determine whether Chinese herbal medicine is effective and safe for use in the prevention and/or treatment of radiotherapy induced OM.

Ethics and dissemination:

No additional formal ethical recognition or informed consent is required since no primary data collection is involved. The study result will be published in peer-reviewed journals or at related conferences.

PROSPERO registration number: PROSPERO CRD42019141900.
Patient safety management systems, activities and work environments related to hospital-level patient safety culture
Authors: Fujita Shigeru , Wu Yinghui , Iida Shuhei , Nagai Yoji , Shimamori Yoshiko , Hasegawa Tomonori
Published: December 2019

Improvement in patient safety culture requires constant attention. This study aimed to identify hospital-level elements related to patient safety culture, such as patient safety management systems, activities and work environments.

Two questionnaire surveys were administered to hospitals in Japan in 2015 and 2016. The first survey aimed to determine which hospitals would allow their staff to respond to a questionnaire survey. The second survey aimed to measure the patient safety culture in those hospitals. Patient safety culture was assessed using the Hospital Survey on Patient Safety Culture (HSOPS). The relationship of hospital-level patient safety culture with the aforementioned elements in each hospital was analyzed.

The response rate to the first survey was 22% (721/3270), and 40 eligible hospitals were selected from the respondents. The second survey was administered to healthcare workers in those 40 hospitals, and the response rate was 94% (3768/4000). The proportion of respondents who had 7 or more days off each month was related to the scores of 7 composites and the Patient Safety Grade of HSOPS. Both the presence of a mission statement describing patient safety and the proportion of respondents who participated in in-house patient safety workshops at least twice annually were related to the scores of 5 composites and the Patient Safety Grade of HSOPS.

Our study suggests that the number of days off each month, the presence of a hospital patient safety mission statement, and the participation rate in in-house patient safety workshops might be key factors in creating a good patient safety culture within each hospital.
Comparison of adductor canal block with periarticular infiltration analgesia in total knee arthroplasty
Authors: Zhang Lu-Kai , Li Qiang , Zhu Fang-Bing , Liu Jun-Sheng , Zhang Zhi-Jin , Zhang Yu-Hang , Quan Ren-Fu
Published: December 2019

Background:

Total knee arthroplasty (TKA) is accompanied by moderate to severe postoperative pain. Multimodal analgesia, such as femoral nerve block, periarticular infiltration analgesia (PIA), and patient-controlled intravenous analgesia, have been used for postoperative analgesia. Recently, randomized controlled trials have compared the efficacy of the adductor canal block (ACB) and the PIA in patients undergoing TKA. However, there is no definite answer as to the efficacy and safety of the ACB compared with the PIA.

Method:

Randomized controlled trials about relevant studies were searched from PubMed (1996 to May 2019), Embase (1980 to May 2019), and Cochrane Library (CENTRAL, May 2019). Five studies which compared the ACB with the PIA methods were included in our meta-analysis.

Results:

Five studies containing 413 patients met the inclusion criteria. There were no significant differences between the ACB and the PIA group in visual analog scale (VAS) score at rest (P = .14) and movement (P = .18), quadriceps muscle strength (P = .95), complications (P = .78), length of stay (LOS) (P = .54), and time up and go (TUG) test (P = .09), While patients in the ACB group had less equivalent morphine consumption (P < .05) compared with the PIA group.

Conclusions:

Our pooled data indicated the ACB group reduced the equivalent morphine consumption compared with the PIA group, with no statistically significant differences in the VAS score, quadriceps muscle strength, TUG test, complications, and LOS.
Subsurface calcification of hydrophilic refractive multifocal intraocular lenses with a hydrophobic surface
Authors: Bang Seung Pil , Moon Kun , Lee Jong-Ho , Jun Jong Hwa , Joo Choun-Ki
Published: December 2019

Rationale:

Opacification of monofocal intraocular lenses (IOLs) of various designs and materials has been reported. Hydrophilic acrylic IOLs are more prone to opacification than hydrophobic IOLs, but IOL surface modification by hydrophobic materials may improve biocompatibility, and few opacifications of such monofocal lenses have been reported to date. However, here we describe the characteristics of opacification of hydrophilic refractive multifocal IOLs with a hydrophobic surface modification in a cluster of patients who underwent uneventful cataract surgery.

Patient Concerns:

In this retrospective observational case series, the medical records of 7 patients in whom opacification of the IOL was identified after implantation of LS-313 MF30 (Lentis M plus, Oculentis), from November 2017 to May 2019, were reviewed.

Diagnosis:

All patients had undergone bilateral implantation of LS-313 MF30 IOLs. Ten eyes of 7 patients showed significant opacification at a mean 49.1 ± 10.2 months postoperatively.

Interventions:

The IOLs of 4 cases were explanted.

Outcomes:

All of the opacified cases had received LS-313 MF30 IOLs from February 2014 to August 2014 and experienced decreased visual acuity after 44.6 ± 10.5 months. The explanted IOLs of 4 cases were evaluated by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Alizarin-red, and von Kossa staining. These explanted IOLs showed fine and evenly distributed, whitish deposits on the entire IOL, particularly below the surface. Although the constituent of the deposits was identified as calcium by Alizarin-red and von Kossa stain, SEM, and EDX analysis showed no surface deposits of calcium. Paraffin-embedded sections of the IOLs were prepared, and calcium deposition was confirmed by EDX analysis at the subsurface region of the IOL.

Lessens:

Significant opacification of these hydrophilic refractive multifocal IOLs with hydrophobic surface modification was found to be due to abnormal calcification of the subsurface of the IOL. Clinicians must be aware of the opacification of this IOL design, despite surface modification. In particular, it should be noted that there is a high likelihood that the patient may experience vision-related symptoms even with moderate opacity and that opacification may lead to a burdensome IOL exchange.
Synergistic association of FOXP3+ tumor infiltrating lymphocytes with CCL20 expressions with poor prognosis of primary breast cancer
Authors: Zhao Xia , Li Yanping , Wang Xiaoli , Wu Jiangping , Yuan Yanhua , Lv Shuzhen , Ren Jun
Published: December 2019

Studies have shown that forkhead/winged helix transcription factor P3 (FOXP3)+ tumor infiltrating lymphocytes (TILs) are intimately associated with invasion and survival of many invasive tumors. The inflammatory chemokine ligand 20 (CCL20) and its receptor CCR6 were found to be associated with tumor prognosis in some studies. Although increases in FOXP3+ TILs infiltration and CCL20 expression have been revealed in several malignancies, their correlation in human breast tumors is as yet unclear.

Surgically resected samples from 156 patients with invasive breast cancer (BC) were assessed for the expression of FOXP3 and CCL20 by immunohistochemistry. Correlation between their expressions and the association with clinicopathological characteristics and patient's prognosis were studied. Forty pairs of fresh BC and their nontumor adjacent tissues (NATs) in BC were carried out by real-time quantitative PCR (qRT-PCR) to evaluate the correlation between FOXP3 and CCL20 mRNA expression.

CCL20 and FOXP3+ TILs mRNA expression in tumor tissue demonstrated a high correlation (rs = 0.359, P < .001) in this cohort of breast cancer patients. Both elevated CCL20 expression and FOXP3+ TILs infiltration were significantly correlated with high histological grade, positive human epidermal growth factor receptor-2 (HER2), high Ki67 index, and axillary lymph node metastases. Tumors with concomitant high expressions of both markers had the worst prognosis. Multivariate analysis showed that these 2 markers were independent predictors of overall survival. The patients with axillary lymph node metastases with the concomitant CCL20 high expression and increased FOXP3+ TILs infiltration had the worst overall survival (OS) (P < .001), In lymph node-negative breast cancer patients, the status of CCL20 and FOXP3 was not related to OS (P 
= .22).

The results suggest that CCL20 and FOXP3+ TILs may have synergistic effects, and their upregulated expressions may lead to immune evasion in breast cancer. Combinatorial immunotherapeutic approaches aiming at blocking CCL20 and depleting FOXP3 might improve therapeutic efficacy in breast cancer patients.
Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer
Authors: Tantawy Azza A. , Ragab Iman A. , Ismail Eman A. , Ebeid Fatma S.E. , Al-Bshkar Ramadan M.
Published: December 2019

Background:

Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis.

Aim:

We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He.

Materials and Methods:

This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks’ treatment with oral ion and were followed up with complete blood count and iron profile.

Results:

Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found.

Conclusions:

We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.
Utility of Nuclear Grading System in Epithelioid Malignant Pleural Mesothelioma in Biopsy-heavy Setting
Authors: Zhang Yu Zhi , Brambilla Cecilia , Molyneaux Philip L. , Rice Alexandra , Robertus Jan L. , Jordan Simon , Lim Eric , Lang-Lazdunski Loic , Begum Sofina , Dusmet Michael , Anikin Vladimir , Beddow Emma , Finch Jonathan , Asadi Nizar , Popat Sanjay , Cookson William O.C. , Moffatt Miriam F. , Nicholson Andrew G.
Published: December 2019

Nuclear grading systems for epithelioid malignant pleural mesothelioma (MPM) have been proposed but it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies only. The median number of sites sampled was 1, with a median maximum tissue dimension of 17 mm (biopsy) and 150 mm (resection). The median overall survival (OS) was 14.7 months. The frequencies of grade I, II, and III tumors were 31% (132/563), 52% (292/563), and 17% (94/563). Grade I tumors were associated with the most favorable median OS (24.7 mo) followed by grades II (12.7 mo) and III (7.2 mo). The 2-tier nuclear grade separated tumors into low grade (19.3 mo) and high grade (8.9 mo). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear grade, and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant growth pattern, necrosis, and atypical mitosis (all P<0.001 except 2-tier nuclear grade, P=0.001). In the scenario of a single- site biopsy with tissue dimension ≤10 mm, none but age (P=0.002) were independently predictive. Our data also suggested sampling 3 sites or a maximum tissue dimension of at least 20 mm from a single site is optimal for nuclear grade assessment. In conclusion our study confirmed the utility of nuclear grade in epithelioid MPM using a biopsy-heavy cohort provided the tissue sample met minimum dimensional criteria.
Introducing a Virtual Fracture Clinic Increases Efficiency and Reduces Costs in Torus Fracture Management
Authors: Seewoonarain Sheena , Babu Satish , Sangoi Dhrumin , Avasthi Adhish , Ricketts David
Published: December 2019

Background:

Torus fractures of the distal radius are both a common pediatric forearm fracture and a common source of referral to orthopedic departments. Management of these injuries has moved away from traditional casting methods to using splints and softcasts.

Aim:

With the recent introduction of a virtual fracture clinic (VFC), we sought to improve our compliance with guidelines while ensuring all patients undergo review in the clinic.

Methods:

We audited the management of patients before and after the introduction of the VFC with new management protocols for torus fracture patients.

Results:

There was a 51% decrease in patients managed using plaster of Paris with 5% treated with a softcast and 59% using a splint.

Outcome:

Using the VFC can improve the management of patients with torus fractures and provide a cost-saving and a more positive experience for patients.
Strabismus in Unicoronal Craniosynostosis: Effect of Orbital Dysmorphology and Fronto-Orbital Advancement and Remodeling
Authors: Yu Jason W. , Xu Wen , Wink Jason D. , Wes Ari M. , Bartlett Scott P. , Taylor Jesse A.
Published: December 2019

Background:

The purpose of this study was to determine what craniometric changes occur to both orbits of unicoronal craniosynostosis patients undergoing fronto-orbital advancement and remodeling, and which of these changes are associated with new onset of postoperative strabismus.

Methods:

A retrospective analysis was performed of the preoperative and postoperative orbits of 24 unicoronal craniosynostosis patients and the orbits of 24 control subjects, totaling 144 orbits. Eight parameters were evaluated using multivariate logistic regression analysis. One of the parameters was modified orbital index, an indicator of severity of harlequin deformity.

Results:

Significant differences in orbital dimensions and angles were present bilaterally in unicoronal craniosynostosis orbits when compared to controls. Fronto-orbital advancement and remodeling increased the ipsilateral unicoronal craniosynostosis orbital volume from 13,184 ± 2003 mm3 to 16,220 ± 2323 mm3 (p < 0.001). Ipsilateral horizontal cone angles were increased from 48 ± 5 degrees to 54 ± 7 degrees (p = 0.004). Ipsilateral vertical cone angles were decreased from 73 ± 8 degrees to 66 ± 10 degrees (p = 0.003). Ipsilateral modified orbital index improved from 0.83 ± 0.06 to 0.88 ± 0.06 (p = 0.003). Three of the 19 unicoronal craniosynostosis patients developed transient postoperative strabismus. Logistic regression analysis displayed a strong significant association between new-onset strabismus and a change in modified orbital index with a coefficient of 30.84 ± 14.51 (p < 0.05).

Conclusions:

The orbital dysmorphology in unicoronal craniosynostosis is bilateral in nature, and it is not wholly treated with conventional fronto-orbital advancement and remodeling. The severity of ipsilateral orbital dysmorphology is correlated with the incidence of postoperative strabismus following conventional fronto-orbital advancement and remodeling. Future research is needed to develop strategies to mitigate the risk of development of strabismus in this group of patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
A Retrospective Case Series Reporting the Outcomes of Avance Nerve Allografts in the Treatment of Peripheral Nerve Injuries
Authors: Leckenby Jonathan I. , Furrer Curdin , Haug Luzian , Juon Personeni Bettina , Vögelin Esther
Published: December 2019

Background:

Acellular nerve allografts are a viable treatment modality for bridging nerve gaps. Several small studies have demonstrated results equal to those of autologous grafts; however, there is information lacking with regard to outcomes for wider indications. The authors evaluated the outcomes of patients treated with a nerve allograft in a variety of clinical situations.

Methods:

A retrospective chart analysis was completed between April of 2009 and October of 2017. Inclusion criteria were age 18 years or older at the time of surgery and treatment with a nerve allograft. Patients were excluded if they had not been followed up for a minimum of 6 months. The modified Medical Research Council Classification was used to monitor motor and sensory changes in the postoperative period.

Results:

Two hundred seven nerve allografts were used in 156 patients; of these, 129 patients with 171 nerve allografts fulfilled the inclusion criteria. Seventy-seven percent of patients achieved a sensory outcome score of S3 or above and 36 percent achieved a motor score of M3 or above. All patients with chronic pain had improvement of their symptoms. Graft length and diameter were negatively correlated with reported outcomes. One patient elected to undergo revision surgery, and the original graft was shown histologically to have extensive central necrosis. Anatomically, allografts used for lower limb reconstruction yielded the poorest results. All chronic patients had a significantly lower postoperative requirement for analgesia, and allografts were effective in not only reducing pain but also restoring a functional level of sensation.

Conclusions:

This study supports the wider application of allografts in managing nerve problems. However, caution must be applied to the use of long grafts with larger diameters.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Muscle-Sparing Descending Branch Latissimus Dorsi Free Flap for Lower Extremity Reconstruction
Authors: Kurlander David E. , Durand Paul , Couto Rafael A. , Lamaris Gregory A. , Kaza Angela G. , Swanson Marco , Gatherwright James , Kaufman Bram R.
Published: December 2019

Background:

The muscle-sparing descending branch latissimus dorsi muscle (MSLD) flap is a versatile flap with numerous benefits. It is an often overlooked but useful option when considering free flap donors. In this article, the authors present the largest experience with the MSLD flap, with focus on its use in lower extremity reconstruction.

Methods:

Patients undergoing lower extremity reconstruction with the MSLD flap at a single institution from 2012 to 2017 were identified. Patient and wound characteristics, surgical details, complications, and outcomes were examined. Outcomes were compared to a cohort who underwent lower extremity reconstruction with other free muscle flaps during the same period.

Results:

Thirty-six consecutive patients who underwent MSLD flap surgery were identified. Mean follow-up was 18.8 months. Mean body mass index was 29.2 kg/m2 and 56 percent were smokers. The most common wound causes were motor vehicle collision (46 percent) and fall (22 percent). The most common anatomical location was the distal third of the tibia (33 percent). Mean operative time was 380 minutes. Complications included three total losses (8 percent) and one partial loss (3 percent). No donor-site seromas were reported. Four patients required subsequent amputation for orthopedic issues (nonunion/pain). Patients receiving MSLD and other flaps had similar rates of amputation, donor- and recipient-site complications, and ambulation status (p > 0.05).

Conclusions:

The MSLD flap is a useful and reliable option for free flap reconstruction of the lower extremity. Advantages include an easily contourable flap, low revision rate, low complication rate, and the ability to harvest in supine position. In addition, the MSLD flap preserves donor function useful for rehabilitation and minimizes seroma risk.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Amifostine Prophylaxis in Irradiated Breast Reconstruction
Authors: Luby Alexandra O. , Subramanian Chitra , Buchman Lauren K. , Lynn Jeremy V. , Urlaub Kevin M. , Nelson Noah S. , Donneys Alexis , Cohen Mark S. , Buchman Steven R.
Published: December 2019

Background

Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often resulting in delayed or compromised breast reconstruction. Thus, effective yet safe methods of radiation injury prophylaxis would be desirable. Amifostine is a Food and Drug Administration–approved radioprotectant; however, concerns about its potential to also protect cancer remain. The purpose of this study was to evaluate the oncologic safety of amifostine (AMF) in vitro and determine its effect on human breast cancer cells in the setting of XRT.

Methods

One ER+/PR+/Her2− (MCF-7) and two ER−/PR−Her2− (MDA-MB-231, MDA-MB-468) breast cancer cell lines were investigated. Female fibroblasts were used as controls. Cells were treated with WR-1065, the active metabolite of AMF, 20 minutes before 0Gy, 10Gy, or 20Gy XRT. Live and dead cells were quantified; percent cell death was calculated.

Results

WR-1065 treatment significantly preserved viability and reduced healthy female fibroblasts death after XRT compared with untreated controls. All three breast cancer cells lines exhibited radiosensitivity with substantial cell death. Cancer cells retained their radiosensitivity despite WR-1065 pretreatment, achieving the same degree of cell death as untreated controls.

Conclusions

This study demonstrated the proficiency of AMF to selectively protect healthy cells from XRT while breast cancer cells remained radiosensitive. These results support the oncologic safety of AMF in breast cancer in vitro. Further investigation is now warranted in vivo to ascertain the translational potential of using AMF as a radioprotectant to improve breast reconstruction after radiation treatment.
Oblique Plane Cutting of Cone Beam Computed Tomography Analysis on the Safe Zone for Micro-Implants of Maxillary Molar Region
Authors: Wang Chao , Wang Guobao , Xin Ce , You Qingling , Wu Jun
Published: December 2019

Objective:

To explore the safe zone for micro-implants of the maxillary molar region by oblique plane cutting mode of cone beam computed tomography (CBCT).

Methods:

Thirty-nine patients with orthodontic alignment were enrolled with CBCT. In this study, the areas between the maxillary second premolar and the first molar were analyzed by the image reconstruction with CS 3D Imaging Software. The alveolar ridge bone width and the minimum interradicular space were measured at the height of 8, 10, and 12 mm from archwire under the 2 cutting modes of the oblique plane and coronal plane, respectively. The statistical analysis was performed.

Results:

The bone widths of alveolar ridge between the maxillary second premolar and the first molar were statistically significant under the 2 cutting modes of the oblique plane and coronal plane. The bone width was gradually decreased to the cranial side with the fixed measurement point and the interradicular space was gradually increased. The differences were statistically significant.

Conclusion:

The oblique plane cutting of CBCT is more representative of the alveolar bone than the coronal plane. There is sufficient safe zone between the maxillary second premolar and the first molar for most patients to implant the micro-implants. However, the individual differences present large and CBCT needs to be taken before the implantation.
Long-term Survival of 10,116 Korean Live Liver Donors
Authors: Hong Suk Kyun , Choe Sunho , Yi Nam-Joon , Shin Aesun , Choe Eun Kyung , Yoon Kyung Chul , Lee Kwang-Woong , Suh Kyung-Suk
Published: December 2019

Objective:

To evaluate the long-term mortality of Korean live liver donors using data from a national donor registry by comparing it with the mortality of the general population.

Summary of Background Data:

Although live liver donors generally have a healthy status, their long-term mortality has not been properly addressed in a large donor registry.

Methods:

Data of 10,116 live liver donors were drawn from a mandated national registry of Korean live liver donors between 2000 and 2015. Matched controls were selected from the Korean National Health Insurance System-National Sample Cohort (NHIS-NSC). Median (range) follow-up of liver donors was 5.7 (0–15.9) years. Donors were 1:3 individually matched to controls by sex and 5-year age group; potential controls were from the whole NHIS-NSC (Control 1) or from NHIS-NSC after excluding people with contraindications to be organ donors (Control 2) (donor, n = 7538; Control 1, n = 28,248; Control 2, n = 28,248).

Results:

Fifty-three deaths occurred after donation. Ten-year cumulative mortality of live liver donors was 0.9%. The most common cause of death was suicide (n = 19) followed by cancer (n = 9) and traffic accident (n = 7). In the matched control analysis, overall risk of death was significantly lower in donors than in Control 1 (P < 0.001), but higher than in Control 2 (P < 0.001).

Conclusions:

Liver donors have increased long-term mortality risk compared to similar healthy controls without contraindications to be organ donors. Therefore, long-term follow-up, including psychosocial support, is needed for live liver donors.
Idiopathic Intracranial Hypertension and Anemia: A Matched Case–Control Study
Authors: Lin Weijie Violet , Berry Shauna , Nakawah Mohammad Obadah , Sadaka Ama , Lee Andrew G.
Published: December 2019

Background:

An association between idiopathic intracranial hypertension (IIH) and anemia has been speculated from previous case reports and case series. Retrospective studies to date have not used matched case controls to compare standardized complete blood count (CBC) values for the presence of anemia.

Methods:

At our tertiary care facility, 50 patients with IIH were matched with 50 case–control patients to compare CBC values from laboratory affiliates with standardized ranges.

Results:

No significant difference was found for any CBC parameters for IIH vs control patients. For female IIH and control patients as well as male IIH patients, values for red blood cell count, hemoglobin (HGB), and hematocrit (HCT) tended to trend on the lower end of “normal” range, whereas this was not seen in male control patients.

Conclusions:

In this retrospective, matched case–control study, no significant association was found between IIH and anemia when comparing standardized CBC values. In accordance with previous studies, the prevalence of anemia may be relatively higher in the IIH population due to a prominent demographic overlap of females of child-bearing age.
Linguistic generalization and compositionality in modern artificial neural networks
Authors: Baroni Marco
Published: December 2019

In the last decade, deep artificial neural networks have achieved astounding performance in many natural language-processing tasks. Given the high productivity of language, these models must possess effective generalization abilities. It is widely assumed that humans handle linguistic productivity by means of algebraic compositional rules: are deep networks similarly compositional? After reviewing the main innovations characterizing current deep language-processing networks, I discuss a set of studies suggesting that deep networks are capable of subtle grammar-dependent generalizations, but also that they do not rely on systematic compositional rules. I argue that the intriguing behaviour of these devices (still awaiting a full understanding) should be of interest to linguists and cognitive scientists, as it offers a new perspective on possible computational strategies to deal with linguistic productivity beyond rule-based compositionality, and it might lead to new insights into the less systematic generalization patterns that also appear in natural language.

This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
How the brain composes morphemes into meaning
Authors: Gwilliams Laura
Published: December 2019

Morphemes (e.g. [tune], [-ful], [-ly]) are the basic blocks with which complex meaning is built. Here, I explore the critical role that morpho-syntactic rules play in forming the meaning of morphologically complex words, from two primary standpoints: (i) how semantically rich stem morphemes (e.g. explode, bake, post) combine with syntactic operators (e.g. -ion, -er, -age) to output a semantically predictable result; (ii) how this process can be understood in terms of mathematical operations, easily allowing the brain to generate representations of novel morphemes and comprehend novel words. With these ideas in mind, I offer a model of morphological processing that incorporates semantic and morpho-syntactic operations in service to meaning composition, and discuss how such a model could be implemented in the human brain.

This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
No consistent evidence for microbiota in murine placental and fetal tissues
Authors: Theis Kevin R. , Romero Roberto , Greenberg Jonathan M. , Winters Andrew D. , Garcia-Flores Valeria , Motomura Kenichiro , Ahmad Madison M. , Galaz Jose , Arenas-Hernandez Marcia , Gomez-Lopez Nardhy
Published: December 2019

The existence of a placental microbiota andin uterocolonization of the fetus has been the subject of recent debate. The objective of this study was to determine whether the placental and fetal tissues of mice harbor bacterial communities. Bacterial profiles of the placenta and fetal brain, lung, liver, and intestine were characterized through culture, qPCR, and 16S rRNA gene sequencing. These profiles were compared to those of the maternal mouth, lung, liver, uterus, cervix, vagina, and intestine, as well as to background technical controls. Positive bacterial cultures from placental and fetal tissues were rare; of the 165 total bacterial cultures of placental tissues from the 11 mice included in this study, only nine yielded at least a single colony, and five of those nine positive cultures came from a single mouse. Cultures of fetal intestinal tissues yielded just a single bacterial isolate:Staphylococcus hominis, a common skin bacterium. Bacterial loads of placental and fetal brain, lung, liver, and intestinal tissues were not higher than those of DNA contamination controls and did not yield substantive 16S rRNA gene sequencing libraries. From all placental or fetal tissues (N = 49), there was only a single bacterial isolate that came from a fetal brain sample having a bacterial load higher than that of contamination controls and that was identified in sequence-based surveys of at least one of its corresponding maternal samples. Therefore, using multiple modes of microbiologic inquiry, there was not consistent evidence of bacterial communities in the placental and fetal tissues of mice.

IMPORTANCE

The prevailing paradigm in obstetrics has been the sterile womb hypothesis, which posits that fetuses are first colonized by microorganisms during the delivery process. However, some are now suggesting that fetuses are consistently colonized by microorganismsin uteroby microbial communities that inhabit the placenta and intra-amniotic environment. Given the established causal role of microbial invasion of the amniotic cavity (i.e. intra-amniotic infection) in pregnancy complications, especially preterm birth, if thein uterocolonization hypothesis were true, there are several aspects of current understanding that will need to be reconsidered including the magnitude of intra-amniotic microbial load required to cause disease and their potential influence on the ontogeny of the immune system. However, acceptance of thein uterocolonization hypothesis is premature. Herein, we do not find consistent evidence for placental and fetal microbiota in mice using culture, qPCR, and DNA sequencing.
The proteomic inventory reveals the chloroplast ribosome as nexus within a diverse protein network
Authors: Westrich Lisa Désirée , Gotsmann Vincent Leon , Herkt Claudia , Ries Fabian , Kazek Tanja , Trösch Raphael , Ramundo Silvia , Nickelsen Jörg , Armbruster Laura , Wirtz Markus , Storchová Zuzana , Raeschle Markus , Willmund Felix
Published: December 2019

Chloroplast gene expression is tightly regulated and majorly controlled on the level of protein synthesis. Fine-tuning of translation is vital for plant development, acclimation to environmental challenges and for the assembly of major protein complexes such as the photosynthesis machinery. However, many regulatory mediators and the interaction network of chloroplast ribosomes are not known to date. We report here on a deep proteomic analysis of the plastidic ribosome interaction network inChlamydomonas reinhardtiicells. Affinity-purification of ribosomes was achieved via endogenous affinity tagging of the chloroplast-encoded protein Rpl5, yielding a specific enrichment of >650 chloroplast-localized proteins. The ribosome interaction network was validated for several proteins and provides a new source of mainly conserved factors directly linking translation with central processes such as protein folding, photosystem biogenesis, redox control, RNA maturation, energy and metabolite homeostasis. Our approach provided the first evidence for the existence of a plastidic co-translational acting N-acetyltransferase (cpNAT1). Expression of tagged cpNAT1 confirmed its ribosome-association, and we demonstrated the ability of cpNAT1 to acetylate substrate proteins at their N-terminus. Our dataset establishes that the chloroplast protein synthesis machinery acts as nexus in a highly choreographed, spatially interconnected protein network and underscores its wide-ranging regulatory potential during gene expression.

ONE-SENTENCE SUMMARY

Affinity purification ofChlamydomonas reinhardtiichloroplast ribosomes and subsequent proteomic analysis revealed a broad spectrum of interactors ranging from global translation control to specific pathways.
Background selection does not mimic the patterns of genetic diversity produced by selective sweeps
Authors: Schrider Daniel R.
Published: December 2019

1

It is increasingly evident that natural selection plays a prominent role in shaping patterns of diversity across the genome. The most commonly studied modes of natural selection are positive selection and negative selection, which refer to directional selection for and against derived mutations, respectively. Positive selection can result in hitchhiking events, in which a beneficial allele rapidly replaces all others in the population, creating a valley of diversity around the selected site along with characteristic skews in allele frequencies and linkage disequilibrium (LD) among linked neutral polymorphisms. Similarly, negative selection reduces variation not only at selected sites but also at linked sites—a phenomenon called background selection (BGS). Thus, discriminating between these two forces may be difficult, and one might expect efforts to detect hitchhiking to produce an excess of false positives in regions affected by BGS. Here, we examine the similarity between BGS and hitchhiking models via simulation. First, we show that BGS may somewhat resemble hitchhiking in simplistic scenarios in which a region constrained by negative selection is flanked by large stretches of unconstrained sites, echoing previous results. However, this scenario does not mirror the actual spatial arrangement of selected sites across the genome. By performing forward simulations under more realistic scenarios of BGS, modeling the locations of protein-coding and conserved noncoding DNA in real genomes, we show that the spatial patterns of variation produced by BGS rarely mimic those of hitchhiking events. Indeed, BGS is not substantially more likely than neutrality to produce false signatures of hitchhiking. This holds for simulations modeled after both humans andDrosophila, and for several different demographic histories. These results demonstrate that appropriately designed scans for hitchhiking need not consider background selection’s impact on false positive rates. However, we do find evidence that BGS increases the false negative rate for hitchhiking—an observation that demands further investigation.
Non-shared dispersal networks with heterogeneity promote species coexistence in hierarchical competitive communities
Authors: Zhang Helin , Liao Jinbao
Published: December 2019

The competition-colonization trade-off has been a classic paradigm to understand the maintenance of biodiversity in natural ecosystems. However, species-specific dispersal heterogeneities are not well integrated into our general understanding of how spatial coexistence emerges between competitors. Combining both network and metapopulation approaches, we construct a spatially explicit, patch-occupancy dynamic model for communities with hierarchically preemptive competition, to explore species coexistence in shared vs. non-shared dispersal networks with contrasting heterogeneities (including regular, random, exponential and scale-free networks). Our model shows that species with the same demography (i.e. identical colonization and extinction rates) cannot coexist stably in shared networks (i.e. the same dispersal pathways), regardless of dispersal heterogeneity. In contrast, increasing dispersal heterogeneity (even at very low levels of heterogeneity) in non-shared networks can greatly promote spatial coexistence, owing to the segregation-aggregation mechanism by which each species is restricted to self-organized clusters with a core of the most connected patches. However, these competitive patterns are largely mediated by species life-history attributes, for example, a unimodal biodiversity response to an increase of species dispersal rate emerges in non-shared heterogeneous networks, with species richness peaking at intermediate dispersal levels. Interestingly, increasing network size can foster species coexistence, leading to a monotonic increase in species-area curves. This strongly suggests that, unexpectedly, many more species can co-occur than the number of limiting resources. Overall, this modelling study, filling the gap between network structure and spatial competition, provides new insights into the coexistence mechanisms of spatial heterogeneity.