Efficacy of Gastric Balloon Dilatation and/or Retrievable Stent Insertion for Pyloric Spasms after Pylorus-Preserving Gastrectomy: Retrospective Analysis

Purpose

We retrospectively investigated the feasibility and clinical efficacy of balloon dilatation and subsequent retrievable stent insertion, when necessitated, for pyloric spasms after pylorus-preserving gastrectomy (PPG).

Materials and Methods

Forty-five patients experiencing pyloric spasms after PPG underwent fluoroscopic balloon dilations to alleviate obstructive symptoms due to delayed gastric emptying. Patients showing poor response to balloon dilation underwent subsequent retrievable stent insertion. Safety of the procedures was analyzed, and subjective symptoms and objective signs of pyloric spasms were analyzed and compared before and after treatment.

Results

Thirty-three patients (73.3%, 33/45) showed good response to balloon dilatation requiring no further treatment (balloon group). Conversely, 12 patients (26.7%, 12/45) showed poor or no response after balloon dilation requiring subsequent stent insertion (stent group). Balloon dilations and/or stent insertions were safely performed in all patients except one patient who suffered a transmural tear after balloon dilatation. In both groups, mean subjective symptom score was significantly improved and mean pyloric canal-to-height of the adjacent vertebral body ratio was significantly increased after the procedures (P <.05).

Conclusion

Balloon dilation is a safe and effective treatment for patients with pyloric spasms after PPG. In patients refractory to balloon dilations, retrievable stent placement can be a safe alternative tool.     

Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy

Objective

Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

Methods

A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m² as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up.

Results

Patients were followed up to an average age of 15.9 ± 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027).

Conclusions

We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts.     

Vitamin A deficiency alters the pulmonary parenchymal elastic modulus and elastic fiber concentration in rats

Background

Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. Vitamin A deficiency (VAD) is associated with an increase in airway hyperreactivity in rats and a decrease in the volume density of alveoli and alveolar ducts. To better define the effects of VAD on the mechanical properties of the pulmonary parenchyma, we have studied the elastic modulus, elastic fibers and elastin gene-expression in rats with VAD, which were supplemented with retinoic acid (RA) or remained unsupplemented.

Methods

Parenchymal mechanics were assessed before and after the administration of carbamylcholine (CCh) by determining the bulk and shear moduli of lungs that that had been removed from rats which were vitamin A deficient or received a control diet. Elastin mRNA and insoluble elastin were quantified and elastic fibers were enumerated using morphometric methods. Additional morphometric studies were performed to assess airway contraction and alveolar distortion.

Results

VAD produced an approximately 2-fold augmentation in the CCh-mediated increase of the bulk modulus and a significant dampening of the increase in shear modulus after CCh, compared to vitamin A sufficient (VAS) rats. RA-supplementation for up to 21 days did not reverse the effects of VAD on the elastic modulus. VAD was also associated with a decrease in the concentration of parenchymal elastic fibers, which was restored and was accompanied by an increase in tropoelastin mRNA after 12 days of RA-treatment. Lung elastin, which was resistant to 0.1 N NaOH at 98°, decreased in VAD and was not restored after 21 days of RA-treatment.

Conclusion

Alterations in parenchymal mechanics and structure contribute to bronchial hyperreactivity in VAD but they are not reversed by RA-treatment, in contrast to the VAD-related alterations in the airways.     

Absence of Tumor-Infiltrating Lymphocyte Is a Reproducible Predictive Factor for Sentinel Lymph Node Metastasis: A Multicenter Database Study by the Brazilian Melanoma Group

Aims

The aim of this study is to confirm the function of tumor-infiltrating lymphocytes (TILs) in sentinel lymph node (SLN) metastasis.

Materials and Methods

This retrospective study included 633 patients with invasive melanoma who underwent sentinel lymph node biopsy in 7 referral centers certified by the Brazilian Melanoma Group. Independent risk factors of sentinel node metastasis (SNL) were identified by multiple logistic regression.

Results

SLN metastasis was detected in 101 of 633 cases (16.1%) and in 93 of 428 patients (21.7%) when melanomas ≤ 1mm were excluded. By multiple logistic regression, the absence of TILs was as an independent risk factor of SLN metastasis (OR = 1.8; 95%CI: 1.1–3.0), in addition to Breslow index (greater than 2.00 mm), lymph vascular invasion, and presence of mitosis.

Conclusion

SLNB can identify patients who might benefit from immunotherapy, and the determination of predictors of SLNB positivity can help select the proper population for this type of therapy. The absence of TILs is a reproducible parameter that can predict SLNB positivity in melanoma patients, since this study was made with several centers with different dermatopathologists.     

Upregulated Polo-Like Kinase 1 Expression Correlates with Inferior Survival Outcomes in Rectal Cancer

Background

Human polo-like kinase 1 (PLK1) expression has been associated with inferior outcomes in colorectal cancer. Our aims were to analyse PLK1 in rectal cancer, and its association with clinicopathological variables, overall survival as well as tumour regression to neoadjuvant treatment.

Methods

PLK1 expression was quantified with immunohistochemistry in the centre and periphery (invasive front) of rectal cancers, as well as in the involved regional lymph nodes from 286 patients. Scores were based on staining intensity and percentage of positive cells, multiplied to give weighted scores from 1–12, dichotomised into low (0–5) or high (6–12).

Results

PLK1 scores in the tumour periphery were significantly different to adjacent normal mucosa. Survival analysis revealed that low PLK1 score in the tumour periphery had a hazard ratio of death of 0.59 in multivariate analysis. Other predictors of survival included age, tumour depth, metastatic status, vascular and perineural invasion and adjuvant chemotherapy. There was no statistically significant correlation between PLK1 score and histological tumour regression in the neoadjuvant cohort.

Conclusion

Low PLK1 score was an independent predictor of superior overall survival, adjusting for multiple clinicopathological variables including treatment.     

Determination of the Optimal Dose Reduction Level via Iterative Reconstruction Using 640-Slice Volume Chest CT in a Pig Model

Aim

To determine the optimal dose reduction level of iterative reconstruction technique for paediatric chest CT in pig models.

Materials and Methods

27 infant pigs underwent 640-slice volume chest CT with 80kVp and different mAs. Automatic exposure control technique was used, and the index of noise was set to SD10 (Group A, routine dose), SD12.5, SD15, SD17.5, SD20 (Groups from B to E) to reduce dose respectively. Group A was reconstructed with filtered back projection (FBP), and Groups from B to E were reconstructed using iterative reconstruction (IR). Objective and subjective image quality (IQ) among groups were compared to determine an optimal radiation reduction level.

Results

The noise and signal-to-noise ratio (SNR) in Group D had no significant statistical difference from that in Group A (P = 1.0). The scores of subjective IQ in Group A were not significantly different from those in Group D (P>0.05). There were no obvious statistical differences in the objective and subjective index values among the subgroups (small, medium and large subgroups) of Group D. The effective dose (ED) of Group D was 58.9% lower than that of Group A (0.20±0.05mSv vs 0.48±0.10mSv, p <0.001).

Conclusions

In infant pig chest CT, using iterative reconstruction can provide diagnostic image quality; furthermore, it can reduce the dosage by 58.9%.     

Multi-Morbidity in Hospitalised Older Patients: Who Are the Complex Elderly?

Background

No formal definition for the “complex elderly” exists; moreover, these older patients with high levels of multi-morbidity are not readily identified as such at point of hospitalisation, thus missing a valuable opportunity to manage the older patient appropriately within the hospital setting.

Objectives

To empirically identify the complex elderly patient based on degree of multi-morbidity.

Design

Retrospective observational study using administrative data.

Setting

English hospitals during the financial year 2012–13.

Subjects

All admitted patients aged 65 years and over.

Methods

By using exploratory analysis (correspondence analysis) we identify multi-morbidity groups based on 20 target conditions whose hospital prevalence was ≥ 1%.

Results

We examined a total of 2788900 hospital admissions. Multi-morbidity was highly prevalent, 62.8% had 2 or more of the targeted conditions while 4.7% had six or more. Multi-morbidity increased with age from 56% (65-69yr age-groups) up to 67% (80-84yr age-group). The average multi-morbidity was 3.2±1.2 (SD). Correspondence analysis revealed 3 distinct groups of older patients. Group 1 (multi-morbidity ≤2), associated with cancer and/or metastasis; Group 2 (multi-morbidity of 3, 4 or 5), associated with chronic pulmonary disease, lung disease, rheumatism and osteoporosis; finally Group 3 with the highest level of multi-morbidity (≥6) and associated with heart failure, cerebrovascular accident, diabetes, hypertension and myocardial infarction.

Conclusions

By using widely available hospital administrative data, we propose patients in Groups 2 and 3 to be identified as the complex elderly. Identification of multi-morbidity patterns can help to predict the needs of the older patient and improve resource provision.     

A Pilot Study to Propose a "Harm Scale", a New Method to Predict Risk of Harm to the Corneal Endothelium Caused by Longitudinal Phacoemulsification,and the Subsequent Effect of Endothelial Damage on Post Operative Visual Acuity

Purpose

To study the effect of longitudinal phacoemulsification energy on corneal endothelium and to evaluate the relationship between changes of endothelial cells and postoperative visual acuity.

Methods

This prospective clinical observational cohort study included 50 patients with cataract who underwent longitudinal phacoemulsification. Sequential quantitative and qualitative morphometric endothelial cell analyses of the cornea were performed 4 weeks preoperatively and 6 weeks postoperatively using noncontact specular microscopy.

Results

There was a relationship between ECL percentage (ECL%) and the 5-score harm scale, well-described by a linear model (one-way ANOVA, R² = 73.3%). Analyzing the distribution of ECL% Mean with Tukey post-hoc pairwise comparison test (P < 0.001), the value of ECL = 20% has been regarded as cut-off to discriminate patients who obtained an excellent postoperative best-corrected visual acuity (BCVA > 85 letters) from those who just had a good visual outcome (BCVA ≤ 85 letters). There was a significant correlation among the 5-score harm scale, phaco energy intraoperatively delivered, and average cell area postoperatively.

Conclusions

The 5-score harm scale, a new method that enables to pigeonhole cataracts taking into account nucleus hardness and phaco times, allows to predict the harm on corneal endothelium after longitudinal phacoemulsification. Assessment of ECL% permits to discriminate between patients with excellent BCVA and with just good BCVA, postoperatively.     

Impact of Postoperative Chemoradiotherapy versus Chemotherapy Alone on Recurrence and Survival in Patients with Stage II and III Upper Rectal Cancer: A Propensity Score-Matched Analysis

Purpose

To compare the impact of postoperative chemoradiotherapy (CRT) versus adjuvant chemotherapy alone on recurrence and survival in patients with stage II and III upper rectal cancer undergoing curative resection.

Materials and Methods

From our institutional database, 190 patients who underwent primary curative resection between 2003 and 2010 for stage II or III upper rectal cancer were identified. None of the patients received preoperative CRT. Of these, 136 patients received postoperative chemotherapy alone (the CTx group) and 54 patients received postoperative CRT (the CRT group). The CRT group had poorer prognostic features (pT4, pN2, poor differentiation, or involved resection margin) compared with the CTx group. To reduce the impact of treatment selection bias on treatment outcomes, propensity score-matching analysis was used.

Results

The matched cohort consisted of 50 CRT and 50 CTx patients with a median follow-up period of 76 and 63 months, respectively. In the matched cohort, CRT resulted in an improved 5-year local control (98.0% vs. 85.2%, p = 0.024) and overall survival rate (89.9% vs. 69.8%, p = 0.021) compared with CTx. In the subgroup analysis to identify subpopulations of patients that benefit most from receiving CRT, local recurrence did not occur in patients who did not have poor prognostic features regardless of the receipt of CRT. For patients with any poor prognostic features, CRT resulted in an improved 5-year local control compared with CTx (96.4% vs. 70.7%, p = 0.013).

Conclusions

After adjusting for clinicopathologic factors by propensity score-matching, postoperative CRT was associated with improved local control and overall survival in stage II and III upper rectal cancer. Our results suggest that surgery followed by chemotherapy alone is acceptable for patients who did not have poor prognostic features, while additional radiotherapy should be given for patients who have any poor prognostic features.     

Clinicopathological Characteristics and Survival Outcomes of Primary Signet Ring Cell Carcinoma in the Stomach: Retrospective Analysis of Single Center Database

Purpose

To investigate the clinicopathological features and prognosis of signet ring cell carcinoma of the stomach (SRC).

Methods

A total of 1464 gastric cancer patients who underwent curative gastrectomy from 2000 to 2008 at a single center were evaluated. Signet ring cell carcinoma (SRC) was defined as the presence of at least 50% signet ring cells in the pathologic specimen. The clinicopathological parameters and prognosis of SRC were analyzed by comparing with non-signet ring cell carcinoma (NSRC).

Results

Of 1464 patients, 138 patients (9.4%) were classified as SRC. There were significant differences in gender, age, tumor location, TNM stage, p21 expression, and p53 expression between SRC and NSRC. The 5-year survival rates of SRC and NSRC were 36.2% and 49.5%, respectively. The prognosis of SRC was poorer than that of NSRC (P <0.001). Multivariate analysis showed that SRC histology was an independent factor for poor prognosis (P <0.001).

Conclusion

Patients with SRC tend to present with a more advanced stage and poorer prognosis than patients with other types of gastric carcinoma.     

Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation,Migration and Invasion

Objectives

Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC.

Materials and Methods

Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman’s rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay.

Results

In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01) / clinical staging (r = -0.41, P<0.01) / tumor stage (r = -0.28, P = 0.02) / nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells.

Conclusion

Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC.     

Association between Lymph Node Ratio and Disease Specific Survival in Breast Cancer Patients with One or Two Positive Lymph Nodes Stratified by Different Local Treatment Modalities

Purpose

Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial indicated that complete axillary node dissection (ALND) may not be warranted in some breast cancer patients with low tumor burden who are undergoing breast-conserving surgery following whole-breast irradiation. However, this study did not address patients undergoing mastectomy or those undergoing breast-conserving surgery without whole-breast radiotherapy. Given that lymph node ratio (LNR; ratio of positive lymph nodes to the total number removed) has been shown to be a prognostic factor in breast cancer, we first sought to determine the prognostic value of LNR in a low risk population comparable to that of the Z0011 trial and further to investigate whether the prognostic significance differs with local treatment modality.

Method

We used the Surveillance Epidemiology and End Results (SEER) database to identify breast cancer patients with T1-T2 tumor and 1–2 positive nodes. Patients were subclassified by the local therapy they underwent for the primary tumor. The prognostic value of LNR in predicting disease-specific survival (DSS) was examined in each treatment group.

Results

A total of 53,109 patients were included. In the subgroup of 20,602 patients who underwent lumpectomy following radiotherapy, LNR was not found to be significantly associated with DSS in both the univariate and multivariate model. For the 4,664 patients treated with mastectomy following radiotherapy, 6,811 treated with lumpectomy without radiotherapy and 21,031 with mastectomy without radiotherapy, LNR independently predict DSS in each of these subgroups.

Conclusions

Our results add evidence to the concept that axillary dissection could be omitted in patients with one or two positive nodes following breast-conserving surgery and whole breast radiation.     

Value of Dynamic Susceptibility Contrast Perfusion MRI in the Acute Phase of Transient Global Amnesia

Purpose

Transient global amnesia (TGA) is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI) in TGA in the acute phase.

Methods

From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF) and volume (CBV)) were generated and analyzed by use of Signal Processing In NMR-Software (SPIN). CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL).

Results

Five TGA patients were included (2 men, 3 women). On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus.

Conclusions

Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in larger data sets and serial PWI examinations.     

Application of Ureteroscope in Emergency Treatment with Persistent Renal Colic Patients during Pregnancy

Background

Although the application of ureteroscopy in the treatment of ureteral calculi during pregnancy has been on the rise, for persistent renal colic patients without ultrasound-detected ureteral calculi, it may represent a clinical dilemma due to the potential risks for both mother and fetus.

Objective

The aim of the present study is to present our experience with the application of the ureteroscope in the emergency treatment of persistent renal colic patients during pregnancy.

Methods

From March 2009 to September 2014, a total of 117 pregnant women who received ureteroscopy for persistent renal colic were retrospectively analyzed. Patients were divided into three groups according to duration of the persistent renal colic: Group A (within 12 hours; 24 cases); Group B (12 to 24 hours; 76 cases); and Group C (more than 24 hours; 17 cases). The stone-free rate, complications, and other qualitative data were analyzed.

Results

Of the 117 patients, 31 patients who were found not to have renal or ureteral calculi received ureteroscopic double-J (DJ) stent insertion, whereas 86 patients who were found with ureteral calculi received ureteroscopic lithotripsy (URSL) and DJ stent insertion. Among them, 24 patients (27.9%) were found with ureteral calculi by ureteroscopy rather than ultrasound. In addition, 73 patients (84.9%) had complete fragmentation of calculi; 12 patients (10.3%) had a threatened abortion (the rates of threatened abortion in Groups A, B and C were 8.3% vs. 6.5% vs. 29.4%; Group C compared with Groups A and B, p<0.05), and one patient (1.2%) had urosepsis (in Group C). However, these complications were cured with conservative treatment, without postpartum infant and maternal complications.

Conclusion

For pregnant patients with persistent renal colic/ureteral calculi and hydronephrosis, ureteroscopic DJ stent insertion and URSL are effective and safe options when conservative treatment fails, even if no urinary calculi were found by ultrasound. At the same time, for patients with persistent renal colic during pregnancy, early application of ureteroscopy may reduce the risk of preterm birth.     

Sleep Quality of Patients with Differentiated Thyroid Cancer

Objective

We aimed to measure prevalence of sleep disturbance in patients with differentiated thyroid cancer (DTC) by calculating Pittsburgh Sleep Quality Index (PSQI), and compare these data with patients with benign thyroid nodules or normal participants.

Methods

Three groups of patients participated in this cross-sectional study. In the first group, 162 patients with DTC received total thyroidectomy, and then ¹³¹I therapy. The second group consisted of 84 patients with benign thyroid nodules, who received partial thyroidectomy. The third group was 78 normal healthy control cases. PSQI was used to assess the sleep quality. Inter-group differences were analyzed by Kruskal-Wallis test or independent samples T test. χ² test was also used to check prevalence differences of poor sleep quality among the groups. Differences of PSQI score and poor sleep quality prevalence before and after ¹³¹I therapy in the same group of DTC participants were analyzed by paired T test and Mcnemar''s test.

Results

Higher PSQI score (7.59 ± 4.21) and higher rate of poor sleep quality (54.32%) were shown in DTC patients than in any other group. After ¹³¹I therapy, PSQI score and prevalence of poor sleep quality in DTC patients increased significantly to 8.78 ± 4.72 and 70.99%. Then DTC patients were divided into two subgroups based on their metastatic status. DTC patients with metastasis (87/162 cases, 53.70%) had significantly higher PSQI score (10.87 ± 5.18) and higher prevalence of poor sleep quality (79.31%).

Conclusion

DTC patients suffer from sleep disturbance, ¹³¹I therapy and awareness of metastatic status could worsen sleep problem. Psychological fear of cancer, nuclear medicine therapy and metastasis could be one major underlying reason. Longitude and interventional studies are necessary for further investigations.     

A Randomized Controlled Trial of a Brief Intervention for Delayed Psychological Effects in Snakebite Victims

Background

Snakebite results in delayed psychological morbidity and negative psycho-social impact. However, psychological support is rarely provided to victims.

Aim

To assess the effectiveness of a brief intervention which can be provided by non-specialist doctors aimed at reducing psychological morbidity following snakebite envenoming.

Method

In a single blind, randomized controlled trial, snakebite victims with systemic envenoming [n = 225, 168 males, mean age 42.1 (SD 12.4) years] were randomized into three arms. One arm received no intervention (n = 68, Group A), the second received psychological first aid and psychoeducation (dispelling prevalent cultural beliefs related to snakebite which promote development of a sick role) at discharge from hospital (n = 65, Group B), while the third received psychological first aid and psychoeducation at discharge and a second intervention one month later based on cognitive behavioural principles (n = 69, Group C). All patients were assessed six months after hospital discharge for the presence of psychological symptoms and level of functioning using standardized tools.

Results

At six months, there was a decreasing trend in the proportion of patients who were positive for psychiatric symptoms of depression and anxiety from Group A through Group B to Group C (Chi square test for trend = 7.901, p = 0.005). This was mainly due to a decreasing trend for symptoms of anxiety (chi-square for trend = 11.256, p = 0.001). There was also decreasing trend in the overall prevalence of disability from Group A through Group B to Group C (chi square for trend = 7.551, p = 0.006), predominantly in relation to disability in family life (p = 0.006) and social life (p = 0.005). However, there was no difference in the proportion of patients diagnosed with depression between the three groups (chi square for trend = 0.391, p = 0.532), and the intervention also had no effect on post-traumatic stress disorder.

Conclusions

A brief psychological intervention, which included psychological first aid and psychoeducation plus cognitive behavioural therapy that can be provided by non-specialist doctors appeared to reduce psychiatric symptoms and disability after snakebite envenoming, but not depression or post-traumatic stress disorder.

Trial Registration

Sri Lanka Clinical Trials Registry: SLCTR/2011/003     

Fractal characteristics of May-Grünwald-Giemsa stained chromatin are independent prognostic factors for survival in multiple myeloma

Background

The use of computerized image analysis for the study of nuclear texture features has provided important prognostic information for several neoplasias. Recently fractal characteristics of the chromatin structure in routinely stained smears have shown to be independent prognostic factors in acute leukemia. In the present study we investigated the influence of the fractal dimension (FD) of chromatin on survival of patients with multiple myeloma.

Methodology

We analyzed 67 newly diagnosed patients from our Institution treated in the Brazilian Multiple Myeloma Study Group. Diagnostic work-up consisted of peripheral blood counts, bone marrow cytology, bone radiograms, serum biochemistry and cytogenetics. The International Staging System (ISS) was used. In every patient, at least 40 digital nuclear images from diagnostic May-Grünwald-Giemsa stained bone marrow smears were acquired and transformed into pseudo-3D images. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R² values in the log-log plots. The influence of diagnostic features on overall survival was analyzed in Cox regressions. Patients that underwent autologous bone marrow transplantation were censored at the day of transplantation.

Principal Findings

Median age was 56 years. According to ISS, 14% of the patients were stage I, 39% were stage II and 47% were stage III. Additional features of a bad prognosis were observed in 46% of the cases. When stratifying for ISS, both FD and its goodness-of-fit were significant prognostic factors in univariate analyses. Patients with higher FD values or lower goodness-of-fit showed a worse outcome. In the multivariate Cox-regression, FD, R², and ISS stage entered the final model, which showed to be stable in a bootstrap resampling study.

Conclusions

Fractal characteristics of the chromatin texture in routine cytological preparations revealed relevant prognostic information in patients with multiple myeloma.     

Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency

Background and Purpose

Ornithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks—default mode and set-maintenance—between OTCD patients and healthy controls.

Methods

Sixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.

Results

Group comparisons revealed reduced functional connectivity in the default mode network (DMN) of OTCD patients, particularly between the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) node and bilateral inferior parietal lobule (IPL), as well as between the ACC/mPFC node and the posterior cingulate cortex (PCC) node. Patients also showed reduced connectivity in the set-maintenance network, especially between right anterior insula/frontal operculum (aI/fO) node and bilateral superior frontal gyrus (SFG), as well as between the right aI/fO and ACC and between the ACC and right SFG.

Conclusion

Internodal functional connectivity in the DMN and set-maintenance network is reduced in patients with partial OTCD compared to controls, most likely due to hyperammonemia-related white matter damage. Because several of the affected areas are involved in executive functioning, it is postulated that this reduced connectivity is an underlying cause of the deficits OTCD patients display in this cognitive domain.     

Recovery of Corneal Endothelial Cells from Periphery after Injury

Background

Wound healing of the endothelium occurs through cell enlargement and migration. However, the peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium in endothelial injury.

Aim

To investigate the recovery process of corneal endothelial cells (CECs) from corneal endothelial injury.

Methods

Three patients with unilateral chemical eye injuries, and 15 rabbit eyes with corneal endothelial chemical injuries were studied. Slit lamp examination, specular microscopy, and ultrasound pachymetry were performed immediately after chemical injury and 1, 3, 6, and 9 months later. The anterior chambers of eyes from New Zealand white rabbits were injected with 0.1 mL of 0.05 N NaOH for 10 min (NaOH group). Corneal edema was evaluated at day 1, 7, and 14. Vital staining was performed using alizarin red and trypan blue.

Results

Specular microscopy did not reveal any corneal endothelial cells immediately after injury. Corneal edema subsided from the periphery to the center, CEC density increased, and central corneal thickness decreased over time. In the animal study, corneal edema was greater in the NaOH group compared to the control at both day 1 and day 7. At day 1, no CECs were detected at the center and periphery of the corneas in the NaOH group. Two weeks after injury, small, hexagonal CECs were detected in peripheral cornea, while CECs in mid-periphery were large and non-hexagonal.

Conclusions

CECs migrated from the periphery to the center of the cornea after endothelial injury. The peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium.     

Puncture Reduction in Percutaneous Transforaminal Endoscopic Discectomy with HE’s Lumbar LOcation (HELLO) System: A Cadaver Study

Background

Percutaneous transforaminal endoscopic discectomy (PTED) usually requires numerous punctures under X-ray fluoroscopy. Repeated puncture will lead to more radiation exposure and reduce the beginners'' confidence.

Objective

This cadaver study aimed to investigate the efficacy of HE’s Lumbar Location (HELLO) system in puncture reduction of PTED.

Study design

Cadaver study.

Setting

Comparative groups.

Methods

HELLO system consists of self-made surface locator and puncture locator. One senior surgeon conducted the puncture procedure of PTED on the left side of 20 cadavers at L4/L5 and L5/S1 level with the assistance of HELLO system (Group A). Additionally, the senior surgeon conducted the puncture procedure of PTED on the right side of the cadavers at L4/L5 and L5/S1 level with traditional methods (Group B). On the other hand, an inexperienced surgeon conducted the puncture procedure of PTED on the left side of the cadavers at L4/L5 and L5/S1 level with the assistance of our HELLO system (Group C).

Results

At L4/L5 level, there was significant difference in puncture times between Group A and Group B (P<0.001), but no significant difference was observed between Group A and Group C (P = 0.811). Similarly at L5/S1 level, there was significant difference in puncture times between Group A and Group B (P<0.001), but no significant difference was observed between Group A and Group C (P = 0.981). At L4/L5 level, there was significant difference in fluoroscopy time between Group A and Group B (P<0.001), but no significant difference was observed between Group A and Group C (P = 0.290). Similarly at L5/S1 level, there was significant difference in fluoroscopy time between Group A and Group B (P<0.001), but no significant difference was observed between Group A and Group C (P = 0.523). As for radiation exposure, HELLO system reduced 39%-45% radiation dosage when comparing Group A and Group B, but there was no significant difference in radiation exposure between Group A and Group C whatever at L4/L5 level or L5/S1 level (P>0.05). There was no difference in location time between Group A and Group B or Group A and Group C either at L4/L5 level or L5/S1 level (P>0.05).

Limitations

Small-sample preclinical study.

Conclusion

HELLO system was effective in reducing puncture times, fluoroscopy time and radiation exposure, as well as the difficulty of learning PTED. (2015-RES-127)