bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of OTX-101, a Novel Nanomicellar Formulation of Cyclosporine A, on Corneal Staining in Patients With Keratoconjunctivitis Sicca: A Pooled Analysis of Phase 2b/3 and Phase 3 Studies
Authors: Malhotra Ranjan , Devries Douglas K. , Luchs Jodi , Kabat Alan , Schechter Barry A. , Shen Lee Bridgitte , Shettle Lee , Smyth-Medina Robert , Ogundele Abayomi , Darby Charles , Bacharach Jason , Karpecki Paul
Published: July 2019

Background:

Keratoconjunctivitis sicca affects 5% to 33% of the population and is often accompanied by symptoms such as burning and dryness. This pooled analysis evaluated total and central corneal fluorescein staining (CFS) in patients receiving OTX-101 0.09% or vehicle in phase 2b/3 and 3 studies and whether improvements in corneal staining correlated with improved visual acuity.

Methods:

In these randomized, vehicle-controlled studies, patients received 1 drop of OTX-101 or vehicle in both eyes twice daily. Corneal staining was performed at baseline and days 28, 56, and 84. CFS was evaluated in each zone (0-to-4 scale); total corneal staining (0-to-20 scale per eye) was averaged over both eyes. Pooled safety assessments included adverse event monitoring.

Results:

Mean baseline CFS total scores (SD) were 4.2 (2.5) and 4.3 (2.6) for the OTX-101 (n = 523) and vehicle (n = 525) groups, respectively. For total corneal staining, least squares mean changes from baseline (standard error) were −0.9 (0.08) versus −0.5 (0.08) for OTX-101 and vehicle, respectively (P = 0.0008), on day 28 and −1.4 (0.09) versus −0.9 (0.09) on day 84 (P = 0.0002). There was a significantly high correlation (P = 0.0117) between reduced central corneal staining and improved visual acuity on day 84. Treatment-related adverse events were mostly mild, with instillation site pain reported by 21.8% and 4.0% of patients receiving OTX-101 and vehicle, respectively.

Conclusions:

Treatment with OTX-101 led to greater improvements versus vehicle in corneal surface staining as early as 4 weeks, and further improvements were seen up to 12 weeks. OTX-101 was well tolerated in patients with keratoconjunctivitis sicca.
Synergy Testing of Antiamoebic Agents for Acanthamoeba: Antagonistic Effect of Voriconazole
Authors: Talbott Maya , Cevallos Vicky , Chen Michael C. , Chin Stephanie A. , Lalitha Prajna , Seitzman Gerami D. , Lietman Thomas M. , Keenan Jeremy D.
Published: July 2019

Purpose:

To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro.

Methods:

Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole. The minimum cysticidal concentration (MCC) for each drug pair was estimated for each isolate, and the summed fractional cysticidal concentration (ΣFCC) was calculated for each drug combination in the checkerboard, with synergy defined as a lack of growth at a ΣFCC ≤ 0.5 and antagonism as growth at a ΣFCC > 4.

Results:

Chlorhexidine and propamidine were cysticidal, with median MCCs of 12.5 (range 1.5–50) and 11.7 (range 0.2–250), respectively. Voriconazole was not cysticidal, with a median MCC of >10,000 μg/mL. The combination of chlorhexidine and propamidine did not markedly change the cysticidal activity compared with either drug alone. By contrast, voriconazole antagonized the cysticidal activity of both chlorhexidine and propamidine, with Acanthamoeba growth observed at antagonistic ΣFCCs in 27 of 49 (55.1%, 95% confidence interval 35.7%–78.6%) checkerboard combinations of voriconazole and chlorhexidine and in 58 of 147 (39.5%, 95% confidence interval 14.3%–50.3%) combinations of voriconazole and propamidine.

Conclusions:

In an in vitro assay, voriconazole reduced the cysticidal activity of 2 commonly used antiamoebic drugs. Although the in vivo drug interactions could be different, these observations may be useful in cases of nonhealing Acanthamoeba keratitis being treated with combination therapies that include voriconazole.
Corneal Subbasal Nerve Analysis Using In Vivo Confocal Microscopy in Patients With Dry Eye: Analysis and Clinical Correlations
Authors: Liu Yan , Chou Yilin , Dong Xuran , Liu Ziyuan , Jiang Xiaodan , Hao Ran , Li Xuemin
Published: July 2019

Purpose:

This study aimed to observe corneal subbasal nerves and Langerhans cells (LCs) using in vivo confocal microscopy (IVCM) in patients with dry eye, a tool for the evaluation of disease stage and severity and for treatment monitoring at the microstructural level.

Methods:

A total of 107 eyes from 62 patients were included. The Ocular Surface Disease Index (OSDI) questionnaire and other examinations were used to assess dry eye symptoms and signs. IVCM was performed to observe subbasal corneal nerves and LCs. Corneal nerves were graded using both objective and subjective methods. The correlations between dry eye symptoms and corneal nerve parameters, corneal nerve grading, and LC number were analyzed.

Results:

Corneal nerve length was negatively correlated with sensitivity to light [correlation coefficient (CC)= −0.24, P < 0.05]; nerve width was positively correlated with the OSDI score, painful eyes, and blurred vision (CC = 0.41, 0.23, and 0.46, respectively, all P < 0.05); and nerve tortuosity was positively correlated with sensitivity to light (CC = 0.23, P < 0.05). Moreover, both total objective and subjective grading scores were positively correlated with OSDI scores (CC = 0.48 and 0.27, respectively, both P < 0.05). LC number was found not to be significantly correlated with dry eye symptoms (P > 0.05).

Conclusions:

IVCM is a useful tool to evaluate corneal subbasal nerve changes in patients with dry eye. Detailed nerve grading could help to understand and evaluate the pathophysiologic conditions of the disease and could be used for further treatment follow-up in the future.
Limbal and Conjunctival Epithelial Thickness in Ocular Graft-Versus-Host Disease
Authors: Kheirkhah Ahmad , Coco Giulia , Satitpitakul Vannarut , Pham Tommy T. , Dana Reza
Published: July 2019

Purpose:

To compare the thickness of the limbal epithelium (LE) and the bulbar conjunctival epithelium (BCE) between patients with dry eye disease (DED) with and without ocular graft-versus-host disease (GVHD).

Methods:

This cross-sectional study enrolled 40 patients with moderate to severe DED including 20 with and 20 without chronic ocular GVHD. All patients had a comprehensive clinical ophthalmic assessment. Moreover, the thickness of the LE and BCE in both nasal and temporal regions of both eyes was measured using spectral domain optical coherence tomography.

Results:

The average LE thickness in all patients with dry eye (GVHD and non-GVHD) was 65.8 ± 11.9 μm temporally and 69.7 ± 11.1 μm nasally (P = 0.02). The average BCE thickness was 55.8 ± 11.4 μm temporally and 60.1 ± 11.0 μm nasally (P = 0.03). There were no statistically significant differences between GVHD and non-GVHD groups in LE thickness (69.6 ± 11.7 vs. 66.1 ± 6.2 μm, respectively, P = 0.31) or BCE thickness (58.9 ± 9.6 vs. 57.3 ± 9.8 μm, respectively, P = 0.82). There was a significant correlation between LE thickness and BCE thickness (P = 0.01, Rs = 0.41). A statistically significant negative correlation was also observed between LE thickness and age (P = 0.002, Rs = −0.35). There were no significant correlations between the thickness of the LE or BCE and other clinical parameters.

Conclusions:

No difference exists in the thickness of the ocular surface epithelia between dry eyes with and without ocular GVHD, which would suggest that these epithelial changes may be independent of the underlying etiology and possibly only reflect the disease severity. Furthermore, there are regional variations in the thickness of the ocular surface epithelia in patients with DED.
Carvedilol Combined With Ivabradine Improves Left Ventricular Diastolic Dysfunction, Clinical Progression, and Survival in Cirrhosis
Authors: Premkumar Madhumita , Rangegowda Devaraja , Vyas Tanmay , Khumuckham Jelen S. , Shasthry Saggere M. , Thomas Sherin S. , Goyal Ritu , Kumar Guresh , Sarin Shiv K.
Published: July 2019

Background:

Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis.

Patients and Methods:

THR was defined as heart rate reduction to 55 to 65 beats per minute. Of 260 patients with cirrhosis, 189 (72%) with LVDD were randomized to THR [group (Gr.)A; n=94; carvedilol±ivabradine)] or standard care (Gr.B; n=95; no β-blockers) and followed for 12 months.

Results:

In Gr.A, THR was achieved at 4 weeks in 88 (93%) patients (responders, R): 48 (61.5%) with carvedilol alone and 40 (86.9%) of 46 patients with additional ivabradine. In Gr.A, LVDD reversed in 16 (20.5%) and improved from grade 2 to 1 in 34 (35.4%)], whereas in Gr.B, it progressed from grade 1 to 2 in 10 (10.5%) patients. At 12 months, 21 (11.1%) patients died, 6 (14%) in Gr.A and 15 (18%) in Gr.B (P=0.240), but no mortality was seen in those who had persistent THR at 1 year (n=78; P=0.000). In multivariate analysis, model for end-stage liver disease [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.22-2.75; P=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28; 95% CI, 1.23-2.42; P=0.048) predicted 1-year mortality. Nonresponders had an increased mortality risk (HR, 1.3; 95% CI, 1.2-1.8; P=0.046) independent of age, gender, and baseline model for end-stage liver disease. Levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone were reduced (P<0.01) in responders. More patients in Gr.B developed acute kidney injury (odds ratio, 4.2; 95% CI, 2.8-10.5; P=0.027) and encephalopathy (odds ratio, 6.6; 95% CI, 1.9-9.7; P=0.040).

Conclusions:

Ivabradine combined with carvedilol improves LVDD, achieves THR more often and reduces risk of encephalopathy, acute kidney injury with improved survival in patients with cirrhosis.
A Role for Alveolar Exhaled Nitric Oxide Measurement in the Diagnosis of Hepatopulmonary Syndrome
Authors: Lam Shin Cheung Jeffrey , Naimi Madina , Sykes Jenna , Gupta Samir
Published: July 2019

Goals:

The authors sought to characterize predominantly alveolar exhaled nitric oxide (eNO) in hepatopulmonary syndrome (HPS) compared with non-HPS, changes after liver transplantation, and diagnostic properties.

Background:

HPS is defined by liver disease, intrapulmonary vascular dilatations (IPVDs), and hypoxemia. Rat models and small human studies suggest that NO overproduction may cause IPVDs.

Study:

A retrospective review of the Canadian HPS Database (2007 to 2017) and prospective eNO measurement (main outcome) in healthy controls (measurement expiratory flow, 200 mL/s). HPS was defined as: (1) liver disease; (2) contrast echocardiography consistent with IPVDs; and (3) partial pressure of arterial oxygen <70 mm Hg with alveolar-arterial gradient >20 mm Hg; subclinical HPS as criteria (1) and (2) only; and no HPS as criterion (1) only. Current smokers and subjects with asthma or pulmonary hypertension were excluded. A linear mixed effects model was used to compare eNO between groups and before and after transplantation.

Results:

eNO was 10.4±0.7 ppb in HPS (n=26); 8.3±0.6 ppb in subclinical HPS (n=38); 7.1±1.0 ppb in no HPS (n=15); and 5.6±0.7 ppb in controls (n=30) (P<0.001). eNO decreased from 10.9±0.8 ppb preliver to 6.3±0.8 ppb postliver transplant (n=6 HPS, 6 subclinical HPS) (P<0.001). eNO <6 ppb was 84.4% (73.1% to 92.2%) sensitive and ≥12 ppb was 78.1% (69.4% to 85.3%) specific for HPS (vs. subclinical HPS).

Conclusions:

HPS subjects have higher alveolar eNO than non-HPS subjects, levels normalize with liver transplantation. Applying eNO cutoff values may aid in HPS diagnosis.
Diagnostic and prognostic role of HE4 expression in multiple carcinomas
Authors: Kumarasamy Chellan , Madhav Madurantakam Royam , Sabarimurugan Shanthi , Lakhotiya Kartik , Pandey Venkatesh , Priyadharshini T , Baxi Siddhratha , Gothandam KM , Jayaraj Rama
Published: July 2019

Background:

Human epididymis protein 4 (HE4) protein has garnered a great degree of interest as a complementary biomarker to carbohydrate antigen 125 (CA125), or even as an independent biomarker for monitoring, diagnosis, and prognostication of ovarian cancer. Its use is currently limited to ovarian cancer. Recent studies have suggested that it could also be used in other types of cancers.

Methods:

The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines was used to design this meta-analysis protocol. The final study will also be conducted under the PRISMA guidelines for systematic reviews and meta-analyses. The core bibliographic database search will be carried out by 2 reviewers working individually, with each conducting an initial screening based on titles and abstracts. The shortlisted articles will be selected for review and statistical analysis based on predefined inclusion and exclusion criteria. Study characteristics, relevant clinicopathological characteristics and statistical data required for meta-analysis (hazard ratios [HRs] and 95% confidence interval [CIs) will be extracted and compiled into a MS Excel datasheet. Meta-analysis will be performed, using a random-effects model, and the results (pooled HR and 95% CI) will be presented in the form of a forest plot. Publication bias will also be assessed by use of Egger bias indicator test and funnel plot symmetry. If data are insufficient, a narrative line of review will be pursued.

Discussion:

HE4 protein has been shown to have great potential for clinical use as a diagnostic and prognostic marker in epithelial ovarian cancer (EOC). However, HE4 is not only limited to expression in ovarian cancer, but is also overexpressed in lung and endometrial cancers. The effectiveness of HE4 as a biomarker in cancers (other than EOC) has not yet been studied in the form of a comprehensive systematic review and meta-analysis. The results of this study should allow for expanded use of HE4 as a multiutility biomarker in multiple cancer types, thereby, elevating HE4's value as a cancer biomarker.

PROSPERO registration:

CRD42019120326.
Uniport video assisted thoracoscopic surgery (U-VATS) exhibits increased feasibility, non-inferior tolerance, and equal efficiency compared with multiport VATS and open thoracotomy in the elderly non-small cell lung cancer patients at early stage
Authors: Zhao Ruixing , Shi Zhihua , Cheng Siqiang
Published: July 2019

This study aimed to compare the feasibility, efficacy and safety among uniport video assisted thoracoscopic surgery (U-VATS), multiport VATS (M-TATS), and open thoracotomy in elderly non-small cell lung cancer (NSCLC) patients at early stage.

One hundred ninety-one elderly NSCLC patients at early stage underwent U-VATS (N = 73), M-VATS (N = 56) or open thoracotomy (N = 62) were included. Perioperative parameters, short-term outcomes, postoperative complications, and overall survival (OS) were assessed.

Three-group analysis disclosed that operational duration, blood loss, drainage duration, hospital stay, pain score on the first day (D1) and D3, patients’ global assessment (PGA), lasing air leak, infection, arrhythmia, and cardio-cerebrovascular events incidences were different among U-VATS, M-VATS, and open thoracotomy groups. Subsequently, 2-group analysis revealed that:

In addition, there was no difference of OS among 3 groups, nor between any of the 2 groups.

U-VATS presents with elevated feasibility, non-inferior tolerance, and similar efficacy compared with M-VATS and open thoracotomy in the elderly NSCLC patients at early stage.
The efficacy of fascia iliaca compartment block for pain control after hip fracture
Authors: Hong Hui-kan , Ma Yi
Published: July 2019

Background:

To assess the effect of fascia iliaca compartment block (FICB) on pain control and morphine consumption in patients with hip fracture.

Methods:

We searched databases (PubMed, Embase, Cochrane Library) for eligible randomized controlled trials (RCTs) published prior to September 12, 2018. We only included hip fracture patients who received FICB versus placebo for pain control. Risk ratios (RRs), standard mean differences (SMD) and 95% confidence intervals (CI) were determined. Stata 12.0 was used for the meta-analysis.

Results:

Eleven trials involving 937 patients underwent hip fracture were retrieved. FICB significantly decreased the pain intensity at 1–8 h (SMD = −1.03, 95% CI [−1.48, −0.58],P= .000), 12 h (SMD = −1.06, 95% CI [−1.36, −0.75],P= .000), 24 h (SMD = −1.14, 95% CI [−1.66, −0.62],P= .000) and 48 h (SMD = −0.96, 95% CI [−1.33, −0.60],P= .000). Moreover, FICB could reduced the total morphine consumption and the occurrence of nausea (P< .05). There was no significant difference between the pain intensity at 72 h (SMD = 0.11, 95% CI [−0.12, 0.34],P= .355).

Conclusions:

FICB has a beneficial role in reducing pain intensity and morphine consumption after hip fracture. Moreover, FICB has morphine-sparing effects when compared with a control group. More high-quality RCTs are needed to identify the optimal technique and volume of injectate for FICB.
HCV compliance and treatment success rates are higher with DAAs in structured HCV clinics compared to general hepatology clinics
Authors: Chehl Navdeep , Maheshwari Anurag , Yoo Hwan , Cook Colleen , Zhang Talan , Brown Sara , Thuluvath Paul J.
Published: July 2019

The real-world cure rates for hepatitis C (HCV) with direct-acting antivirals (DAAs) based on intention-to-treat (ITT) analysis may be lower than reported in the literature because of non-compliance.

To determine whether patients treated in a structured outpatient HCV clinic (SHC) had higher compliance and treatment success rates compared to those treated in general hepatology clinics (GHC).

In this study, we compared the treatment and compliance success rates of 488 and 840 patients treated in the SHC and GHC, respectively. The SHC required a pre-treatment clinic visit when patients picked up their initial medication, and received detailed education of the treatment plan and follow-up. In the GHC, the medications were delivered to patients’ homes, and there was less formal education. Compliance success was defined as a combination of treatment completion and obtaining at least 1 post-treatment viral load at week 4 or 12. Treatment success was defined as either SVR4 or SVR12.

Fifty of 488 (10.3%) patients from the SHC and 163 of 840 (19.4%) patients from the GHC were lost to follow-up (P < .0001). sustained virological response (SVR) rates were similar in compliant patients in both the SHC (419/438, 95.6%) and GHC (642/677, 94.8%), but treatment success rates by intention to treat (ITT) (overall 79.9%) were higher in SHC compared to GHC (85.9% vs 76.4%, P < .0001). Multivariate analysis showed that female patients (P = .01), older age (P = .0005), treatment in SHC (OR 1.7, 95% CI 1.2, 2.3, P = .0008), and sofosbuvir/simeprevir compared to sofosbuvir/ledipasvir had higher odds of compliance success; elbasvir/grazoprevir or dasabuvir/ombitasvir/paritaprevir/ritonavir had lower odds of compliance success compared to sofosbuvir/ledipasvir. Female patients (P = .02), older age (P < .0001), previous treatment (P = .03), treatment in SHC (OR 1.7, 95% CI 1.2, 2.3, P = .0008), and sofosbuvir/ledipasvir compared to sofosbuvir/velpatasvir, sofosbuvir, or elbasvir/grazoprevir had higher odds of treatment success. With 1:1 matching, the SHC group still had significantly higher odds than the GHC group of achieving treatment and compliance success.

Our study shows that the effectiveness of HCV treatment could be improved by coordinating treatment in a structured HCV clinic.
Fetal carotid-jugular fistula
Authors: Hu Jia , Zeng Xi , Yuan XinChun
Published: July 2019

Rationale:

Fetal carotid-jugular fistula is an extremely rare clinical entity that presents as an abnormal passage between the carotid artery and the jugular vein. It is difficult to treat and the chance for a cure is very low. The fetal carotid-jugular fistula causes congestive heart failure and death of the fetus.

Patient concerns:

We report a case of fetal carotid-jugular fistula diagnosed at 27 weeks of pregnancy. She had no history of viral infection, no history of toxic and radiation exposure, no trauma during pregnancy, and no known family history of malformations or genetic disease.

Diagnoses:

Ultrasound revealed fetal left carotid-jugular fistula formation, massive reflux in the fetal tricuspid, a large amount of fetal pericardial effusion, fetal left ear microtia and full heart enlargement.

Interventions:

The pregnant patient experienced termination of the pregnancy at 27 weeks.

Outcomes:

There were no complications in the patient. Post-termination, diagnosis of carotid-jugular fistula and left ear microtia was confirmed in the fetus.

Lessons:

Our case indicated that the congenital neck artery and venous fistula of the fetus are extremely rare, and its most serious clinical symptom is congestive heart failure leading to intrauterine cessation of pregnancy. In addition, it is difficult to treat and the chance for a cure is very low. At present, there is no treatment record related to the fetal carotid artery and venous fistula, so it is very important to make a correct diagnosis as early as possible for the health of pregnant women.
Effect of urinary sodium-to-potassium ratio change on blood pressure in participants of the longitudinal health of adults study - ELSA-Brasil
Authors: Pereira Taísa Sabrina Silva , Mill José Geraldo , Griep Rosane Harter , Sichieri Rosely , Molina Maria del Carmen Bisi
Published: July 2019

To assess the effect of changing the sodium to potassium (Na/K) ratio on blood pressure at 4 years of follow-up.

The measurements were carried out under identical conditions in two study periods (2008–2010 and 2012–2014). Urinary excretion of sodium and potassium (mmol/L) over 12 nocturnal hours was used to calculate the Na/K ratio and categorized by quintile. The 24-hour sodium and potassium intake was estimated using a validated equation. The mean BP was calculated from 3 measurements after 5 minutes of rest. Of the 15,105 participants at baseline, 14,014 completed the first follow-up. Participants without validated urine collection (n = 5,041), using antihypertensive medication (n = 3,860) at either time points or reporting bariatric surgery during follow-up (n = 45) were excluded. The differences between follow-up and baseline values were calculated for BP and the Na/K ratio. Analyses were stratified by sex and adjusted for confounding variables.

Sodium intake did not change from baseline, but potassium intake increased by approximately 150 mg in both sexes (P < .001), with a consequent reduction of the Na/K ratio. The highest quintile of change in the Na/K ratio was associated with greater variation in BP. When adjusted for covariates, it is possible to observe an increase in SBP in women from the third quintile of the Na/K ratio, in men this increase was observed from the fourth quintile. However, for DBP this increase is observed from the third quintile in both men and women.

Increase in SBP was observed in women from the third quintile of the Na/K ratio, in men this increase is observed from the fourth quintile. However, for DBP this increase is observed from the third quintile in both men and women. The Na/K ratio demonstrated a greater association in BP.
Prognostic impact of leukocytosis in intracerebral hemorrhage
Authors: Yu Zhiyuan , Zheng Jun , Guo Rui , Ma Lu , You Chao , Li Hao
Published: July 2019

Background:

Intracerebral hemorrhage (ICH) is correlated with high rate of death and poor outcome. Leukocytes participate in secondary brain injury in ICH. It is still not clear that whether leukocytosis can predict outcome in ICH. This study was performed to summarize that current evidences about the association between baseline leukocytosis and outcome in ICH patients in a systematic review and meta-analysis.

Methods:

Published studies were searched in 5 databases. Original studies about association between baseline leukocytosis and outcome in ICH were included. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were achieved to evaluate the association between leukocytosis and prognosis.

Results:

A total of 19 eligible studies with 6417 patients were analyzed in this study. Meta-analysis showed baseline leukocyte count increase was significantly associated with worse overall (OR = 1.13, 95% CI 1.05–1.21, P = .001), short-term (OR = 1.20, 95% CI 1.05–1.38, P = .009), and long-term functional outcome (OR = 1.12, 95% CI 1.04–1.20, P = .004). Baseline leukocytosis defined by cut-off values had significant association with worse overall functional outcome (OR = 1.95, 95% CI 1.01–3.76, P = .046). Baseline leukocyte count increase was significantly associated with higher overall (OR = 1.10, 95% CI 1.02–1.18, P = .011) and long-term mortality (OR = 1.12, 95% CI 1.03–1.22, P = .007). Baseline leukocytosis defined by cut-off values was significantly associated with higher overall (OR = 1.67, 95% CI 1.23–2.27, P = .001) and short-term mortality (OR = 1.74, 95% CI 1.12–2.70, P = .014).

Conclusion:

Baseline leukocytosis could be helpful in predicting prognosis in ICH patients. However, its prognostic value should be verified by further studies.
Blood pressure variability with different measurement methods
Authors: Del Giorno Rosaria , Balestra Lorenzo , Heiniger Pascal Simon , Gabutti Luca
Published: July 2019

Blood pressure variability (BPV) is an independent cardiovascular risk factor in hypertensive patients. The best method for quantifying BPV is still an object of debate. The existence of different BPV patterns, particularly age and arterial stiffness related, is postulated. Our aims were:

Cross-sectional study in 108 elderly hypertensive hospitalized patients. Each patient underwent blood pressure measurements with 5 different modalities: 24 hour BP and pulse wave velocity (PWV) monitoring (24hBPM), measurement by nurses or physicians, self-measurement and beat-to-beat monitoring. Differences between maximum and minimum values (ΔBP), averages of the absolute differences between consecutive values (ARV) and coefficients of variation (CV) were calculated.

ΔBP showed the wider values’ dispersion (Δ systolic blood pressure (SBP): 66.4 ± 22.9 and Δ diastolic blood pressure [DBP]: 45.0 ± 13.5 mmHg). ARV and CV were highest with nurses’ measurements (SBP-ARV 9.2 ± 6.2; DBP-ARV 6.9 ± 5.2; SBP-CV 7.6 ± 5.3; DBP-CV 9.6 ± 5.5). The strongest correlation was found comparing physicians’ SBP measurements and 24hBPM ARVs (R2 0.23, P <.05). 24hBPM ΔSBP in a multivariate analysis was significantly associated with age (β −3.85, SE 0.83; P <.001) and PWV (β 20.29, SE 3.70; P <.001). Calcium antagonists were associated with a lower ΔSBP (β −14.6, SE 6.1, P <.05) while diuretics and alpha-blockers with a significant increase (β 14.4 SE 5.4, P <.01; β 26.9 SE 11.7, P <.05).

Age, PWV, diuretics, alpha-blockers, but also measurements obtained by nurses, increase BP variability while calcium antagonists reduce it. BP profiles in elderly in-hospital patients potentially provide important information; they should, however, be interpreted cautiously.
Asymmetrical bilateral sternoclavicular joint dislocation combined with bilateral clavicular fracture
Authors: Wang Haifeng , Wang Chongyang , Ruan Jianwei , Wu Weiqian
Published: July 2019

Rationale:

Asymmetrical bilateral sternoclavicular joint (SCJ) dislocation consists of posterior SCJ dislocation on one side and anterior SCJ dislocation on the other side. This is an extremely rare injury and only a few cases have been reported in the literature. If not been diagnosed timely and accurately, asymmetrical bilateral SCJ dislocation can be life-threatening.

Patients concerns:

We experienced a patient who has a life-threatening posterior dislocation of right SCJ and anterior dislocation on the left SCJ combined with bilateral clavicular fracture after a traffic accident.

Diagnoses:

A computed tomography (CT) scan with three-dimensional reconstructions of SCJ showed potentially life-threatening posterior dislocation of right SCJ and anterior dislocation on the left SCJ combined with bilateral clavicular fracture.

Interventions:

Because of failed attempts at closed reduction, electively surgical intervention was made. We repaired the ruptured joint capsule and ligaments and fixed bilateral SCJ by Kirschner wire during the operation.

Outcomes:

Three-dimensional CT scans confirmed bilateral SCJ reduction and alignment after operation 1 week as well as at the 2-month follow-up.

Lessons:

SCJ dislocation is an extremely rare and life-threatening injury. The aim of the operation is to repair the ruptured joint capsule and its ligaments and to fix the dislocated joints.
Severe hypoglycemia and hyponatremia caused by hypopituitarism in a female patient with type 1 diabetes
Authors: Zheng Fangqiu , Qiu Mingcai , Wei Hongyan
Published: July 2019

Rationale:

The misdiagnosis of hypopituitarism is common due to its rarity and its nonspecific clinical manifestations. Our case report highlights the importance of critical evaluation regarding hypopituitarism as a cause of recurrent hypoglycemia, hyponatremia, and gastrointestinal symptoms in patients with T1DM, as misdiagnosis might be fatal to the patient.

Patient concerns:

We herein report the case of 35-year-old female patient who presented with 18 years of history of well-controlled type 1 diabetes mellitus and a 6-month history of recurrent nausea and vomiting, generalized weakness, hyponatremia, and severe hypoglycemia, despite a reduction in the dose of insulin. She was considered as having “type 1 diabetes and gastroparesis.” Four months later, she was diagnosed with hypothyroidism, and 25 μg/d of levothyroxine was prescribed. However, the levothyroxine had to be discontinued 1 week later because of frequent vomiting by the patient.

Diagnosis:

Further evaluation in our hospital revealed low-normal adrenocorticotropic hormone, low-normal serum cortisol, and low 24-hours urinary cortisol excretion. Secondary hypothyroidism and hypogonadotropic hypogonadism were also demonstrated. Based on the endocrinological findings, she was diagnosed with hypopituitarism possibly due to lymphocytic hypophysitis. Diabetic nephropathy was another diagnosis made after kidney biopsy.

Interventions:

The patient was treated with 100 mg/d of hydrocortisone intravenously for 2 weeks. After that, she continued on 15 mg/d of prednisone, and then 25 μg/d of levothyroxine was administered.

Outcomes:

The patient's insulin requirement increased to a premorbid level, the severe hypoglycemia resolved, the physical discomforts were alleviated, and blood electrolytes returned to normal.

Lessons:

This uncommon case reinforced the significance of a timely diagnosis and appropriate treatment of hypopituitarism. We recommend that physicians focus their awareness on this potentially life-threatening disease, as it is a condition potentially fatal to the patient if not recognized and treated.
Gitelman's syndrome with hyperphosphatemia, effectively responding to single oral magnesium oxide administration
Authors: Miya Aika , Nakamura Akinobu , Kameda Hiraku , Nozu Kandai , Miyoshi Hideaki , Atsumi Tatsuya
Published: July 2019

Rationale:

The Gitelman's syndrome (GS) is characterized by metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria. However, the involvement of this deranged electrolyte balance in patients with GS in parathyroid hormone action has not been known.

Patient concerns:

We report a 34-year-old woman with muscle weakness and tetany/seizures caused by electrolyte imbalance. She had hyperphosphatemia and hypocalciuric hypocalcemia in addition to severe hypomagnesemia with low potassium in the absence of metabolic alkalosis. We identified 2 heterozygous mutations in the solute carrier family 12 member 3 gene in this case (c.1732G>A, p.Val578Met and c.2537_38delTT, p.846fs) by targeted sequence for all causative genes of salt-losing tubulopathies.

Diagnoses:

A diagnosis of GS. Hypocalcemia and hyperphosphatemia were suggested to relate with the secondary obstruction of appropriate parathyroid hormone release following severe hypomagnesemia in GS.

Interventions:

She was treated with single oral magnesium oxide administration.

Outcomes:

The electrolyte imbalance including hypocalcemia and hyperphosphatemia were resolved with a remission of clinical manifestations.

Lessons:

These observations, in this case, suggest that even severe hypomagnesemia caused by GS was associated with resistance to appropriate parathyroid hormone secretion. Through this case, we recognize that secondary hypoparathyroidism would be triggered by severe hypomagnesemia in GS.
Male primary mediastinal choriocarcinoma with diffuse metastases
Authors: Qiu Zhenhua , Wu Yuanqiang , Wang Yapeng , Hu Chunhong
Published: July 2019

Rationale:

Choriocarcinoma is a rare and highly invasive gestational trophoblastic tumor that secretes high levels of human chorionic gonadotropin (hCG). As one of the uncommon non-gestational choriocarcinoma, primary mediastinal choriocarcinoma is an exceeding rare, and aggressive malignancy with poor prognosis.

Patient concerns:

A 26-year-old man was admitted to the hospital with cough, shortness of breath, and occasional hemoptysis.

Diagnoses and intervention:

Imaging examinations revealed a large mediastinal mass, diffuse nodular opacities with blurred edges in both lungs, and multiple brain lesions. Laboratory tests showed an astonishing increase of serum β-hCG. A diagnosis of primary mediastinal choriocarcinoma with advanced lung and brain metastases was finally made after 3 biopsies and immunohistochemical analyses. Surgery and radiotherapy were not applicable at the time of diagnosis, and both targeted therapy and immunotherapy were unavailable. During the first 4 cycles of trophoblastic tumor-based chemotherapy, the patient improved clinically with fewer symptoms, decreased β-hCG and reduced lesions. However, drug resistance quickly emerged, forcing an alternative chemotherapy regimen that also failed.

Outcomes:

The patient finally endured symptoms including headache, dizziness and vomiting, and subsequently succumbed after an overall survival time of six and half months.

Lessons:

Male primary choriocarcinoma is an extremely rare type of malignancy. Greater awareness, earlier diagnosis and novel treatments are urgently needed to benefit patients.
Ultrasonographic imaging of calcifying fibrous tumor of cervical esophagus
Authors: Liu Yan , Lu Qiang , Wu Xiao-Li , Shen Guo-Ju , Luo Tao
Published: July 2019

Rationale:

Calcifying fibrous tumor (CFT) is a rare benign mesenchymal tumor characterized by cytologically benign fibroblasts that produce abundant collagen with scattered lymphocytes, plasma cells, and psammomatous or dystrophic calcifications.

Patient concerns:

A 37 years old women was initially diagnosed thyroid nodule in local hospital. She was referred to receive microwave ablation of the nodule in our hospital. The patient was in good health with occasional foreign body sensation in the neck. Routine laboratory examination was normal.

Diagnosis:

The lesion was suspected benign and originating from the esophagus rather than the thyroid gland by conventional ultrasound and contrast-enhanced ultrasound in our hospital and was finally proved to be CFT by pathology.

Interventions:

The lesion was surgically removed.

Outcomes:

The patient recovered well and was followed up for 2 years without recurrence.

Lessons:

Although imaging diagnosis of CFT is difficult, the findings of clear border, coarse calcification on conventional ultrasound and peripheral hypoenhancement without central enhancement on contrast-enhanced ultrasound (CEUS), together with real-time evaluation of the relationship between the tumor and esophagus help to distinguish CFT of cervical esophagus from other lesions in the neck.
The effect of fecal microbiota transplantation on Hepatic myelopathy
Authors: Sun Lin , Li Jun , Lan Li-Li , Li Xiao-An
Published: July 2019

Rationale:

Hepatic myelopathy (HM), also known as portal-systemic myelopathy, is a rare neurological complication that occurs in patients with chronic liver disease. There is no easy and feasible treatment, liver transplantation is the only accepted therapy that may be effective for patients at early stage at present. The pathogenesis of the disease is not clear yet, and the prognosis is poor. Here we describe a reversible HM after fecal microbiota transplantation.

Patient concerns:

In this report, a middle-aged female patient with hepatitis B cirrhosis, occurred HM after transjugular intrahepatic portosystemic shunt, a progressive spastic paraparesis in both legs were the main symptoms.

Diagnosis:

The patient was diagnosed with HM.

Interventions:

The patient received 3 times of fecal microbiota transplantations (FMT).

Outcomes:

The patient's muscle strength of both legs were increased at various degrees, the patient's condition improved from HM2 to HM1.

Lessons:

FMT may be another effective way to treat HM. It is cheaper, more operable, and simpler than the approved treatment and worthy of further research.
Chinese oral herbal paste for the treatment of stable chronic obstructive pulmonary disease
Authors: Zeng Yan , Li Yu , Wei Hua , Xiong Chan , Liao Li , Miao Ti-wei , Mao Bing , Fu Juan-juan
Published: July 2019

Background:

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with high morbidity and mortality placing heavy social and economic burden. As a kind of complementary therapy for the treatment of stable COPD, Chinese oral herbal paste has been widely used and studied. The study aims to evaluate the clinical efficacy and safety of herbal paste in the treatment of stable COPD, and to provide evidence for its clinical application.

Methods:

We will electronically search databases, including Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, EMBASE, PubMed, Chinese National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Scientific and Technological Periodical Database (VIP), and Chinese Biomedical Database (CBM), from respective inception to June 2019 to collect randomized controlled trials (RCTs) of Chinese oral herbal paste for the treatment of stable COPD. The websites of Chinese clinical trial registry and international clinical trial registry, the reference lists of the retrieved articles, conference proceedings, and gray literature will also be collected. The quality of life, symptom scores, and exacerbation frequency will be measured as primary outcomes. Secondary outcomes include scores of traditional Chinese medicine (TCM) syndrome, clinical effective rates according to criteria in TCM, changes in lung function, 6-minute walking distance, and safety analysis. The Cochrane bias risk assessment and the GRADE method will be used to assess the quality of the original studies included. Merging analysis of data will be performed using Rev Man 5.3 software.

Results:

The systematic review will provide an evidence on the clinical efficacy and safety of Chinese oral herbal paste for the treatment of stable COPD, and will be submitted for publication in a peer-reviewed journal.

Conclusion:

The study will confirm whether Chinese oral herbal paste is an effective and safe intervention for the prevention and treatment of stable COPD.
Association between endotoxemia and enterocyte injury and clinical course in patients with gram-positive septic shock
Authors: Sekino Motohiro , Funaoka Hiroyuki , Sato Shuntaro , Egashira Takashi , Inoue Haruka , Yano Rintaro , Matsumoto Sojiro , Ichinomiya Taiga , Higashijima Ushio , Matsumoto Shuhei , Hara Tetsuya
Published: July 2019

Endotoxemia often occurs in patients with gram-positive infections. The possible mechanism is thought to be bacterial translocation after enterocyte hypoperfusion injury. However, the association between endotoxemia and enterocyte injury among patients with gram-positive septic shock has never been assessed. The aim of this study was to evaluate the association between endotoxemia and enterocyte injury in gram-positive septic shock patients and to evaluate the association among endotoxemia, subsequent clinical course, and other related factors.

This was a posthoc analysis of a prospective observational study that evaluated the capability of intestinal fatty acid-binding protein (I-FABP), an indicator of enterocyte injury, to predict mortality. Among 57 patients in septic shock, those whose causative microorganisms were gram positive were included. The correlation between endotoxin activity (EA), which indicates endotoxemia, and I-FABP levels upon admission to the intensive care unit (ICU), the clinical course, and other related factors were evaluated.

A total of 21 patients were examined. One-third of the patients presented with high EA levels at the time of ICU admission. However, there was no significant correlation between EA and I-FABP levels (Spearman ρ = 0.002, P = .993). Additionally, high EA levels were not associated with abdominal complications after ICU admission or mortality. Similarly, high EA levels were not associated with severity scores, inotropic scores, or lactate levels upon ICU admission, which were previously reported to be factors related to high EA levels.

In this posthoc analysis, no correlation was observed between endotoxemia and enterocyte injury among patients in gram-positive septic shock. Additionally, high EA levels were not associated with the clinical course and reported factors related to endotoxemia. Although our results need to be validated in a large prospective cohort study, hypoperfusion enterocyte injury might not be a cause of endotoxemia in these patients. Thus, if there is no correlation between EA and I-FABP levels, other mechanisms that induce high EA levels among patients with gram-positive septic shock should be elucidated.
First-stage scapholunate fusion for the treatment of a chronic lunate dislocation
Authors: Huang Chao , You Di , Guo Wenlai , Qu Wenrui , Hu Yuchen , Li Rui , Zhu Zhe
Published: July 2019

Rationale:

Lunate dislocation is a rare injury to the wrist caused by high-energy trauma, and poor prognosis is often associated with missed initial diagnosis. To date, there is no consensus regarding an effective treatment plan for such cases.

Patient concerns:

Here, we describe the case of a 36-year-old man who presented with lunate dislocation following a delay in diagnosis of over 7 weeks, and further illuminate its diagnosis and treatment.

Diagnosis:

The diagnosis of chronic lunate dislocation was rendered.

Interventions:

The patient was treated using reduction via the dorsal approach brachial plexus anesthesia. After the reduction, a headless compression screw fixation was performed for first-stage scapholunate fusion, and Kirschner wire fixation of the lunate-triquetrum-hamate was used to stabilize the distal and proximal carpal rows.

Outcomes:

The patient was followed up for 1 year and showed wrist function recovered well; radiographic examination showed no lunate dislocation and successful scapholunate bony fusion. A satisfactory outcome was achieved.

Lessons:

The case study presented here provide evidence that performing an effective first-stage scapholunate fusion is recommended to achieve better therapeutic outcomes for a chronic lunate dislocation. Furthermore, this approach led to a good long-term clinical outcome in our case.
The Successful Sequential Use of Plerixafor and Eltrombopag For Hematopoietic Cell Transplantation in a Child With High-risk Neuroblastoma
Authors: Marjanska Agata , Czyzewski Krzysztof , Debski Robert , Krenska Anna , Wysocki Mariusz , Styczynski Jan
Published: July 2019

High-dose chemotherapy with autologous hematopoietic stem cell transplantation improves event-free survival in patients with high-risk neuroblastoma. However, in heavily pretreated patients, poor marrow function can be an obstacle in the successful proceeding of therapy. Priming with plerixafor plus filgrastim is an option for effective mobilization and collection of stem cells. In addition, thrombopoietin agonist eltrombopag can improve the outcome of posttransplantation thrombocytopenia and poor graft function in the posttransplant setting. We describe a case of a child with high-risk neuroblastoma, for whom plerixafor and eltrombopag were used as an effective and safe supportive therapy.
Dilemma of Gonial Angle in Sex Determination
Authors: Bulut Ozgur , Freudenstein Nicolle , Hekimoglu Baki , Gurcan Safa
Published: July 2019

Background and Aim

The determination of sex from human remains has a crucial role in forensic anthropology. It has been known that the mandible has several useful traits for sex determination. The gonial angle, which is one of them, has been evaluated by forensic practitioners to identify sexual dimorphism with morphologic and metrical analyses. However, there are opposing approaches on the sexual dimorphism of the gonial angle in the literature, which contradict each other. There are also some other studies asserting that it cannot be employed in sex determination. The purpose of this study is first to figure out the reason for this dilemma and then establish the significance of the gonial angle in sex determination in a white sample.

Methods

Computed tomography scans were obtained from 300 adults (150 males and 150 females), which were divided into 3 age groups (20–39, 40–59, 60–80 years). The gonial angle, which is formed by 2 lines: (1) between the most posterior point of the mandibular condyle and the gonion and (2) between the most inferior point of the mandibular symphysis and gonion, was measured on computed tomography scans. In order to observe differences among the 3 age groups, the collected data were analyzed using 1-way analysis of variance followed by a least significant difference post hoc test. Two-way analysis of variance was used to compare sex differences in each age group.

Discussion

It is suggested that the probable reason of this dilemma is the unsubtle samples of the researches. Categorizing the sample into age groups with statistically sufficient number makes the data more valuable in terms of examining the differences related to sexual dimorphism. This study also reported that males showed slightly smaller gonial angle values than those of females in all age groups. No statistically significant difference was observed in the gonial anthropometric values for middle age groups (20–39 and 40–59 years), whereas it shows statistically sexual dimorphism for senior adult group (60–80 years). However, the results revealed that the gonial angle is not a particularly good indicator to identify the sex from the cranium and should not be used as a sole criterion.