Correlations between Steady-State Pattern Electroretinogram and Humphrey Visual Field Analyzer Global Indices and Their Associations with Retinal Ganglion Cell Layer-Inner Plexiform Layer Thickness in Glaucoma Suspects.

Purpose: The purpose of this study was to investigate the utility of steady state pattern electroretinogram (ss-PERG) in detecting retinal ganglion cell (RGC) dysfunction in glaucoma suspects (GS) who had normal 24-2 Humphrey Visual Fields (HFA). Materials and Methods: This was a prospective cohort study of GS patients who were identified based on optic disc appearance with normal HFAs. Patients received a complete eye examination, standard automated perimetry (SAP), optical coherence tomography (OCT), and ss-PERG measurements. The ss-PERG parameters, Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio, were examined, along with their relationships between HFA and OCT measurements. Results: Twenty-five patients were included in this study, with a total of 49 eyes. Fifteen eyes had abnormal ss-PERG parameters and when compared to GS eyes with normal ss-PERG parameters, there were significant differences in HFA 24-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer and inner plexiform layer (GCL + IPL) thickness. All ss-PERG parameters were significantly correlated with 24-2 VF mean deviation (MD) and visual field index (VFI), as well as 10-2 VF MD after controlling for age, sex, intraocular pressure, central corneal thickness, and spherical equivalent. When controlled for age, spherical equivalent, and IOP, MagD/Mag ratio significantly contributed to the variance in average GCL + IPL thicknesses, whereas 24-2 VF MD and 10-2 VF MD did not. MagD/Mag ratio also significantly accounted for variance in all macular GCL + IPL sectors, while 10-2 VF MD did not. Conclusions: ss-PERG has significant correlations with HFA global indices and was predictive of GCL + IPL thickness in GS patients. Clinical Significance. ss-PERG may serve as a useful functional tool for detecting and measuring RGC dysfunction in GS. It appears to be more sensitive than HFA in the detection of early changes in GCL + IPL thicknesses and may be helpful to use in conjunction with current diagnostic studies to improve the ability of monitoring GS progression.

Associations between steady-state pattern electroretinography and estimated retinal ganglion cell count in glaucoma suspects.

PURPOSE: To estimate retinal ganglion cell (RGC) count in glaucoma suspects (GS) and ascertain its relationships with steady-state pattern electroretinography (ssPERG) parameters. METHODS: In this prospective cross-sectional study, 22 subjects (44 eyes) were recruited at the Manhattan Eye, Ear, and Throat Hospital. Subjects underwent complete eye examinations, optical coherence tomography, standard automated perimetry, and ssPERG testing. Eyes were divided into two groups based upon clinical data: healthy subjects and GS. RGC count was estimated using the combined structure-function index. RESULTS: Estimated RGC count, average retinal nerve fiber layer thickness (ARNFLT), and average ganglion cell layer and inner plexiform layer thickness (GCIPLT) were reduced in GS eyes (p ≤ 0.001 for all parameters). Pearson correlations revealed that ssPERG magnitude and magnitudeD correlated with ARNFLT (r ≥ 0.53, p < 0.001), GCIPLT (r > 0.38, p < 0.011), and estimated RGC count (r > 0.46, p < 0.002). Six mediation analyses revealed that estimated RGC count mediated the relationships among ssPERG parameters, ARNFLT, and GCIPLT. CONCLUSION: Steady-state PERG parameters demonstrated linear correlations with estimated RGC count. The associations among ssPERG parameters and structural measures were mediated by estimated RGC count.

Risk factors associated to intestinal anastomotic leakage in elective surgery.

BACKGROUND: The intestinal anastomotic leakage is the most feared surgical complication of a digestive surgery and is associated with a significant increase of morbidity, mortality and hospital stay. OBJECTIVE: Analyze the risk factors to the intestinal anastomotic leakage in elective surgery. METHOD: Observational and retrospective study in which we include patients with intestinal anastomosis, in elective surgery at the second level hospital from January 2007 to January 2017. RESULTS: 64 patients were included in the study, in which 7 presented anastomotic leakage. The statistically significant risk factors associated with anastomotic leakage were, cocaine use (p = 0.030), neoplasia as a primary pathology (p = 0.008), neoadjuvant treatment for neoplasia (p = 0.003), and end-to-end anastomosis (p = 0.037). Patients with a leakage had a longer hospital stay and a mortality of 14.3%. CONCLUSIONS: The risk factors associated with the presence of anastomotic leakage found in this study are consistent with the reported worldwide literature. However, in our results, it is worth highlighting the use of cocaine as a risk factor, with statistical significance.

ANTECEDENTES: La fuga de una anastomosis intestinal es la complicación quirúrgica más temida de la cirugía digestiva y se asocia con un aumento significativo de la morbimortalidad y de la estancia hospitalaria. OBJETIVO: Analizar los factores de riesgo asociados a la fuga de anastomosis intestinal en cirugía electiva. MÉTODO: Estudio observacional y retrospectivo en el que se recabaron los expedientes de los pacientes operados de anastomosis intestinal en forma electiva en un hospital de segundo nivel de enero de 2007 a enero de 2017. RESULTADOS: Se incluyeron 64 pacientes, de los cuales siete presentaron fuga de la anastomosis. Los factores de riesgo asociados a fuga anastomótica estadísticamente significativos fueron consumo de cocaína (p = 0.030), neoplasia como patología primaria (p = 0.008), tratamiento con neoadyuvantes para neoplasia (p = 0.003) y anastomosis término-terminal (p = 0.037). Los pacientes con fuga tuvieron una estancia intrahospitalaria más prolongada y una mortalidad del 14.3%. CONCLUSIONES: Los factores de riesgo asociados con la presencia de fuga anastomótica encontrados en este estudio son consistentes con los reportados en la literatura mundial. Sin embargo, en nuestros resultados cabe destacar el uso de cocaína como factor de riesgo, con significancia estadística.

Surgical outcome of jejunum-jejunum intussusception secondary to Rapunzel syndrome: a case report.

BACKGROUND: Adult intestinal intussusception is a rare condition caused by the mechanical disruption of bowel motility. A bezoar is defined as indigestible material inside the gastrointestinal tract that develops into a trapped mass; the most frequent bezoar is a trichobezoar. When a trichobezoar extends into the small intestine it is defined as Rapunzel's syndrome. Literature describing complications related to this pathology remains scarce. CASE PRESENTATION: A 16-year-old Mexican girl presented to our emergency room with acute abdomen and a presumptive diagnosis of intestinal obstruction. Computed tomography was suggestive of intussusception. Surgery confirmed a jejunal-jejunal intussusception with a mass within the gastric cavity extending into her small intestine, corresponding to a trichobezoar. A manual intussusception reduction and a gastrotomy with extraction of the trichobezoar were performed. CONCLUSIONS: We present a case of a jejunum intussusception as a complication of Rapunzel syndrome. Our patient had a favorable outcome after surgical intervention with a manual intussusception reduction, with retrograde displacement of the trichobezoar into the gastric lumen, and a complete extraction through a gastrostomy. Follow-up included psychiatric evaluation.

Comparison of Disposable Goldmann Applanation Tonometer, ICare ic100, and Tonopen XL to Standards of Care Goldmann Nondisposable Applanation Tonometer for Measuring Intraocular Pressure.

PURPOSE: To compare intraocular pressure (IOP) measurements by Goldmann applanation tonometer (GAT), disposable Goldmann applanation prism, ICare, and Tonopen. MATERIALS AND METHODS: A total of 74 patients with varying glaucoma status were examined in our outpatient clinic and IOP was measured with 3 tonometers. The disposable Tonojet prism (dGAT), Tonopen XL, and ICare ic100 were compared with the GAT. RESULTS: There were good intraclass correlation coefficients between IOP measurements by GAT and dGAT (0.95), Tonopen (0.83), and ICare (0.77), all P<0.001. The IOP mean differences between dGAT and GAT were mean 0.80 mm Hg; 95% limits of agreement: -3.35 to 4.96 mm Hg. For Tonopen and GAT: mean, -1.67 mm Hg; limits of agreement, -8.55 to 5.21 mm Hg. For ICare and GAT: mean, 0.44 mm Hg; limits of agreement, -8.18 to 9.06 mm Hg. CONCLUSIONS: The most reliable modality, with good correlation with the Goldmann tonometer values, was the GAT with dGAT, followed in descending order by the Tonopen XL and ICare. There was good interdevice agreement and consistency between all devices. On subgroup analysis, all 3 modalities were found to be less reliable at extreme IOP values (<10 and >24 mm Hg). These disposable modalities should be avoided in extreme IOP ranges outside the normal range.

An elderly patient's complete response to steroid therapy for collagenous gastritis.

An 85-year-old woman presented with 9.1 kg (20 lb) weight loss over 5 months and an acute onset crampy abdominal pain. Examination revealed a diffusely tender abdomen, with gastric wall thickening noted on CT scan. Upper endoscopy showed diffuse severe erythema and friability. Histologic examination with hematoxylin and eosin staining revealed collagenous gastritis characterized by active chronic inflammation with sub-epithelial collagen deposition and erosion. The patient was started on steroid therapy with rapid clinical improvement and tapered off over 2.5 months. At 6 months, the patient reported an improved appetite with resolution of her abdominal pain. Repeat endoscopy revealed a grossly normal stomach and normal mucosal biopsies. She remains without complaints 1 year later. Collagenous gastritis, rare in the elderly, is a histologic diagnosis characterized by the deposition of a sub-epithelial collagen band thicker than 10 µm with an inflammatory infiltrate. In all ages the mucosa typically appears nodular and erythematous, caused by an uneven inflammation in the surrounding depressed mucosa with atrophic changes. Specific therapy has not been well-established, and the prognosis and potential for endoscopic or histological resolution remains unclear. While anecdotal, the success of steroids may offer a reasonable starting point for treatment of similar cases.

[Comparative analysis of diagnostic scales of acute appendicitis: Alvarado, RIPASA and AIR]. / ARTÍCULO ORIGINAL Análisis comparativo de escalas diagnósticas de apendicitis aguda: Alvarado, RIPASA y AIR.

INTRODUCTION: Acute appendicitis is the most common surgical disease in emergency surgery, however, it remains a diagnostic problem and represents a challenge despite the experience and the different clinical and paraclinical diagnostic methods. OBJECTIVE: To evaluate in a comparative way the scale of Alvarado, AIR and RIPASA to determine which one is best as a diagnostic test of acute appendicitis in our population in order to arrive to an accurate diagnosis in the shortest possible time and cost. METHOD: Observational, prospective, transversal and comparative study of 137 patients to whom the scale of Alvarado, AIR and RIPASA was applied, who entered the emergency service of the Civil Hospital of Culiacán (México) with abdominal pain syndrome suggestive of acute appendicitis. RESULTS: The Alvarado scale presented sensitivity 97.2% and specificity of 27.6%. AIR presented sensitivity of 81.9% and specificity of 89.5%. RIPASA showed the same results as Alvarado. All tests showed diagnostic accuracy above 80. CONCLUSIONS: Alvarado and RIPASA presented good sensitivity, however, AIR is more specific, and has better accuracy for the diagnosis of acute appendicitis, making a better screening and thus reducing unnecessary surgeries. Therefore, it is recommended to use more AIR than Alvarado and RIPASA.

INTRODUCCIÓN: La apendicitis aguda es la enfermedad quirúrgica más común en cirugía de urgencia; sin embargo, sigue siendo un problema diagnóstico y representa un reto a pesar de la experiencia y los diferentes métodos de diagnóstico clínicos y paraclínicos. OBJETIVO: Evaluar en forma comparativa las escalas de Alvarado, AIR y RIPASA para determinar cuál es superior como prueba diagnóstica de apendicitis aguda en nuestra población, llegando a un diagnóstico preciso en el menor tiempo y costo posibles. MÉTODO: Estudio observacional, prospectivo, transversal y comparativo de 137 pacientes a quienes se aplicó las escalas de Alvarado, AIR y RIPASA, que ingresaron al servicio de urgencias del Hospital Civil de Culiacán (México) con síndrome doloroso abdominal sugestivo de apendicitis aguda. RESULTADOS: La escala de Alvarado presentó una sensibilidad del 97.2% y una especificidad del 27.6%. AIR tuvo una sensibilidad del 81.9% y una especificidad del 89.5%. RIPASA arrojó los mismos resultados que Alvarado. Todas las pruebas tuvieron una exactitud diagnóstica por arriba del 80. CONCLUSIONES: Alvarado y RIPASA presentaron buena sensibilidad, mientras que AIR es más específica y tiene mayor exactitud diagnóstica de apendicitis aguda, realizando un mejor tamizaje y permitiendo disminuir las cirugías innecesarias, por lo que se recomienda usar más AIR que Alvarado y RIPASA.

Point-of-Care ß-Lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation.

Background: ß-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point of care. Methods: We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at 3 hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving nonpreferred therapy due to severity of their reported allergy. The primary outcome was the proportion of patients receiving the preferred ß-lactam therapy. Results: Of 827 patients with reported ß-lactam allergy over 15 months, ß-lactam therapy was preferred among 632 (76%). During baseline periods, 50% (124/246) received preferred ß-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (P = .02), which improved further to 81% (313/386) upon provision of BLAST (P < .001) without any increase in incidence of adverse drug reactions (4% vs 3%; P = .4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred ß-lactam therapy (95% confidence interval, 2.4-8.2; P < .0001). Conclusions: The use of BLAST at the point of care across 3 hospital ASPs resulted in greater use of preferred ß-lactam therapy without increasing the risk of adverse drug reactions. Longer-term studies are needed to better assess the safety and clinical impact of this ASP intervention.

Intravenous administration of Reolysin, a live replication competent RNA virus is safe in patients with advanced solid tumors.

BACKGROUND: Reolysin is reovirus serotype 3-Dearing strain, a double-stranded replication-competent RNA non-enveloped icosahedral virus. It induces cytopathic and anti-cancer effects in cells with an activated ras pathway due to inhibition of the dsRNA-activated protein kinase. METHODS: This was a single center dose escalation trial of Reolysin administered intravenously every 4 weeks in doses ranging from 1 x 10(8) to 3 x 10(10) tissue culture infective dose (TCID)(50). Serum for neutralizing antibody, and serum, stool, saliva, and urine for viral shedding were collected. Tumor samples were analyzed for activating mutations in the ras and braf oncogenes. RESULTS: Eighteen patients received 27 doses of Reolysin in 6 dose cohorts accomplishing a 300 fold dose escalation without a protocol-defined dose limiting toxicity. Drug related grade 2 toxicities included fatigue and fever (1 patient each). All patients developed neutralizing antibody during the course of the study. Viral shedding was observed in 6 patients. One patient with anthracycline and taxane refractory breast cancer experienced a partial response (PR) and her tumor had a ras G12A mutation. Biopsy from her chest wall mass showed evidence of necrosis and viral replication by electron microscopy. Overall clinical benefit (1 PR + 7 stable disease) rate was 45%, and appeared higher in patients with viral shedding (67%) than those without (33%). CONCLUSION: Reolysin administered monthly as a one-hour infusion is safe and well-tolerated even in multiple doses. Reolysin has anti-tumor activity as a single agent warranting further evaluation, including in combination with chemotherapy. Viral shedding may suggest intrapatient replication yielding a benefit and should be studied carefully in future studies.

Essential role for macrophage migration inhibitory factor in gastritis induced by Helicobacter pylori.

Macrophage migration inhibitory factor (MIF) is an upstream regulator of immune and inflammatory responses; however, its role in Helicobacter pylori (HP)-associated gastritis remains unknown. We infected MIF knockout (KO) and wild-type mice with SS1 HP and found that 2 weeks after infection, MIF and its receptor CD74 were markedly up-regulated in wild-type mice. This up-regulation preceded the up-regulation of both tumor necrosis factor-alpha and intercellular adhesion molecule-1, as well as the development of moderate gastritis at 8 weeks, as determined by a significant infiltration of neutrophils, T cells, and macrophages. In contrast, KO mice were protected against HP-induced gastritis by preventing the up-regulation of CD74 and Th1-mediated immune injury, including a reduction in the Th1 transcriptional factor T-bet and the expression of interferon-gamma. Additionally, inhibition of skin delayed type hypersensitivity reactions to HP antigens in KO mice also suggested a critical role for MIF in cell-mediated injury. A regulatory role for MIF in Th1-immune responses was further demonstrated by the finding that antigen-primed CD4(+) T cells lacking MIF failed to differentiate into the Th1 phenotype; these cells were instead promoted to Th2 differentiation after challenge with HP antigen in vitro. Results from this study indicated that inhibition of HP-induced innate immune responses and Th1-mediated immune injury may be the key mechanisms by which KO mice failed to develop gastritis after HP infection.

Loss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivo.

Ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma) possess anticancer properties. However, the efficacy of PPAR gamma ligands varies in different cancers. In colon cancer, the role of PPAR gamma and its ligands is controversial. We recently showed that downregulation of X-linked inhibitor of apoptosis protein (XIAP) could sensitize colon cancer cells to troglitazone, and 15-deoxy-D12,14-prostaglandin J2 (15-PGJ2) induced cell killing. In our study, we aimed to examine whether rosiglitazone, another more clinically relevant PPAR gamma ligand, has any synergistic anticancer effect with XIAP downregulation in colon cancer. Human colon cancer cell lines HCT116-XIAP(+/+) cells and HCT116-XIAP(-/-) cells were treated with various concentrations of rosiglitazone. The effects of rosiglitazone on cell proliferation, apoptosis and growth of xenograft colon cancers were studied. Rosiglitazone barely suppressed the growth and only very weakly induced apoptosis in HCT116 cells in vitro. Loss of XIAP did not sensitize HCT116 cells to rosiglitazone-induced growth inhibition or apoptosis. In vivo studies revealed that rosiglitazone strongly suppressed the growth of xenograft colon cancer, especially tumors derived from HCT116-XIAP(-/-) cells. The rosiglitazone-treated tumor had reduced expression of ki-67 and lowered mitotic rate. Downregulation of XIAP was associated with an impaired activation of PPAR gamma by its ligand. Rosiglitazone induced marked upregulation of PTEN in HCT116-XIAP(-/-) cells, as well as in xenograft tumors derived from HCT116-XIAP(-/-) cells. We concluded that rosiglitazone significantly suppresses the growth of xenograft colon cancer, and downregulation of XIAP sensitizes the xenograft tumors to rosiglitazone-induced tumor suppression in vivo via upregulation of PTEN.

A phase I safety and dose escalation trial of docetaxel combined with GEM231, a second generation antisense oligonucleotide targeting protein kinase A R1alpha in patients with advanced solid cancers.

PURPOSE: GEM231 is a second-generation antisense oligonucleotide targeting the mRNA of the R1alpha regulatory subunit of cAMP dependent protein kinase A. Preclinical studies have demonstrated synergistic antitumor activity when GEM231 is combined with docetaxel. This trial assesses the safety of this combination. EXPERIMENTAL DESIGN: Docetaxel was administered once every three weeks (one-cycle) at doses between 50-75 mg/m2. GEM231 was administered twice weekly at 220 mg/m2 for 3 (schedule-A), or 2 (schedule-B) weeks. RESULTS: Twenty patients with chemotherapy-refractory advanced cancer received a total of 39 cycles of therapy. Six patients in schedule-A received docetaxel 50 mg/m2, and 14 patients in schedule-B received docetaxel 50-75 mg/m2. In schedule-A, 2 of 6 patients developed cycle-1 dose limiting toxicity (DLT)-grade-3 fatigue or grade-3 serum transaminase elevation. In schedule-B, 1 of 4 patients developed cycle-1 DLT at the highest dose of docetaxel tested (75 mg/m2)--grade-3 febrile neutropenia. Subsequent dose escalations were not pursued since the overall incidence of grade-3 toxicities (including those that occurred after cycle 1) was 75%, and this dose was close to the single agent MTD of docetaxel. Grade-3 toxicities included fatigue (2 patients), transaminase elevation (4 patients), and altered mentation (1 patient). The mean post-infusion aPTT was significantly higher than the pre-infusion value [14.8 seconds; p<0.001]; however, there were no hemorrhagic episodes. CONCLUSIONS: The recommended dose for further development of the combination of docetaxel and GEM231 is 75 mg/m2 and 220 mg/m2, respectively. It is important to administer GEM231 twice weekly for 2 consecutive weeks followed by a one-week break.