bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of Microarray for the Simultaneous Detection of Common α- and β-Thalassemia Gene Mutations
Authors: Pornprasert Sakorn , Anurak Rinradee , Ruengdit Chedtapak , Pienthai Nattasit , Tookjai Monthathip , Punyamung Manoo , Pongpunyayuen Panida
Published: December 2018

Background

Methods for detecting the complex genetic characteristics of α- and β-thalassemias are required for preventing and controlling the outbreak of new cases.

Methods

We evaluated the accuracy and practical utility of microarray for simultaneous detection of α- and β-thalassemias. A total of 102 DNA specimens, which represented 25 different genotypes, were tested in parallel using the microarray and reference methods used in the thalassemia laboratory of the Associated Medical Sciences–Clinical Services Center (AMS-CSC), Chiang Mai, Thailand.

Results

A total of 100 (98.0%) DNA specimens were completely concordant between the microarray and reference methods, whereas discrepancies between the different methods were observed in only 2 DNA specimens with homozygous hemoglobin E (HbE).

Conclusions

The microarray appeared to be a fast, easy to perform, and accurate method for simultaneous detection of α- and β-thalassemias in Thailand and Southeast Asian countries. However, this technique needs to be improved and validated in a larger number of specimens with homozygous HbE before further routine laboratory use.
Pre- and Postoperative Gait Analysis and Video for Selective Dorsal Rhizotomy in Spastic Diplegia: 2-Dimensional Operative Video
Authors: Archer Jacob , Yaacoub Alan P , Angulo-Parker Francisco , Fritsch Gloria , Riner Shana , Coon Ann , Johnson Sarah K , Delima Sarah , Jea Andrew , Raskin Jeffrey S
Published: December 2018

Severe lower limb spasticity can hinder motor tasks and negatively impacts the quality of life in patients with cerebral palsy. Selective dorsal rhizotomy is a well-established neurosurgical intervention aimed at reducing muscle spasticity in patients with such neuromuscular conditions. Long-term outcomes of selective dorsal rhizotomy have been promising among the authors’ institutional series of patients. In this case, we demonstrate the use of L1-S1 osteoplastic laminoplasty and L1-S1 selective dorsal rhizotomy in a 5-year-old male patient with cerebral palsy and spastic lower extremity diplegia. Favorable selection criteria for this case included disabling lower extremity diplegia, young age, good core strength, no cognitive delay, and strong rehabilitation potential. The patient's preoperative functional status was noncommunity ambulator (Gross Motor Function Classification System Level III) with walker use and good dynamic balance. Prior to the procedure, he demonstrated an overall decreased muscle strength in bilateral lower extremities with bilateral hamstring spasticity (Ashworth 3) and bilateral heel cord spasticity (Ashworth 4).

Rhizotomy was performed with identification and selective sectioning of dorsal nerve roots with abnormal stimulation patterns. Fibers with unsustained discharge of appropriate muscles were identified and spared. No intraoperative or postoperative complications were encountered. The patient had minimal back pain and surgical morbidity postoperatively. Following the procedure and highly structured inpatient and outpatient rehabilitation therapies, the patient exhibited significant improvement in gait velocity (84%) and gait cadence (66%) at 5 months. Additionally, the patient demonstrated greater independence of activities of daily living and improvements in mobility by Pediatric Evaluation Disability Index.

Patient consent was obtained from the parent.
CORRELATIONS BETWEEN EXPERIMENTAL MYOPIA MODELS AND HUMAN PATHOLOGIC MYOPIA
Authors: Vutipongsatorn Kritchai , Nagaoka Natsuko , Yokoi Tae , Yoshida Takeshi , Kamoi Koju , Horie Shintaro , Uramoto Kengo , Hirata Akira , Occelli Laurence M. , Petersen-Jones Simon M. , Montiani-Ferreira Fabiano , Cases Olivier , Kozyraki Renata , Jonas Jost B. , Ohno-Matsui Kyoko
Published: December 2018

Purpose:

To analyze the hallmark features of pathologic myopia developed in animal models and compare them with those seen in patients.

Methods:

A literature review was performed to identify animal models that exhibited key features of pathologic myopia, namely posterior staphyloma, myopic maculopathy, lacquer cracks, and choroidal neovascularization, either spontaneously or induced by monocular deprivation. Using imaging modalities, such as optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein angiography, and electron microscopy, these features were compared with those found in myopic maculopathy of patients.

Results:

Three types of animals were identified. The LRP2 knockout mice exhibited posterior staphylomas and chorioretinal atrophy at 21 and 60 days after birth, respectively. Retinopathy globe enlarged (rge) chicks and normal lid-sutured chicks developed lacquer cracks and chorioretinal atrophy. Lacquer cracks detected in rge chicks subsequently progressed to patchy chorioretinal atrophy, which is also commonly seen in patients with pathologic myopia.

Conclusion:

The LRP2 knockout mice, retinopathy globe enlarged (rge) chicks, and normal lid-sutured chicks exhibit features typical for myopic maculopathy in patients and could serve to further elucidate the pathogenesis of myopic maculopathy.
Prevalence of migraine in Han Chinese of Fujian province
Authors: Lin Qi-fang , Xia Qiao-qing , Zeng Yu-li , Wu Xiao-yang , Ye Lin-feng , Yao Long-teng , Xin Yong-tong , Huang Gen-bin
Published: December 2018

Migraine is a relatively common disease that is associated with high disability and reduced quality-of-life. This study aimed to investigate the prevalence, epidemiological characteristics, and risk factors of migraine in Han Chinese from Fujian Province, China.

A cross-sectional epidemiological survey study was conducted to evaluate characteristics of migraine in Han Chinese. Demographic and clinical data were collected through a survey administered in face-to-face interviews by trained investigators, and a physical exam and symptom review were performed. Univariate and multivariate regression analyses were performed to assess independent risk factors for migraine.

A total of 7860 subjects aged 15 years and older were surveyed, of which 9.1% (n = 717) were diagnosed with migraine. Among these, a higher percentage was female (12.6%) than male (5.3%). Only 114 subjects (15.9%) were diagnosed as having migraine with aura, which was closely associated with family history of migraine. Multivariate regression analysis showed that the odds of migraine were significantly lower in subjects aged ≥50 years compared with those aged <30 years (odds ratio [OR] ranged from 0.40 to 0.64; P ≤.013) and was higher in females compared with males (OR = 2.89, P <.001). The odds of migraine was significantly greater in subjects with a history of alcohol consumption (OR = 1.81, P <.00) and insomnia (OR = 2.77, P <.001).

Han Chinese in Fujian province has a relatively high prevalence of migraine, and female gender, <50 years of age, insomnia, and use of alcohol are associated with increased odds of having migraine in this population.
Effectiveness of neuromuscular electrical stimulation therapy in patients with urinary incontinence after stroke
Authors: Guo Gai-yan , Kang Yong-gang
Published: December 2018

Background:

This study aimed to evaluate the effectiveness of neuromuscular electrical stimulation (NMES) therapy in patients with urinary incontinence after stroke (UIAS).

Methods:

A total of 82 patients with UIAS were randomly assigned to 2 groups that received NMES therapy (NMES group) or sham NMES (sham group) for 10 weeks. The primary efficacy endpoints were measured by urodynamic values, and Overactive Bladder Symptom Score (OABSS). The secondary efficacy endpoints were assessed by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score, Barthel Index (BI) scale, and adverse events. All outcomes were evaluated at baseline and at the end of 10 weeks treatment.

Results:

After 10-week treatment, the patients received NMES therapy showed better efficacy in primary endpoints of urodynamic values (P <.01) and OABSS (P <.01), and secondary endpoints of ICIQ-SF (P <.01) and BI (P <.01), compared with patients who underwent sham NMES. No adverse events were recorded in both groups.

Conclusions:

In summary, we demonstrated that 10 weeks of NMES therapy was efficacious in patients with UIAS.
A pilot study of acupuncture at pain acupoints for cervical cancer pain
Authors: Meng Fan-feng , Feng Yan-hong
Published: December 2018

This retrospective study aimed to investigate the feasible effectiveness of acupuncture at pain acupoints for the treatment of patients with cervical cancer pain (CCP). A total of 64 cases were analyzed. All these cases were assigned to an acupuncture group or a control group according to the different therapies they received. The cases in the acupuncture group received acupuncture treatment at pain acupoints, while the subjects in the control group underwent acupuncture at regular acupoints. The primary endpoint was CCP, assessed by numeric rating scale (NRS). The secondary endpoints were evaluated by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and Karnofsky Performance Status (KPS). In addition, adverse events were also recorded during the treatment period. After treatment, patients in the acupuncture group exerted greater outcomes in CCP reduction when compared with patients in the control group (P < .01). In addition, no adverse events were recorded in either group. The results of this study showed that acupuncture at pain acupoints might be efficacious in patients with CCP after 14-day treatment.
Desmoplastic fibroma of the femur with atypical image findings
Authors: Xu Yongming , Wang Yaoting , Yan Jun , Bai Xiaodong , Xing Gengyan
Published: December 2018

Rationale:

Desmoplastic fibroma of the bone (DFB) is an extremely rare benign bone tumor, which can occur in any bone at all ages. Herein, we report a case of non-specific imaging findings.

Patient concerns:

A 25-year-old female patient was consulted in the Armed Police General Hospital (Beijing, China) due to repeated pain in the right thigh lasting over 1 year. Imaging examination revealed a space-occupying lesion in the right femur.

Diagnosis:

Desmoplastic fibroma of the femur

Interventions:

Wide surgical resection

Outcomes:

At the 1-year follow-up visit, no relapse in the tumor was observed.

Lessons:

In this case report, we described and emphasized the particularity of the case examined and the possible non-specificity of the imaging results of some DFB cases.
Age-specific and gender-dependent impact of primary headache disorders on dementia risk
Authors: Yin Jiu-Haw , Tsai Chia-Lin , Lee Pei-Jung , Chou Chung-Hsing , Chen Shao-Yuan , Chung Chi-Hsiang , Chien Wu-Chien , Lin Chun-Chieh , Sung Yueh-Feng , Yang Fu-Chi , Tsai Chia-Kuang , Lee Jiunn-Tay
Published: December 2018

Dementia is a global burden of public health. Headache disorders are the third most common cause of disability worldwide and common problems in the elderly population. Few studies focused on the relationship between primary headache disorders (PHDs) and cognitive status, and the results remain controversial. The aim of this countrywide, population-based, retrospective study was to investigate potential association between PHDs and dementia risk.

We enrolled 1346 cases with PHDs to match the 5384 individuals by age, gender and co-morbidities. The definition of PHDs, dementia, and risk factors of dementia was identified according to The International Classification of Diseases, Ninth Revision, Clinical Modification. Cox regression was administered for estimating hazard ratios (HR) for dementia.

During more than 5 years of follow-up, PHDs individuals had 1.52 times (P <.05) greater risk to develop all dementia compared with individuals without PHDs. Elderly (aged ≥65 years) patients with PHDs displayed significantly higher risk to develop all dementia (P <.01) and non-Alzheimer non-vascular dementia (NAVD) P <.01). Female PHDs individuals were at higher risk of suffering from all dementia (P <.05) and NAVD (P <.05). The influence of PHDs on all dementia was highest in the first 2 years of observation.

The results indicated PHDs are linked to a temporarily increased risk for dementia, mainly NAVD, with age-specific and gender-dependent characteristics.
CDC20 overexpression leads to poor prognosis in solid tumors
Authors: Wang Shengjie , Chen Borong , Zhu Zhipeng , Zhang Liang , Zeng Junjie , Xu Guoxing , Liu Gang , Xiong Disheng , Luo Qi , Huang Zhengjie
Published: December 2018

Background:

A plenty of previous researches have reported the prognostic value of CDC20 (Cell Division Cycle Protein 20) in solid tumors. Nevertheless, these researches were restricted by the small sample databases and the results were not strongly consistent among them.

Methods:

We comprehensively searched these relevant studies by PubMed, Web of Science, and EMBASE, in which publications before March 2017 were included. Pooled HR values for OS were cumulatively pooled and quantitatively analyzed in the meta-analysis.

Results:

Hence we composed a meta-analysis based on 8 studies with 1856 patients in order to assess the potential relationship between CDC20 overexpression and OS (overall survival) in human solid tumors. There were a total of 8 studies (n = 1856) assessed in the meta-analysis. What suggested in both univariate and multivariate analysis for survival is that high level of CDC20 expression apparently pointed to poor prognosis. In the univariate analysis, the combined hazard ratio (HR) for OS was 1.75 (95% confidence interval [CI]: 1.07–2.86, P = .03). The pooled HR of multivariate analysis for OS was 2.48 (95% confidence interval [CI]: 2.10–2.94, P < .001).

Conclusions:

The meta-analysis indicated that high level of CDC20 expression is significantly correlated with decreased survival in most case of human solid tumors. In addition, CDC20 shows promise as a meaningful prognostic biomarker and original therapeutic target, on the basis of its expression level in solid tumors.
Postural control and balance in a cohort of healthy people living in Europe
Authors: Patti Antonino , Bianco Antonino , Şahin Neşe , Sekulic Damir , Paoli Antonio , Iovane Angelo , Messina Giuseppe , Gagey Pierre Marie , Palma Antonio
Published: December 2018

In the past 20 years, posturography has been widely used in the medical field. This observational study aimed to report the values derived from posturography of a wide set of healthy subjects from various European countries using a plantar pressure platform and a standardized method of measurement.

A random cluster sampling of 914 healthy subjects aged between 7.0 and 85.99 years, stratified by age, was carried out. To provide percentile values of our cohort, data were processed to obtain 3 curves corresponding to the following percentiles: 25th, 50th, 75th, and the interquartile range. Distance-weighted least squares method was used to represent the percentile on appropriate graphs.

In our sample, the balance to improve with age, up to approximately 45 years, but the trend to reverse with older age. The data show that the oscillations on the sagittal plane (y-mean) change with advancing age. Young people had more retro-podalic support than older people; the balance shifted forward in elderly people.

As the study included a relatively large quantity of data collected using a standardized protocol, these results could be used as normative values of posturography for similar populations. On the basis of this data, correct diagnostic clues will be available to clinicians and professionals in the field. However, further studies are needed to confirm our findings.
Single level discectomy with and without disc prosthesis
Authors: Çakir Tayfun , Çakir Mürteza , Okay Hilmi Önder , Yolaş Coşkun , Tanriverdi Osman , Ömeroğlu Muhammed , Arslan Yusuf Kemal
Published: December 2018

Background:

Low back and leg pain due to lumbar discal hernia (LDH) is an important health issue. Current evidences support surgery in carefully selected patients who have failed conservative treatment and do not exhibit any psychosocial overlay. However, as known, sometimes it may be still very difficult to normalize the life qualities of patients for long times. Now different surgical methods for LDH are in use with new technological materials. One of them is lumbar disc prosthesis. In this study, the radiological and clinical effects of using lumbar disc prosthesis were evaluated with comparing patients underwent simple lumbar microdsicectomy. The purpose of this study is to reveal whether inserting the disc prosthesis into the intervertebral distance after lumbar microdiscectomy is beneficial or not both radiologically and clinically.

Methods:

A total of 114 patients were analyzed; the first cohort consisted of 57 patients who received a lumbar discectomy at a single level along with the implantation of a disc prosthesis and the second consisted of 57 patients only received a lumbar discectomy at a single level. These 2 groups were studied by comparing the disc space on the level of carried out operations with pain scales, foramen diameters of coming about related roots preoperatively and postoperatively at 3 years.

Results:

One of the significant results of the implementation of the disc prosthesis is fulfilment of a healthy disc height again after microdiscectomy due to LDH. We concluded that fulfilment of a healthy disc height with lumbar disc prosthesis was clinically beneficial for patients underwent microdiscectomy.

Conclusions:

Based on the results obtained in this study, it can be concluded that the implantation of a disc prosthesis in appropriate patients is more favorable regarding pain and spinal physiology when compared to simple microdiscectomy.
Clinical and molecular characterization of early T-cell precursor acute lymphoblastic leukemia
Authors: Wang Xiao-Xue , Wu Danyang , Zhang Lijun
Published: December 2018

Rationale:

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a small subtype of T-cell acute lymphoblastic leukemia with a typical immune-phenotype: lack of T-lineage cell surface markers CD1a and CD8 expression, weak or absent CD5 expression, at least one of the myeloid or hematopoietic stem cell markers. It is characterized by high rate of induction failure and the effective unified treatment strategies are still indeterminate. We present 2 ETP-ALL cases.

Patient concerns:

A 42-year-old man presented with abnormal hemogram for 4 months, intermittent fever for 2 months and cough for 1 week. A 27-year-old woman was admitted to the hospital for a fever and headache for that had persisted for 1 week.

Diagnosis:

The peripheral blood examination, the bone marrow aspiration and flow cytometry for both patients revealed ETP-ALL.

Interventions:

Both cases accepted chemotherapy including cytarabine.

Outcomes:

In case one, the patient reached complete hematological remission with negative minimal residual detected by flow cytometry after the first circle of chemotherapy. In case 2, the patient received complete remission after the second circle of chemotherapy with high doses of cytarabine.

Lessons:

The application of the high-dose cytarabine in induction chemotherapy of ETP-ALL can bring better outcome. ETP-ALL with myeloid features may benefit from therapies used in myeloid malignancies.
Factors affecting labor duration in Chinese pregnant women
Authors: Chen Hongqin , Cao Liyuan , Cao Wen , Wang Hui , Zhu Cairong , Zhou Rong
Published: December 2018

The aim of the study was to explore the role of parity, maternal age, medical interventions, and birth weight with respect to labor duration and cervical dilation.

A total of 1601 pregnant women who had a singleton term gestation, spontaneous onset of labor, vertex presentation, vaginal delivery, and a normal perinatal outcome were reviewed. The retrospective study was conducted in patients from West China Second University Hospital of Sichuan University during June 2008 to June 2013.

There were 1367 nulliparous women and 234 multiparous women analyzed. The first stage (8.3 ± 3.8 vs 5.0 ± 2.6 hours), latent phase (5.1 ± 3.2 vs 3.5 ± 2.4 hours), active phase (3.2 ± 1.8 vs 1.5 ± 1.0 hours), second stage (44 ± 31 vs 18 ± 14 minutes), and total stage of labor (9.1 ± 3.9 vs 5.4 ± 2.6 hours) were all longer in nulliparous than in multipara women (all P < .05); but no significant difference in the third stage of labor (both 7 ± 4 minutes). In nulliparous women, the average time of first stage of labor increased by 58.257, 171.443, and 56.581 minutes due to artificial rupture of membranes, labor analgesia, and birth weight increased by 1 kg, respectively, but it decreased to 63.592 minutes by oxytocin usage, and the difference was significant. The average time of first stage of labor in nulliparous women aged from 26 to 30 years increased by 2.356 minutes compared to one in 20 to 26 years, but it increased by 1.802 minutes to the one in 30 to 39 years, compared to 20 to 26 years and the difference was not significant. The results were basically similar after multipara women were included.

Labor was significantly shorter in multiparous women than that in nulliparous women. Increased birth weight significantly increased in the length of the active phase and the second stage among nulliparous women. The increase of age, artificial rupture of membranes, labor analgesia, and the increase of birth weight tends to increase the time of first stage of labor and total labor duration, whereas oxytocin could shorten it.
1,25-dihydroxyvitamin-D3 promotes neutrophil apoptosis in periodontitis with type 2 diabetes mellitus patients via the p38/MAPK pathway
Authors: Tang Yaping , Liu Junyu , Yan Yanmei , Fang Hui , Guo Chengwei , Xie Ruidi , Liu Qi
Published: December 2018

Background

Abnormal neutrophils are involved in many chronic endocrine diseases, including type 2 diabetes mellitus (T2DM), and in periodontitis (PD), which is a chronic inflammatory disease in which neutrophils play a vital role. The p38 mitogen-activated protein kinase (MAPK) signaling pathway participates in the apoptosis of many inflammatory cells. Additionally, 1,25-dihydroxyvitamin-D3 (1,25VitD3) as a regulator can induce responses to infection and tumor cell apoptosis. However, the effect of 1,25VitD3 in the pathogenic relationship between T2DM and PD remains unclear. The aim of this study was to assess the effect of 1,25VitD3 on neutrophil apoptosis in patients with T2DM and PD and the p38-MAPK-relevant signaling pathway mechanism in this process in vitro.

Methods

Neutrophils were stained with Wright's stain, and apoptosis was detected by flow cytometry and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Apoptosis- and p38-related mRNAs and proteins were examined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting and ELISA. The internal relationships were analyzed using a linear regression equation and Pearson's correlation coefficient.

Results

The highest rate of neutrophil apoptosis occurred in cultures treated with 10–8 mol/L 1,25VitD3 in the T2DM-PD group. The apoptosis rate in the T2DM-PD-p38 inhibitor group was higher than that in the healthy control group. Western blot, ELISA and qRT-PCR results showed that the mRNA and protein expression profiles of Caspase-3 and Bax were highly up-regulated and that Bcl-2 was down-regulated in the T2DM-PD-p38 inhibitor group. The expression levels of apoptotic mRNAs and proteins in the T2DM and T2DM-PD groups were significantly higher than those in the T2DM-p38 and T2DM-PD-p38 inhibitor groups. 1,25VitD3-induced neutrophil apoptosis and phosphorylated p38 (p-p38) expression were partially inhibited by the p38 inhibitor. Expression levels of apoptosis-related genes and p-p38 in neutrophils were positively associated with increasing concentrations of 1,25VitD3. p-p38 protein expression was positively associated with the level of serum 1,25VitD3.

Conclusion

1,25VitD3 could promote peripheral blood neutrophil apoptosis in patients with T2DM and PD through activation of the p38-MAPK signaling pathway in vitro.
Carpal tunnel syndrome caused by synovial osteochondromatosis of the finger flexor tendon
Authors: Kwon Dong Rak , Chae SeungBum , Moon Yong Suk , Woo In Ho
Published: December 2018

Rationale:

Carpal tunnel syndrome (CTS) is the most common peripheral nerve neuropathy resulting from compression of the median nerve as it traverses the carpal tunnel. The pathophysiology of this condition is multifactorial, and majority of cases of CTS are idiopathic. We report cases of CTS caused by synovial osteochondromatosis (SOC), which has rarely been reported.

Patient concerns:

A 45-year-old female was admitted to the clinic due to right hand tingling sensation for 4 months. On physical examination, the patient's symptoms and signs corresponded to the median nerve entrapment at wrist. However, there is mild swelling and tenderness around the second metacarpal bone. Pain was aggravated during wrist and finger flexion.

Diagnoses:

An electrodiagnostic study revealed CTS. She was advised to begin splinting the hand using a wrist brace and to undergo physiotherapy. After 2 weeks, the tingling sensation decreased slightly. However mild swelling and tenderness around the second metacarpal bone did not improve. Ultrasonography showed multiple echogenic foci. Magnetic resonance imaging (MRI) revealed a nodule at the proximal metacarpal level with synovial thickening, enhancement, and a calcified shadow close to the flexor tendon. After confirming the presence of an osseous nodule with synovial thickening, the patient underwent surgery

Interventions:

Carpal tunnel release and mass excision with synovectomy of the adjacent structures were performed. Histologically, the lesion was compatible with a diagnosis of SOC.

Outcome:

The symptoms have improved.

Lessons:

CTS due to SOC on finger flexor tendon is rare but should be considered for possible etiology. Appropriate clinical examination, plain radiography, ultrasonography, and MRI will help physicians to diagnose this condition. In this paper, we report the successful diagnosis and treatment of CTS caused by SOC within the finger flexor tendon.
Trends in Infusion Administrative Practices in US Health Care Organizations: An Exploratory Analysis
Authors: Pratt Benjamin R. , Dunford Benjamin B. , Alexander Mary , Morgeson Frederick P. , Vogus Timothy J.
Published: December 2018

While specialized infusion clinical services remain the standard of care, widespread curtailing and disbanding of infusion teams as a cost-cutting measure has been documented in health care organizations for nearly 2 decades. Owing to this trend, as well as recent government interventions in medical error control, the authors engaged in an exploratory study of infusion administration practices in the US health care industry. This article presents the authors' exploratory findings, as well as their potential implications.
Targeted Molecular and Immunohistochemical Analyses of Endometrial Clear Cell Carcinoma Show that POLE Mutations and DNA Mismatch Repair Protein Deficiencies Are Uncommon
Authors: Baniak Nick , Fadare Oluwole , Köbel Martin , DeCoteau John , Parkash Vinita , Hecht Jonathan L. , Hanley Krisztina Z. , Gwin Katja , Zheng Wenxin , Quick Charles M. , Jarboe Elke A. , Liang Sharon X. , Kinloch Mary
Published: December 2018

Endometrial clear cell carcinoma (ECCC) is an uncommon histotype without unique identified molecular alterations. Recently, The Cancer Genome Atlas molecular subtypes have been reported in ECCC. ECCC cases were collected from 11 institutions with diagnoses confirmed by morphologic review and immunohistochemistry. DNA mismatch repair (MMR) proteins, p53 expression, and ARID1A expression was assessed by immunohistochemistry on tissue microarrays. Targeted next-generation sequencing was completed for POLE, TP53, KRAS, and PIK3CA. Pathogenicity of mutations was determined using MutationTaster and PolyPhen databases. For p53, immunohistochemistry and sequencing were complimentarily used to assess the p53 status. Of 57 cases, 46 were considered prototypical ECCC by morphology and immunohistochemical profile (Napsin A-positive and ER-negative). Three cases were excluded because of insufficient sample for complete immunohistochemical analysis, and 6 had failed sequencing, resulting in 37 cases. Of the 37 remaining cases, 6/37 (16%) had predicted pathogenic mutations in the exonuclease domain of POLE with an allelic frequency >10%; however, no hot-spot mutations were identified. No cases were MMR-deficient. The gene most commonly affected was TP53 (59%, 22/37), followed by KRAS (13%, 2/15) and PIK3CA (13%, 2/15). The current study is the largest molecular analysis of pure ECCC reported to date. When strict classification criteria are applied, MMR-deficient and POLE mutated subtypes are not represented. Further consensus on what represents a deleterious POLE mutations is needed. The findings support separately studying histologically/immunohistochemically defined ECCC to identify characteristic molecular alterations in future studies.
Acetyl-l-Carnitine to Enhance Nerve Regeneration in Carpal Tunnel Syndrome: A Double-Blind, Randomized, Controlled Trial
Authors: Curran Matthew W. T. , Morhart Michael J. , Olson Jaret L. , Hachisuka Akiko , Chan K. Ming
Published: December 2018

Background:

Carpal tunnel syndrome is very common. Although surgery is effective in mild and moderate cases, recovery is often incomplete in severe cases. Therefore, adjuvant therapy to improve nerve regeneration in those patients is much needed. Acetyl-l-carnitine has been shown to be effective in other neuropathies. The goal of this study is to test the hypothesis that acetyl-l-carnitine can promote nerve regeneration and improve function in patients with severe carpal tunnel syndrome.

Methods:

In this proof-of-principle, double-blind, randomized, placebo-controlled trial, adults with severe carpal tunnel syndrome were randomized to receive 3000 mg/day of acetyl-l-carnitine orally or placebo following carpal tunnel release surgery for 2 months. Outcomes were assessed at baseline and at 3, 6, and 12 months postoperatively. Symptom severity and functional outcomes were assessed using the Boston Carpal Tunnel Questionnaire and a wide range of physiologic and functional outcome measures. Patient safety was monitored by physical examination, blood work, and serum drug levels. The outcomes were analyzed using repeated measure two-way analysis of variance.

Results:

Twenty patients with similar baseline characteristics were assigned randomly to the treatment or placebo group in a 1:1 ratio. Sixty percent were women with a mean age ± SD of 59 ± 2. The treatment was safe with no major adverse events reported. Although patients in both groups showed improvements postoperatively, there was no significant difference in any of the outcome measures between the groups.

Conclusion:

Although acetyl-l-carnitine was well tolerated, it did not improve nerve regeneration or functional recovery in patients with severe carpal tunnel syndrome.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
A New Approach to an Old Flap: A Technique to Augment Venous Drainage from the Paramedian Forehead Flap
Authors: Wiener Martin , Karunanithy Narayan , Pease Natalie , Davies Andrew , Walker Nolan , Katsanos Konstantinos , Aldridge Ben , Healy Ciaran
Published: December 2018

The paramedian forehead flap is commonly used in nasal reconstruction, and survival of the distal part of the flap is usually essential for a good cosmetic outcome. Venous congestion leading to tissue necrosis is a recognized complication with this flap. The standard paramedian forehead flap is designed with a number of aims. These are to include the supratrochlear artery, to maximize mobility of the flap pedicle, to maximize the reach of the flap, and to minimize cosmetic implications at the donor site. The supratrochlear artery does not possess sizable venae comitantes; thus, the main pathway for venous drainage of the paramedian forehead flap is through superficial veins. The pattern and location of the superficial veins varies and therefore a standard skin pedicle design cannot be expected to always include sufficient veins to prevent venous congestion and subsequent flap necrosis. This article demonstrates the superficial venous anatomy of the forehead using computed tomographic venography, clinical demonstration, and cadaveric dissection, and describes a technique that can be carried out to augment flap venous drainage by performing careful dissection to identify additional superficial veins at the margins of the flap skin pedicle. One or more veins can then be mobilized and included with the flap pedicle to augment its venous drainage. Use of this technique should lead to a lower incidence of flap necrosis secondary to venous congestion.
Promotion of Primary Murine Breast Cancer Growth and Metastasis by Adipose-Derived Stem Cells Is Reduced in the Presence of Autologous Fat Graft
Authors: Gebremeskel Simon , Gencarelli John , Gareau Alison J. , Levatte Terry , Dugandzic, B.Sc. Anton , Johnston Brent , Bezuhly Michael
Published: December 2018

Background:

Cell-assisted lipotransfer involves enrichment of autologous fat with supraphysiologic numbers of adipose-derived stem cells to improve graft take. Adipose-derived stem cells have been shown to promote cancer progression, raising concerns over the safety of adipose-derived stem cells and cell-assisted lipotransfer in postoncologic breast reconstruction. The authors compared the effect of adipose-derived stem cells alone, cell-assisted lipotransfer, and conventional fat grafting on breast cancer growth and metastasis.

Methods:

Proliferation and migration of murine 4T1 breast cancer cells cultured in control medium or mouse adipose-derived stem cell– or fat graft–conditioned medium were assessed by flow cytometry and scratch assay, respectively. Transcription levels of arginase-1, transforming growth factor-β, and vascular endothelial growth factor were assessed in adipose-derived stem cells and fat graft by quantitative reverse transcription polymerase chain reaction. An orthotopic mouse tumor model was used to evaluate breast cancer progression and metastasis. 4T1 cells were injected into the mammary pad of female BALB/c mice. Six days later, tumors were injected with saline, adipose-derived stem cells, fat graft, or cell-assisted lipotransfer (n = 7 per group). Two weeks later, primary tumors were examined by immunohistochemistry and lung metastasis was quantified.

Results:

Adipose-derived stem cell–conditioned medium increased cancer cell proliferation (p = 0.03); migration (p < 0.01); and transcription of arginase-1, transforming growth factor-β, and vascular endothelial growth factor compared to fat graft–conditioned or control medium (p < 0.02). Tumor-site injection with adipose-derived stem cells alone led to increased primary tumor growth and lung metastasis compared to control, fat graft, or cell-assisted lipotransfer groups (p < 0.05). Adipose-derived stem cell injection increased CD31+ vascular density in tumors (p < 0.01).

Conclusion:

Adipose-derived stem cells alone, but not conventional fat graft or cell-assisted lipotransfer, promote breast cancer cell proliferation and invasiveness in vitro and in vivo.
Nasal Dorsal Augmentation with Freeze-Dried Allograft Bone: 10-Year Comprehensive Review
Authors: Clark Richard P. , Pham Phuong M. , Ciminello Frank S. , Hagge Rosalie J. , Drobny Sarah , Wong Granger B.
Published: December 2018

Background:

The aim of this study was to evaluate freeze-dried cortical allograft bone for nasal dorsal augmentation. The 42-month report on 18 patients was published in 2009 in Plastic and Reconstructive Surgery with 89 percent success at level II evidence, and this article is the 10-year comprehensive review of 62 patients.

Methods:

All grafts met standards recommended by the American Association of Tissue Banks, the U.S. Food and Drug Administration, and the Centers for Disease Control and Prevention. Objective evaluation of the persistence of graft volume was obtained by cephalometric radiography, cone beam volumetric computed tomography, and computed tomography at up to 10 years. Vascularization and incorporation of new bone elements within the grafts were demonstrated by fluorine-18 sodium fluoride positron emission tomography at up to 10 years. Subjective estimation of graft volume persisting up to 10 years was obtained by patient response to a query conducted by an independent surveyor.

Results:

The authors report objective proof of persistence of volume alone or combined with proof of neovascularization in 16 of 19 allografts. The authors report the patient’s subjective opinion of volume persistence in 37 of 43 grafts. The dorsal augmentation was assessed overall to be successful in 85 percent of 62 patients evaluated between 1 and 10 years, with a mean of 4.7 years.

Conclusions:

Freeze-dried allograft bone is a safe and equal alternative for dorsal augmentation without donor-site morbidity. Further studies are needed to (1) confirm these findings for young patients needing long-term reconstruction, and (2) partially demineralize allograft bone to allow carving with a scalpel.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
In Vivo Analysis of Urinary Stones With Dual-Energy Computed Tomography
Authors: Erdogan Hasan , Temizoz Osman , Koplay Mustafa , Ozturk Bahadir
Published: December 2018

Objective

Formation mechanisms and treatment of the urinary stones are different, depending on their chemical structure. Therefore, determining the stone type plays a key role in planning treatment and preventive measures. Computed tomography (CT), with the use of dual-energy technology in recent years, has made it possible to do in vivo analysis of urinary stones. In this study, we aimed to evaluate the diagnostic efficacy of dual-energy CT (DECT) and compare its results with in vitro analysis, which is accepted as a gold standard for analysis of urinary stones.

Materials and Methods

The DECT examinations were performed on 373 patients using 128-slice dual-source CT scanner. Analysis of attenuation ratios in the high and low kilovoltage peak values of the stone was performed at workstation, and stones were classified as hydroxyapatite, calcium oxalate, cystine, and uric acid. On follow-up, the stone was obtained in 35 patients as a result of surgery or passed spontaneously. The DECT analysis and in vitro analysis results were compared and statistically evaluated.

Results

In all patients, 136 hydroxyapatite, 160 calcium oxalate, 57 uric acid, and 20 cystine stones were detected with DECT. In vitro analyses of the stones were performed in 35 patients, and 8 hydroxyapatite, 18 calcium oxalate, 6 uric acid, and 3 cystine stones were revealed. When DECT analysis results were compared with in vitro analysis results, stone types were detected correctly in 32 (91.4%) patients and incorrectly in 3 (8.6%) patients. Especially all uric acid and cystine stones were correctly detected with DECT.

Conclusions

With advanced postprocess analysis methods, DECT is able to analyze urinary stones. The DECT is found superior especially in detecting uric acid and cystine stones. Its success in detecting hydroxyapatite and calcium oxalate stones is also high. When in vivo analyses of the stones are performed with DECT, it will be possible to make a contribution to the personalization and optimization of the treatment.
Early Versus Late Conversion From Immediate to Prolonged-Release Tacrolimus After Renal Transplantation: Clinical Effects and Treatment Costs
Authors: Mendonça Luís , Diniz Hugo , Silvano José , Marques Sofia , Sampaio Susana , Pestana Manuel
Published: December 2018

Introduction

Prolonged-release tacrolimus (PR-TAC) was associated with improved renal function after transplantation when compared to immediate-release tacrolimus (IR-TAC) although evidence is still scarce. This study aimed to compare clinical outcomes and treatment costs in patients who converted from IR-TAC to PR-TAC during the first year after renal transplantation (RT) (early converters [EC]) or after that period (late converters [LC]).

Methods

We performed a retrospective study including 79 patients (EC, 39; LC, 41) which were followed up over 60 months. A mixed-effects approach was used to investigate the differences between both groups regarding renal and metabolic outcomes as well as treatment costs.

Results

The median time from RT to conversion was 3 months for EC and 25 months for LC. For both EC and LC, a significant increase in estimated glomerular filtration rate was observed after conversion (5.2 and 4.9 mL/min per 1.73 m2, respectively). During the first year after RT, EC presented a higher estimated glomerular filtration rate and inferior tacrolimus trough levels when compared to LC, with higher mean treatment costs associated. However, thereafter, these outcomes were similar between groups over the remaining time. At the end of follow-up, no significant differences were found regarding allograft acute rejection (2.6% and 2.4%), new-onset diabetes (15.7% vs 12.2%) or cardiovascular events (5.2% vs 7.3%).

Conclusions

There was a significant benefit on renal function after conversion from IR-TAC to PR-TAC. During the first year after RT, EC presented improved renal function, but higher treatment costs. None of these differences persisted at the end of follow-up.
Poly‐criminal Pirates and Ballooning Effects: Implications for International Counter‐piracy
Authors: Jacobsen Katja Lindskov
Published: December 2018

In view of continued international counter‐piracy efforts and these recent incidents, this article takes the five obstacles presented by Percy and Shortland (2013), as its point of departure for an analysis of key developments of importance for Somali piracy since 2013. Specifically, the article firsts offer an analysis and updated version of Percy and Shortland's five obstacles. Second, I argue, that a sixth obstacle should be added. This obstacle is the phenomenon that practitioners as well as academics working with organised crime refer to as ‘poly‐criminals’. Having elaborated on this additional obstacle – with reference to interviews conducted with key actors in Somalia – the third section explicates the policy impact of poly‐criminal pirates; it offers a discussion of what this alternative conception means for external actors’ counter‐piracy engagements, with particular attention to the risk of creating ‘balloon effects’ when addressing a challenge of this kind (poly‐criminals) through too narrowly defined counter‐piracy lenses, mandates and programmes.
Age‐related histomorphometric and immunohistochemical changes of the moderator band in Egyptian Baladi cattle
Authors: Emam Mahmoud Abdelghaffar , Abo‐Ahmed Ahmed I.
Published: December 2018

The moderator band (MB) is a common fibromuscular anatomical structure for the right ventricle of most animals. The histomorphometric and immunohistochemical analysis of the MBs of Egyptian Baladi cattle in relation to age was the aim of this study. Eighteen clinically healthy animals of both sexes were used for this study. The animals were divided into three groups depending on age, group I (N = 4, <1 year), group II (N = 8, 1–2 years) and group III (N = 6, 4–8 years). Cross sections of the MBs from all groups were stained with H&E, Masson's trichrome and anti‐connexin43 (Cx43) antibody for histological and immunohistochemical examinations. Also, measurements for the thickness of the endocardium of the MB as well as, the wall of its muscular artery were conducted. Bundles of Purkinje fibres (PFs) were identified peripherally in the endocardial layer and among the myocardial fibres in the core of each MB. The infiltration of endocardial adipocytes was the characteristic for MBs of old animals. All morphometric data showed a significant increase with the advancement of age. Immunohistochemical findings revealed the localization and distribution of Cx43 in the PFs and intercalated discs of all examined MBs. However, variation of Cx43 immunoreactivity was found among the groups depending on the age. On the basis of this study, this conclusion of different histomorphometry and Cx43 expression of the MBs in relation to age was drawn. These interesting findings provide further insight into age‐related physiological and pathological heart conditions.
Intrauterine infusion of human chorionic gonadotropin before embryo transfer in IVF/ET cycle: The critical review
Authors: Zhang Tao , Chen Xiaoyan , Wang Chi‐Chiu , Li Tin Chiu , Kwak‐Kim Joanne
Published: December 2018

Intrauterine infusion of human chorionic gonadotropin (IUI‐hCG) has been proposed to improve the outcome of in vitro fertilization‐embryo transfer (IVF‐ET), since it plays a critical role in synchronizing endometrial and fetal development. As the early mediator from embryo, hCG promotes the decidualization, angiogenesis, maternal immune tolerance, and trophoblast invasion, favoring successful implantation of embryo. Although multiple clinical trials have been conducted to verify the efficacy of IUI‐hCG on IVF‐ET outcome in recent years, the findings remained controversial. The difference in study design and population might be the cause to the different consequences after administration of hCG. More importantly, the endometrial receptivity, which might affect the efficacy of IUI‐hCG, has not been assessed in women receiving this intervention. Selecting the right population suitable for IUI‐hCG based on known etiology would be crucial in enhancing its efficacy and minimize any possible complications. Investigation of optimal indications for IUI‐hCG should be highlighted in the future.
GATA6 expression promoted by an active enhancer may become a molecular marker in endometriosis lesions
Authors: Izawa Masao , Taniguchi Fuminori , Harada Tasuku
Published: December 2018

Problem

Genome‐wide profiling of DNA methylation in endometriotic cells has shown a distinct facet of epigenetic backgrounds; however, specific DNA methylation sites responsible for aberrant gene expression in endometriosis were unknown. Are there specific endometriosis‐associated DNA methylations that can be used as molecular markers in endometriosis lesions?

Method of study

This study used endometriotic tissues from the chocolate cyst lining of the ovaries of patients with endometriosis, and endometrial tissues from disease‐free patients. For analysis, stromal cells were collected from endometrial and endometriotic tissues. Using endometrial cells as control, differentially methylated cytosine‐phosphate‐guanine (CpG) characteristic in endometriotic cells was extracted. Among these CpGs, we focused on a stretch of hypomethylated CpGs within GATA6 gene and examined the potential role as enhancer in endometriotic cells and tissues.

Result(s)

We identified a stretch of hypomethylated CpGs within the GATA6 gene body in endometriotic cells. Because GATA6 mRNA was highly expressed in endometriotic cells but not in endometrial cells, we then hypothesized that the hypomethylated sequence may function as an enhancer in GATA6 gene expression. Chromatin immunoprecipitation analysis predicted the presence of active enhancer within the gene body sequence in endometriotic cells. Immunohistochemistry showed a positive staining of GATA6 in ovarian chocolate cysts, while in endometrial tissues and in some peritoneal tissues with endometriosis, GATA6 staining was at a marginal level.

Conclusion

This is the first implication showing a link between an aberrant DNA methylation of cis element and gene expression in endometriosis. GATA6 expression may become a molecular marker to diagnose endometriosis lesions.