bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and tolerability of initial low-dose lenvatinib to treat differentiated thyroid cancer
Authors: Yamazaki Haruhiko , Iwasaki Hiroyuki , Takasaki Hirotaka , Suganuma Nobuyasu , Sakai Rika , Masudo Katsuhiko , Nakayama Hirotaka , Rino Yasushi , Masuda Munetaka
Published: March 2019

Some patients with differentiated thyroid cancer (DTC) may require an initial low dose (LD) of lenvatinib. However, few studies have investigated the efficacy of LD lenvatinib. We compared the efficacy and tolerability of lenvatinib at an initial LD to those of the standard initial dose of 24 mg in patients with DTC.

In this cross-sectional study, records of patients with DTC treated with lenvatinib were retrospectively reviewed. Patients were divided into 2 groups based on the initial dose of lenvatinib: a full-dose (FD) group that received an initial dose of 24 mg/d and a LD group that received an initial dose of less than 24 mg/d. Categorical variables were compared with the Fisher exact test and continuous variables with Student t test. A progression-free survival (PFS) curve was constructed with the Kaplan–Meier method. A probability (P) value of < .05 was considered statistically significant.

Thirty-six patients with DTC were treated with lenvatinib (30 in the FD group and 6 in the LD group). The response rates were 43% and 33% in the FD and LD groups, respectively. The median PFS duration was 696 [95% confidence interval (CI): 318–not available (NA)] days in the FD group. The median PFS of the LD group was not reached (95% CI: 124–NA) (P = .293). Treatment interruptions were required in 25 (83%) patients in the FD group and 4 (67%) in the LD group (P = .573). Dose reductions were required in 28 (93%) patients in the FD group and 4 (67%) in the LD group (P = .121). There were no significant differences in the incidences of common adverse events between the 2 groups.

The LD group also required dose reduction and interruption frequently. Since these findings are only the short-term results of a limited number of cases, a large number of cases and long-term observations are needed to determine whether an initial LD is effective for patients with DTC in poor general condition.
The prevalence of myopia and the factors associated with it among university students in Nanjing
Authors: Huang Luoming , Kawasaki Hiromi , Liu Yiqun , Wang Zhongliang
Published: March 2019

Myopia, a common eye disease, is a global health burden that is increasing worldwide. Although the risk factors for myopia among children have been extensively investigated, those among university students have not. The aim of our study was to investigate the prevalence of myopia and the factors associated with it among university students in Nanjing.

Subjects were selected from among the university students using a stratified random sampling method. A total of 1200 first-year university students were invited to participate in the study. A self-reported questionnaire was used to collect data on the students’ demographic information, history of parental myopia, and behavioral factors, such as having bad postures while reading or writing, performing eye exercises, taking breaks after 30 minutes of continuous reading, using computers or smartphones, sleep, near-work, and outdoor activity. Univariate analyses were performed to find the associations between myopia and the various parameters. Factors that were statistically significant in univariate analyses were selected as candidate variates for multivariate analysis.

The overall prevalence of myopia was 86.8%: 86.1% among males, and 88.0% among females (χ2 = 0.68, P = .411). Chi-squared tests showed that parental myopia, performing eye exercises, taking breaks after 30 minutes of continuous reading, and engaging in outdoor activity were significantly associated with myopia (P < .001, P = .034, P < .001, and P = .002, respectively). Having at least 1 parent with myopia was a risk factor for myopia (OR = 3.58, 95% CI = 1.96–6.54); whereas, taking breaks after 30 minutes of continuous reading and performing at least 2 hours of outdoor activity per day were protective against myopia in multivariate analysis (OR = 0.61, 95% CI = 0.41–0.93; and OR = 0.45, 95% CI = 0.2–0.99; respectively).

The prevalence of myopia among university students was 86.8%. Parental myopia was a risk factor for myopia. Taking breaks after 30 minutes of continuous reading, and engaging in at least 2 hours of outdoor activity were associated with less myopia. In addition, performing eye exercises was associated with less myopia on univariate analysis.
Malignant melanoma of the esophagus complicated with poorly differentiated mucinous adenocarcinoma of the stomach
Authors: Li Ji , Liu Yan , Wang Bin , Sun Xun , Meng Xiangwei
Published: March 2019

Rationale:

Primary malignant melanoma of the esophagus (PMME) is a rare malignancy that only accounts for <2% of all primary esophageal tumors. Here, we report the even rarer occurrence of PMME in combination with poorly differentiated mucinous adenocarcinoma of the stomach.

Patient concerns:

A 64-year-old man was presented to the hospital with >1 month of eating dysphagia. Enhanced computed tomography (CT) scan only found a space-occupying lesion in the lower esophagus with moderate enhancement. However, gastroscope showed not only esophageal masses, but also gastric mucosa changes.

Diagnoses:

Poorly differentiated mucinous adenocarcinoma and PMME were diagnosed based on pathological biopsy and immunohistochemical methods.

Interventions:

The patient underwent laparoscopic gastric cancer radical surgery, esophageal resection, and colonic replacement of the esophagus.

Outcomes:

Abdominal CT and esophagography performed 1 week after surgery showed that it was consistent with postoperative changes without other abnormalities. However, the patient died 3 months after discharge without receiving any other treatment.

Lessons:

This case suggests more attention should be drawn to the diagnosis of multiple primary malignant neoplasms in elder patients, and also highlights the need to fulfill comprehensive examinations before surgery in case of misdiagnosis. Besides, it is challenging to finding a reasonable treatment for such rare condition.
The controversy of esophageal carcinosarcoma
Authors: Xu Xiaoyang , Xu Yan , Wang Jiang , Zhao Can , Liu Chang , Wu Bin , Gao Lei , Dai Guangquan , Dai Dongqiu
Published: March 2019

Rationale:

Esophageal carcinosarcoma (ECS) is defined as a relatively rare malignant neoplasm with both epithelial carcinomatous and sarcomatous components. Besides, there were so many various controversies in ECS. This article describes a case of ECS that was effectively treated with radical esophagectomy and adjuvant chemotherapy. Also, we discuss the presentation, differential diagnosis, treatment, and prognosis of ECS.

Patient concerns:

A 58-year-old man presented with a history of progressive dysphagia and precordial pain after swallowing for 1 month.

Diagnosis:

Esophagogastroduodenoscopy (EGD) revealed a large polypoid neoplasm that occupied the esophageal lumen 30 to 34 cm from the incisors. On the characteristic morphology, clinical symptom and biopsy findings, the ECS was the primary considerated. Computed tomography (CT) examination demonstrated no radiological evidence of metastatic disease.

Interventions:

The patient underwent an Ivor Lewis esophagectomy, coupled with adequate lymph node dissection (2-field lymphadenectomy). ECS was confirmed by pathology report of postoperative. Then, the patient underwent adjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine.

Outcomes:

The patient remained alive without tumor recurrence at 24 months after multidisciplinary therapy.

Lessons:

It is generally treated by surgery, radiotherapy, and chemotherapy according to the protocols used for other esophageal cancers (EC). However, there is no recommended clinical treatment for ECS because of the rarity of the disease. Esophagectomy with extended lymphadenectomy followed by adjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine may be recommended treatment for ECS. Chemotherapy regimen with docetaxel, oxaliplatin, and capecitabine may be a suitable adjuvant therapy for ECS.
Preoperative balloon pulmonary angioplasty enabled noncardiac surgery of a patient with chronic thromboembolic pulmonary hypertension (CTEPH)
Authors: Watanabe Kenji , Ito Nobuko , Ohata Takuya , Kariya Taro , Inui Hiroshi , Yamada Yoshitsugu
Published: March 2019

Rationale:

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease with a poor prognosis, characterized by chronic thromboembolic obstruction of the pulmonary arteries and pulmonary hypertension. Balloon pulmonary angioplasty (BPA) is a newly emergent treatment for CTEPH, which may substitute pulmonary endarterectomy, the standard but more invasive treatment for CTEPH. Here, we report the case of a CTEPH patient who underwent 2 noncardiac surgeries without complications after preoperative intervention of BPA.

Patient concerns:

A 79-year-old man presented with severe osteoarthritis of bilateral knees, with adaptation of total knee arthroplasty (TKA). Transthoracic echocardiogram revealed severe pulmonary hypertension with estimated right ventricular systolic pressure of 140 mm Hg.

Diagnosis:

Pulmonary arteriography revealed total occlusion of the upper branch of the right pulmonary artery, and ventilation/perfusion scan showed multiple mismatched perfusion defects. His pulmonary artery pressure (PAP) was as high as 89/25 (46) mm Hg with normal range of pulmonary capillary wedge pressure. He was diagnosed with CTEPH.

Interventions:

Four BPA sessions for 8 branches of the bilateral pulmonary arteries were done, until the mean PAP (mPAP) went under 30 mm Hg. For the TKA, we selected spinal anesthesia in order to minimize intraoperative hemodynamic changes. Cardiac surgeons were standby in case extracorporeal membrane oxygenation (ECMO) initiation was required.

Outcomes:

With appropriate pain management and use of intravenous vasopressors, intraoperative vital signs were stable. No symptoms of hemodynamic collapse were observed postoperatively. The patient was discharged on the 46th postoperative day following rehabilitation. Two years later, left-side unicompartment knee arthroplasty (UKA) was scheduled. Right heart catheterization study revealed the mPAP was 30 mm Hg, nearly the same value as the last study. The operation was performed under spinal anesthesia with continuous arterial pressure monitoring without need for intraoperative vasopressor. He was discharged without complications on the 24th postoperative day.

Lessons:

BPA can be an effective preoperative intervention for CTEPH patients undergoing noncardiac surgery.
Comparison of the accuracy of cannulated pedicle screw versus conventional pedicle screw in the treatment of adolescent idiopathic scoliosis
Authors: Yilar Sinan
Published: March 2019

Background:

Pedicle screws are commonly used to treat adolescent idiopathic scoliosis (AIS). Many studies have discussed the rates and effects of pedicle screw misplacement. In this study, to increase the accuracy rate, cannulated pedicle screws were inserted into the periapical vertebrae, highly rotated vertebrae, and vertebrae with very thin pedicles in a single patient group. We compared these results with those of a patient group who underwent conventional pedicle screw placement.

Methods:

Twenty-eight AIS patients treated surgically between 2015 and 2017 with cannulated pedicle screws or conventional pedicle screws were included. Group 1 (n = 15) received cannulated pedicle screws, whereas group 2 (n = 13) received conventional pedicle screws. Postoperative computed tomography scans were used to evaluate pedicle screw position. Pedicle perforation was assessed using the classification by Rao et al: grade 0, no perforation; grade 1, only the threads outside the pedicle (less than 2 mm); grade 2, core screw diameter outside the pedicle (2–4 mm); and grade 3, screw entirely outside the pedicle. Medial screw malposition was measured between the medial pedicle wall and the medial margin of the screw. Lateral screw malposition was measured between the lateral corpus wall and lateral screw margin.

Results:

Placement accuracy of 703 screws (group 1, 376; group 2, 327) was evaluated. A total of 142 (20.1%) pedicle screw perforations occurred: 63 (17.1%) in group 1 and 79 (25%) in group 2 (P < .05). There was no statistically significant intergroup difference in medial perforation (group 1, 34 [9%] vs group 2, 31 [10%]). Lateral perforation was significantly less common in group 1 (n = 29; 7.7%) than in group 2 (n = 4; 14.7%) (P = .0002).

Conclusions:

The use of cannulated screws to treat AIS decreases perforation and complication rates. Although it did not significantly lower the medial perforation rate, it dramatically reduced the lateral perforation rate. The use of cannulated screws enables intraoperative confirmation of placement accuracy. Our data suggest that cannulated pedicle screw use to treat AIS is safer and more efficient.
The outcome of intervertebral surgery in the treatment of lumbar tuberculosis in children
Authors: Liang Qiang , Pu Yu , Wang Qian , Shi Jiandang , Sun Guangwei , Liu Liehua , Jin Weidong , Wang Zili
Published: March 2019

During the operation of treating lumbar tuberculosis in children, a long-segment or short-segment fixation, and fusion method were usually applied, which would adversely affect the function of normal motion unit. And so, we have been focusing on how we can shorten the range of fixation and fusion using intervertebral surgery. The objective of this retrospective study is to investigate the clinical outcome of intervertebral surgery, in the treatment of lumbar tuberculosis in children.

From June 2003 to June 2013, 18 children with lumbar tuberculosis underwent intervertebral surgery, using a combined posterior and anterior approach, in our hospital. The surgical treatments included posterior pedicle screw fixation of affected vertebrae and posterolateral bone grafting, anterior debridement, compression, and strut bone grafting. Indicators such as preoperative and postoperative erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, neurological function, visual analog scale (VAS) score, kyphotic Cobb angle, complications, healing of lesions, bone graft healing, and recurrence were statistically analyzed.

The mean follow-up time was 86.5 months (range, 62–120 months). Three months after the operation, all patients’ ESR and CRP levels decreased to normal, and both the American Spinal Injury Association neurological function scores and VAS scores improved. Successful bone graft healing was achieved, with lesions completely healed at 6 months after surgery, and no recurrence occurred. The preoperative kyphotic was 24.00° ± 13.15° (range −10°–39°), which decreased to −4.61° ± 7.31° (range −19°–10°) postoperative (Z = −4.34, P < .01); the mean deformity correction angle was 28.61° ± 8.43° (range 9°–43°). There was no significant difference between the kyphotic angle measured immediately after surgery at (−4.61° ± 7.31°) and the kyphotic angle measured at 5-year follow-up at (−3.11° ± 7.56°). The mean loss of correction was 1.50° ± 0.90°.

Intervertebral surgery using a combined posterior and anterior approach is an effective and safe method for the treatment of lumbar tuberculosis in children. It can also preserve the function of normal motor segments to the maximum extent.
Hemodialysis interval and its association with emergency care and mortality
Authors: Chien Ching-Wen , Huang Chi-Jung , Chao Zi-Hao , Huang Song-Kong , Chen Pei-En , Tung Tao-Hsin
Published: March 2019

End-stage renal disease (ESRD) incidence in Taiwan is highest worldwide. This study analyzed the relationship between health resource use and patients on hemodialysis (HD) asking for medical help as well as the outcomes in Taiwan.

This was a retrospective cohort study that analyzed the medical data of patients on dialysis, which were collected from the National Health Insurance Database of Taiwan for the period 2000 to 2010. The study sample was screened out, and new patients starting HD from 2001 to 2005 were considered.

The daily distribution of patients with ESRD in the Monday, Wednesday, and Friday (MWF) and Tuesday, Thursday, and Saturday (TTS) groups who underwent emergent HD showed remarkable person–time on Monday and Tuesday, respectively. The disease (complication) distribution in the MWF group was higher than that in the TTS group, and the statistics of heart-failure-associated diseases were significantly different. Considering 5-year survival status, the mortality rate of patients with HD was 21.94% (255 of 1162), among which those with a history of cerebrovascular disease and diabetes were 68.63% and 72.16%, respectively.

Long interdialytic intervals may induce emergency dialysis. Therefore, the frequency of emergent HD therapy has increased (thrice a week), as predicted in the current HD policy.
Treatment with Brivanib alaninate as a second-line monotherapy after Sorafenib failure in hepatocellular carcinoma
Authors: Zhu Hong , Zhang Chunyan , Yang Xi , Yi Cheng
Published: March 2019

Rationale:

Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related death worldwide. Its poor prognosis is due to the high invasiveness of the disease and limited efficacy of available treatments.

Patient concerns:

We reported an HCC patient who developed lung metastases 1 year after HCC resection. Sorafenib was then initiated; however, disease progression was noted 3 months later. Sorafenib therapy was initially maintained due to lack of effective alternatives, but disease progression continued.

Diagnoses:

HCC patient with lung metastases, and pulmonary portal, and mediastinal lymph node metastases (stage IVB).

Interventions:

Brivanib alaninate was used alone as second-line therapy.

Outcomes:

All metastases showed increased size on radiographic imaging approximately 3 months after brivanib alaninate was initiated. However, 2.5 months later, the lung metastases significantly decreased in size or disappeared. The pulmonary portal, and mediastinal lymph node metastases also significantly decreased in size. At 9.5 months after brivanib alaninate initiation, the pulmonary portal, and mediastinal lymph node metastases nearly disappeared, and the lung metastases continued to decrease in size. Alpha fetoprotein (AFP) level showed the same change pattern as the tumor-response observed on radiographic imaging. The total duration of brivanib alaninate treatment was 11 months, which was stopped due to repeated grade 2 thrombocytopenia. The other side effects were tolerable. Fifteen months after initiation of brivanib alaninate, the patient remained in very good condition without evidence of disease progression.

Lessons:

Brivanib alaninate alone as second-line therapy showed excellent antitumor efficacy for an HCC patient with numerous lung and lymph node metastases. It may exert its antitumor effects in a delayed-onset fashion. We suggest that patients receive brivanib alaninate for a long duration to fully determine its efficacy.
Significance of radiology in the diagnosis and management of ruptured left gastric artery aneurysm associated with acute pancreatitis
Authors: Valluru Bimbadhar , Yang Bin , Sharma Kalyan , Adam Ahmed Abdullahi , Wei Du , Zhou Zhou , Ali Mahamed Osman
Published: March 2019

Rationale:

Left gastric artery aneurysms are very rare which progresses into hemorrhagic shock and diagnosis is very challenging particularly in patients with acute pancreatitis and cholecystitis whose vitals become unstable suddenly.

Patient concerns:

A 72-year-old female has presented with severe progressing abdominal pain was treated with total parenteral nutrition for acute pancreatitis based on preliminary work up, but suddenly became unstable with dropping vitals over the ensuing 48 hours. Physical examination has a positive Murphy sign and appeared lethargic. She has no past history of any chronic systemic illness or malignancy.

Diagnoses:

Ruptured left gastric artery aneurysm and left hepatic artery aneurysm with intraperitoneal hemorrhage associated with acute pancreatitis and cholecystitis.

Interventions:

Emergency interventional surgery was performed to embolize both the aneurysms and the giant aneurysmal sac of the left gastric artery was secured with a micrometallic occluding coil which eventually controlled the active hemorrhage.

Outcomes:

The patient became stable and was discharged after 15 days without any recurrence or complications during the 6-month follow-up.

Lessons

This case is a peculiar example of a missed diagnosis of left gastric artery aneurysm associated with acute pancreatitis and cholecystitis with deteriorating clinical condition. Exhaustive radiological investigations are necessary for early diagnosis correlating with presenting clinical situations. Radiologists should be familiar with the challenges in diagnosis and management.
Early oral feeding versus traditional feeding after transanal endorectal pull-through procedure in Hirschsprung's disease
Authors: Ashjaei Bahar , Ghamari Khameneh Afshar , Darban Hosseini Amirkhiz Gisoo , Nazeri Niloofar
Published: March 2019

Our study questioned whether the outcome of postoperative early oral feeding is different from traditional postoperative feeding in children with Hirschsprung's disease who underwent transanal endorectal pull-through.

This was an observational and comparative study. Patients were allocated into 2 groups. Age, gender, fever, surgery-related infectious, abdominal distension, bowel obstruction, need for reoperation, peritonitis, anastomosis leak, and abscess formation were assessed. IV fluids and antibiotics usage were recorded. A Chi-square test, independent sample unpaired Student t test and Mann–Whitney test were used. P-value < .05 was considered statistically significant.

Infections occurred in no patient in group 1 and 1 patient in group 2. Stenosis occurred in 3 patients in group 1 and 2 patients in group 2. Abdominal distension occurred in 4 patients in group 1 and 3 patients in group 2. Fever occurred in 2 patients in group 1 and 1 patient in group 2 within the first 24 hours and it occurred in 13 and 17 patients, respectively, within 48 hours. All patients of group 1 (n = 15) were treated with antibiotics and intravenous fluid administration; 1 patient for 24 hours, 12 patients for 48 hours, and 1 for 72 hours, respectively. All patients of group 2 (n = 18) were treated with antibiotics and intravenous fluid administration for 5 days. We noted a significant difference regarding the duration of antibiotic treatment and intravenous fluid administration after 72 hours.

This study showed that there was no difference between the outcomes of early and traditional postoperative feeding. Due to a significant difference in the antibiotics and IV fluid administration intervals between these 2 groups which cause a prolonged hospital stay and higher costs, it seems that early postoperative feeding is superior to traditional strategy.
Estimation of nares-to-epiglottis distance for selecting an appropriate nasopharyngeal airway
Authors: Tseng Wei-Cheng , Lin Wei-Lin , Cherng Chen-Hwan
Published: March 2019

The nasopharyngeal airway is an important equipment in airway management, a correct placement is crucial for its effectiveness. We measured the nares-to-epiglottis distance (NED) and examined the correlations of the optimal insertion length (NED-1) with patient characteristics and various external facial measurements. We aimed to develop a simple method for estimating the optimal insertion length and to help select an appropriate nasopharyngeal airway.

Two hundred patients of ASA grade I & II aged >20 years undergoing elective surgery under general anesthesia were enrolled. We measured nares-to-ear tragus distance (NTD), nares-to-mandibular angle distance (NMD), philtrum-to-ear tragus distance (PTD), and philtrum-to-mandibular angle distance (PMD). The NED was measured by fiber-optic bronchoscope. All measurements were obtained in centimeters. NED-1 (cm) was defined as the optimal insertion length. The patient's sex, age, body weight, body height, and body mass index were recorded.

The NED-1 significantly correlated with body weight, body height, NTD, NMD, PTD, and PMD. Backward stepwise multiple linear regression analysis yielded the formula for predicting NED-1: 0.331 − 0.018 × BW + 0.061 × BH + 1.080 × NMD – 1.256 × PMD + 0.697 × PTD (r = 0.640, P < .001). The regression lines of the optimal insertion length versus PTD showed the best fit to the equality line. The measurements of PTD showed the minimal differences from NED-1 and with the most patients showing <1 cm differences from NED-1.

The optimal insertion depth of nasopharyngeal airway can easily be predicted by the distance from philtrum-to-ear tragus, and a nasopharyngeal airway of an appropriate size can be selected accordingly.
Comparative effectiveness of antitumour necrosis factor agents and vedolizumab in ulcerative colitis
Authors: Davis Rebecca , McParland Paula , Dodd Susanna , Storey Daniel , Probert Chris , Collins Paul , Skouras Thomas , Steel Alan , Derbyshire Edmund , Dibb Martyn , Subramanian Sreedhar
Published: March 2019

Introduction

Antitumour necrosis factor (TNF) agents and vedolizumab are used to treat ulcerative colitis (UC) but the response is variable and there is little data on comparative effectiveness. Apart from previous exposure to anti-TNF agents, predictors of response have not been identified. We aimed to (i) compare the efficacy of anti-TNF agents and vedolizumab in UC and (ii) investigate the utility of clinical and biochemical parameters in predicting response.

Patients and methods

Patients commencing any biological therapy for ambulant UC were included. Disease activity was monitored serially with the Simple Clinical Colitis Activity Index for up to 12 months. We compared the efficacy of anti-TNF agents and vedolizumab for induction and maintenance of response and remission on an intention-to-treat basis. We examined the utility of faecal calprotectin (FC) and early normalization of FC to predict response.

Results

Ninety-seven patients commencing anti-TNF and 42 commencing vedolizumab therapy were included. Vedolizumab-treated patients had significantly greater previous anti-TNF therapy exposure and a lower baseline FC. Response, remission and steroid-free remission rates were comparable between both groups at 6 weeks, 6 and 12 months. Clinical remission but not steroid-free remission at 12 months was higher in the vedolizumab group. There was a significant reduction in the Simple Clinical Colitis Activity Index and FC at 6 weeks, 6 and 12 months compared with baseline in both groups. Baseline FC and early normalization did not predict response at 6 and 12 months.

Conclusion

The efficacy of anti-TNF and vedolizumab in UC appear comparable. We could not identify any predictors of response and remission.
Bone morphogenetic protein and blood vessels: new insights into endothelial cell junction regulation
Authors: Bautch Victoria L.
Published: March 2019

Purpose of review

BMP signaling is an important regulator of vascular development and homeostasis, and perturbations of BMP pathway components are linked to vascular disease. However, until recently BMP's broad requirements in many developmental programs delayed cause-and-effect and mechanistic studies of its vascular role in vivo. This review covers recent findings that illuminate the role of BMP signaling in endothelial cells of blood vessels, and highlights effects of BMP signaling on endothelial cell junctions and vascular barrier function.

Recent findings

BMP signaling in endothelial cells of blood vessels is context-dependent, and can either be pro-angiogenic and promote vascular sprouting, or antiangiogenic and promote vascular homeostasis. I discuss how distinct BMP signaling inputs impact blood vessel formation and function, with emphasis on new studies that investigate how BMP signaling affects endothelial cell junctions and vascular permeability.

BMP signaling is important but complex in endothelial cells of blood vessels, with multiple distinct inputs leading to opposing cellular behaviors and phenotypic outputs in ways that are poorly understood. Endothelial cell–cell junctions are a target of BMP signaling, and junction stability can be tuned in either direction by BMP inputs. Several human diseases have perturbed junctions linked to BMP signaling changes.
New insights into the links between hypoxia and iron homeostasis
Authors: Renassia Cyril , Peyssonnaux Carole
Published: March 2019

Purpose of review

This review outlines recent discoveries on the crosstalk between oxygen metabolism and iron homeostasis, focusing on the role of HIF-2 (hypoxia inducible factor-2) in the regulation of iron metabolism under physiopathological conditions.

Recent findings

The importance of the hepcidin/ferroportin axis in the modulation of intestinal HIF-2 to regulate iron absorption has been recently highlighted. Latest advances also reveal a direct titration of the bone morphogenetic proteins by the erythroferrone contributing to liver hepcidin suppression to increase iron availability. Iron is recycled thanks to erythrophagocytosis of senescent erythrocytes by macrophages. Hemolysis is frequent in sickle cell anemia, leading to increased erythrophagocytosis responsible of the macrophage polarization shift. New findings assessed the effects of hemolysis on macrophage polarization in the tumor microenvironment.

Hypoxia signaling links erythropoiesis with iron homeostasis. The use of HIF stabilizing or inhibiting drugs are promising therapeutic approaches in iron-associated diseases.
CADASIL: new advances in basic science and clinical perspectives
Authors: Ferrante Elisa A. , Cudrici Cornelia D. , Boehm Manfred
Published: March 2019

Purpose of review

Recent advances in genetic evaluation improved the identification of several variants in the NOTCH3 gene causing Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Despite improved diagnosis, the disease mechanism remains an elusive target and an increasing number of scientific/clinical groups are investigating CADASIL to better understand it. The purpose of this review is to summarize the current knowledge in CADASIL.

Recent findings

CADASIL is a genotypically and phenotypically diverse condition involving multiple molecular systems affecting small blood vessels. Cerebral white matter changes observed by MRI are a key CADASIL characteristic in young adult patients often before severe symptoms and trigger NOTCH3 genetic testing. NOTCH3 mutation locations are highly variable, correlate to disease severity and consistently affect the cysteine balance within extracellular Notch3. Granular osmiophilic material deposits around blood vessels are also a unique CADASIL feature and appear to have a role in sequestering proteins that are essential for blood vessel homeostasis. As potential biomarkers and therapeutic targets are being actively investigated, neurofilament light chain can be detected in patient serum and may be a promising circulating biomarker.

CADASIL is a complex, devastating disease with unknown mechanism and no treatment options. As we increase our understanding of CADASIL, translational research bridging basic science and clinical findings needs to drive biomarker and therapeutic target discovery.
Rapamycin and treatment of venous malformations
Authors: Seront Emmanuel , Van Damme An , Boon Laurence M. , Vikkula Miikka
Published: March 2019

Purpose of review

The field of vascular anomalies has seen a fundamental change during the past 10 years. The identification of somatic genetic mutations as the explanation of sporadic vascular anomalies opened the doors to study prospectively and a posteriori the causes of various vascular malformations. This was helped by the rapidly evolving genetic techniques including the highly sensitive next generation sequencing. In parallel, knowledge on signaling alterations occurring in vascular endothelial cells because of the various mutations, development of in-vitro and especially the first in-vivo models, gave the possibility to test preclinically molecular therapies for vascular malformations.

Recent findings

One of the first molecules, rapamycin, showed clear evidence of interrupting lesion growth. As its safety profile had been established in other conditions, it was quickly accepted for clinical trials on vascular anomalies. Now, with a few trials published and others ongoing, it is establishing itself as a gold standard for molecular therapy for recalcitrant lesions.

Targeted molecular therapies are becoming interesting new additions to the management of vascular anomalies, and rapamycin is establishing itself as a gold standard for venous malformations.
Strategies for managing transfusional iron overload: conventional treatments and novel strategies
Authors: Sheth Sujit
Published: March 2019

Purpose of review

For individuals who have transfusion-dependent anemia, iron overload is the long-term complication, which results in significant morbidity. Ameliorating this is now the biggest unmet need. This review specifically addresses this issue.

Recent findings

Over the last decade or so, major advances in the treatment of these individuals, has resulted from novel strategies aimed at reducing transfusion requirement as well as optimizing chelation therapy. This review will summarize these advances and provide insights into some of the therapies in the pipeline. Strategies aimed at reducing transfusion requirement include modulation of erythropoietic regulation by reducing ineffective red cell production through activin trapping, as well as stem cell gene modification approaches, which aim for a cure, and transfusion independence. Refined means of assessing tissue iron and the introduction of oral chelators have facilitated tailoring chelation regimens with closer monitoring and improved compliance. Newer approaches to ameliorate iron toxicity have focused on the hepcidin pathway, all of which would result in increased hepcidin levels and reduction of iron absorption from the intestine, sequestration of iron in normal storage sites and reduced exposure of more susceptible organs, such as the heart and endocrine organs, to the toxic effects of increased iron.

These advances offer the promise of improved management of transfusion-dependent individuals.
Overcoming developing world challenges of cochlear implantation: Chinese perspective
Authors: van Hasselt Andrew , Sung John K.K. , Tong Michael C.F.
Published: March 2019

Purpose of review

Over a short period, China has adopted cochlear implants and emerged as a burgeoning market. This represents a valuable case study for emerging countries in terms of planning, initiating, and growing cochlear implant programs.

Recent findings

Although many challenges such as funding, establishing infrastructure, and recipient community support have been addressed, many more remain. Consistent rapid escalation in numbers has been driven by push-and-pull factors. Federal, state, and private funding have all played a role.

The review highlights the massive need for hearing rehabilitation that currently exists in China. The shortfall can only be addressed by a purposeful and coordinated approach involving government policy, The China Disabled Persons Federation, the industry partnering with hearing and medical professionals and the deaf community.
Langerhans Cell Histiocytosis With Vertebral Involvement Diagnosed and Treated Over the Last 15 Years in a Single Canadian Pediatric Academic Institution
Authors: Gatineau-Sailliant Sophie , Grimard Pascale , Miron Marie-Claude , Grimard Guy , Carret Anne-Sophie , Leclerc Jean-Marie
Published: March 2019

We report 11 children with vertebral lesion of Langerhans cell histiocytosis (LCH) diagnosed and treated between 2000 and 2015. Vertebral lesions were usually present at LCH diagnosis. No child developed neurologic symptoms. Among 29 vertebral lesions, only 2 were unstable. Chemotherapy was used in all children but 3. A LCH recurrence was observed in 6 patients, involving vertebrae in 4 cases. All children were disease-free at their last follow-up. Sequelae were more often radiologic than clinical. Since potential recurrences and incomplete bone regeneration exist, discussion about optimal treatment and long-term follow-up of vertebral lesions are essential.
Paternal Preferences, Perspectives, and Involvement in Perinatal Decision Making
Authors: Cheng Erika R. , McGough Haley , Tucker Edmonds Brownsyne
Published: March 2019

Importance

Despite increasing attention to the importance of father involvement during pregnancy, the literature on fathers' roles in perinatal decision making is scant.

Objective

The aim of this study was to conduct a narrative review of the literature exploring fathers' preferences, perspectives, and involvement in perinatal decision making.

Evidence Acquisition

We searched PubMed, Ovid, EMBASE, Cochrane Library, and CINAHL databases using the terms father, spouse(s), husband, and paternal separately with the combined terms of attitude, preference, involvement, influence, informed consent, decision making, pregnancy, labor induction, genetic testing, prenatal diagnosis, amniocentesis, fetal surgery, genetic abnormalities, congenital anomalies, birth defects, perinatal, and antenatal. The search was limited to English-language studies that were published anytime and conducted between July and September 2018.

Results

The initial search identified 616 articles; 13 articles met criteria for inclusion. Fathers view themselves as serving distinct roles in perinatal decision making and have specific informational needs that would support their involvement in decision making. Although fathers want to support their partners and learn about fetal health, they often feel excluded from perinatal screening decisions. Mothers and fathers also have different needs, concerns, and preferences regarding key perinatal decisions that, if unresolved, can impact the couples' relationship and perinatal outcomes.

Conclusions

Findings provide import insights into the distinct experiences, roles, needs, and perspectives of fathers facing perinatal decision making.

Relevance

Advancing research and policy on fathers' involvement in perinatal decision making could lead to a paradigm shift in how maternity care is structured, how obstetric services are delivered, and how perinatal interventions are designed and implemented.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to describe why fathers are important to perinatal health; assess gaps in care practices that limit father involvement in perinatal decision making; evaluate situations where fathers wish to be involved in perinatal decision making; and list opportunities for future research in this area.
Too Many Women Are Dying From Cervix Cancer: Problems and Solutions
Authors: Gaffney David K. , Hashibe Mia , Kepka Deanna , Maurer Kathryn A. , Werner Theresa L.
Published: March 2019

(Abstracted from Gynecol Oncol 2018;151:547–554)

Nearly all cases of cervical cancer are due to infection with the human papillomavirus (HPV) virus. Globally, more than 270,000 women per year die of this cancer.
The Management of Nausea and Vomiting of Pregnancy: Synthesis of National Guidelines
Authors: Tsakiridis Ioannis , Mamopoulos Apostolos , Athanasiadis Apostolos , Dagklis Themistoklis
Published: March 2019

Importance

Nausea and vomiting of pregnancy (NVP) affects a high proportion of the pregnant population.

Objective

The aim of this study was to compare and synthesize recommendations from national guidelines regarding the management of NVP.

Evidence Acquisition

A descriptive review of 3 recently published national guidelines on NVP was conducted: Royal College of Obstetricians and Gynaecologists on “The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum,” American College of Obstetricians and Gynecologists on “Nausea and Vomiting of Pregnancy,” and Society of Obstetricians and Gynaecologists of Canada on “The Management of Nausea and Vomiting of Pregnancy.” These guidelines were summarized and compared in terms of the recommended management of pregnant women. The quality of evidence was also reviewed based on the method of reporting.

Results

Several differences were identified on the different guidelines regarding the management of NVP. Frequent small meals and avoidance of iron supplements are recommended for prevention. The consumption of ginger, acustimulations, antihistamines, phenothiazines, dopamine, and serotonin 5-hydroxytryptamine type 3 receptor antagonists is routinely recommended for use in the community as treatment.

Conclusions

Evidence-based medicine may lead to the adoption of an international guideline for the management of NVP, which may lead to a more effective management of that entity.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After participating in this activity, the learner should be better able to synthesize management recommendations in cases of NVP; assess the preventive and nonpharmacologic regimens in cases of NVP; and propose the necessary pharmacologic treatment in cases of NVP.
Effects of Exercise During Pregnancy in Women With Short Cervix: Secondary Analysis From the Italian Pessary Trial in Singletons
Authors: Saccone Gabriele , Berghella Vincenzo , Venturella Roberta , D'Alessandro Pietro , Arduino Bruno , Raffone Antonio , Giudicepietro Antonia , Visentin Silvia , Vitagliano Amerigo , Martinelli Pasquale , Zullo Fulvio
Published: March 2019

(Abstracted from Eur J Obstet Gynecol Reprod Biol 2018;229:132–136)

Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Over the last few years, cervical assessment has moved from digital examination to ultrasound evaluation, and ultrasound of the cervix has been the focus of much research.
The overview of the Australian trauma system
Authors: Warren Kirrily-Rae J. , Morrey Chris , Oppy Andrew , Pirpiris Marinis , Balogh Zsolt J.
Published: March 2019

Trauma management in Australia is predominantly that of blunt mechanism trauma spread across a geographically large and sparsely populated country. A complex network of patient care has evolved to manage major trauma. Over recent decades, focus has been given to improving and co-ordinating transfer of patients into major trauma centers and improved data collection with the corresponding improved patient outcomes. This article provides an overview of the nature and structure of the Australian trauma system and its regulation.
Late Occurrence of Raccoon Eyes
Authors: Bogdanović Milenko , Popović Vesna , Savić Slobodan , Durmić Tijana , Radnić Bojana
Published: March 2019

This case represents a planned complex suicide in which the victim combined gunshot to the head and hanging. The most interesting finding in the presented case was pale face, but without any visible injury to it at the time the body was found (more than 24 hours after death), whereas at autopsy (20 hours later), black eyes were prominent. The removal of the ligature led to the decompression of the neck and its blood vessels with consequential blood redistribution, which, alongside the liquid state of blood, resulted in the aforementioned finding. Considering the described postponed appearance of periorbital ecchymosis, this kind of finding suggests that great caution is necessary when interpreting hematomas in terms of their vitality.
Interobserver Agreement for Mismatch Repair Protein Immunohistochemistry in Endometrial and Nonserous, Nonmucinous Ovarian Carcinomas
Authors: Sari Aysegul , Pollett Aaron , Eiriksson Lua R. , Lumsden-Johanson Brenda , Van de Laar Emily , Kazerouni Hamid , Salehi Amir , Sur Monalisa , Lytwyn Alice , Ferguson Sarah E.
Published: March 2019

Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is an established test to identify Lynch syndrome (LS) in patients with colorectal cancer and is being increasingly used to identify LS in women with endometrial and/or nonserous ovarian cancer (OC). We assessed interobserver agreement in the interpretation of MMR-IHC on endometrial and ovarian carcinomas. The study consisted of 73 consecutive endometrial cancers (n=48) and nonserous, nonmucinous epithelial OCs (n=25). Six pathologists from 2 cancer centers, one with and the other without, previous experience in interpreting MMR-IHC, evaluated MLH1, MSH2, MSH6, and PMS2 stains. Before the study, an experienced pathologist led a review of 9 teaching cases. A decision tool was developed as a guide in MMR-IHC interpretation. Staining was interpreted as intact, deficient, or equivocal for each protein. Interobserver agreement for the patient MMR status was categorized as “almost perfect” with κ=0.919 (95% CI, 0.863-0.976). All observers were in agreement in 66 (92%) tumors. Four of the less experienced pathologists had at least 1 discrepant interpretation. There were 6 discordant cases: 3 MMR-deficient cases and 2 MMR-intact cases by majority opinion were called equivocal by at least 1 observer, and 1 MMR-deficient case by majority opinion was interpreted as MMR intact by 1 pathologist. Only the latter case (1/73 patients, 1.4%) had an unequivocal disagreement that could affect patient management. Issues associated with discordant interpretation included heterogeneous staining, intratumoral lymphocytes, regional reduced internal control tissue staining, and scattered absent/weak staining adjacent to tumor cells with strong nuclear staining.
Congenital Adrenal Hyperplasia—When Clinical Symptoms Are Missing
Authors: Ferraz Liz Catarina , Rocha Alberto
Published: March 2019

Background

Congenital adrenal hyperplasia is an autossomic recessive condition. The most common mutation is in the CYP21A2 gene situated in chromosome 6, leading to a 21-hydroxylase deficiency. Clinical presentation ranges from light hyperandrogenism to potentially fatal adrenal salt-losing crisis. In this study, we describe a case of congenital adrenal hyperplasia in a male newborn.

Case

A male newborn was brought to the emergency department owing to an episode of regurgitation after feeding, followed by pallor of the skin and decreased activity. In physical examination, he was hypotonic with irregular respiratory pattern. Heart rate was 180 beats per minute, blood pressure levels were 93/63 mm Hg, and peripheral oxygen saturation was 80% to 84% associated with a sine wave pattern in the electrocardiogram. No scrotal hyperpigmentation was present. The venous blood gas analysis showed a metabolic acidosis (pH, 7.28; pCO2, 41 mmHg; sodium bicarbonate, 18.2 mmol/L; and base excess of −7), hyperkalemia (9.3 mmol/L), and hyponatremia (112 mmol/L). Based on these findings, the most probable diagnosis was a salt wasting form of congenital adrenal hyperplasia. Treatment of hyperkalemia and sodium deficit correction were initiated, as well as glycorticoid therapy. The concentration of 17-hydroxyprogesterone in dried blood spot confirmed the diagnosis.

Conclusions

Because of the severity of this disease and the risk for rapid hemodynamical collapse, clinicians should be aware of this condition. In this specific case, we highlight the absence of testicular hyperpigmentation, which is a hallmark of this condition.