IL-33/sST2 signaling pathway in pulmonary thromboembolism: A clinical observational study.

BACKGROUND: Pulmonary thromboembolism (PTE) is a cardiovascular emergency that can result in mortality. In the interleukin-33 (IL-33) /soluble suppression of tumorigenicity 2 (sST2) signaling pathway, increased sST2 is a cardiovascular risk factor. This study aimed to investigate the effectiveness of biomarkers in the IL-33/sST2 signaling pathway in determining PTE diagnosis, clinical severity, and mortality. METHOD: This study was conducted as a single-center, prospective, observational study. Patients admitted to the emergency department and diagnosed with PTE constituted the patient group (n = 112), and healthy volunteers with similar sociodemographic characteristics constituted the control group (n = 62). Biomarkers in the IL-33/sST2 signaling pathway were evaluated for diagnosis, clinical severity, and prognosis. RESULTS: IL-33 was lower in the patient group than in the control group (275.89 versus 403.35 pg/mL), while sST2 levels were higher in the patient group than in the control group (53.16 versus 11.78 ng/mL) (p < 0.001 and p = 0.001; respectively). The AUC of IL-33 to diagnose PTE was 0.656 (95 % CI: 0.580-0.726). The optimal IL-33 cut-off point to diagnose PTE was ≤304.11 pg/mL (56.2 % sensitivity, 79 % specificity). The AUC of sST2 to diagnose PTE was 0.818 (95 % CI: 0.752-0.872). The optimal sST2 cut-off point to diagnose PTE was >14.48 ng/mL (83 % sensitivity, 71 % specificity). IL-33 levels were lower in patients with mortality (169.85 versus 332.04 pg/mL) compared to patients without mortality, whereas sST2 levels were higher in patients with mortality (118.32 versus 28.07 ng/mL) compared to patients without mortality (p > 0.001 for both). The AUC of IL-33 to predict the mortality of PTE was 0.801 (95 % CI: 0.715-0.870). The optimal IL-33 cut-off point to predict the mortality of PTE was ≤212.05 pg/mL (75 % sensitivity, 79.5 % specificity). The AUC of sST2 to predict the mortality of PTE was 0.824 (95 % CI: 0.740-0.889). The optimal sST2 cut-off point to predict the mortality of PTE was >81 ng/mL (95.8 % sensitivity, 78.4 % specificity). CONCLUSION: In the IL-33/ST2 signaling pathway, decreased IL-33 and increased sST2 are valuable biomarkers for diagnosis and prediction of mortality in patients with PTE.

In Vitro efficacy of cyclosporine a and various antiseptics and antiviral drugs on adenovirus genotype 8, a common cause of epidemic keratoconjunctivitis.

PURPOSE: To evaluate the in vitro efficacy of cidofovir, ganciclovir, povidone-iodine, chlorhexidine, and cyclosporine A on adenovirus genotype 8. METHODS: Conjunctival samples were collected from patients with adenoviral conjunctivitis and cultured in A549 cells. Adenovirus diagnosis was confirmed by RT-PCR. For each drug, the 50% cytotoxic concentration (CC 50 ) was determined. Subsequently, the antiviral activity was tested at concentrations below CC 50, and the 50% inhibitor concentration (IC 50 ) of drugs was determined RESULTS: While the IC 50 of cidofovir against adenovirus genotype 8 was 3.07 ± 0.8 µM, ganciclovir, povidone-iodine, chlorhexidine, and cyclosporine A were not found to be effective against adenovirus genotype 8 at concentrations below the CC 50 value. CONCLUSIONS: Cidofovir was found effective and the IC 50 value was within the ranges in the literature. Ganciclovir and cyclosporine A were found to be ineffective at doses below the cytotoxic dose, povidone-iodine and chlorhexidine was found to be highly cytotoxic.

Effect of Nitrogen, Air, and Oxygen on the Kinetic Stability of NAD(P)H Oxidase Exposed to a Gas-Liquid Interface.

Biocatalytic oxidation is an interesting prospect for the selective synthesis of active pharmaceutical intermediates. Bubbling air or oxygen is considered as an efficient method to increase the gas-liquid interface and thereby enhance oxygen transfer. However, the enzyme is deactivated in this process and needs to be further studied and understood to accelerate the implementation of oxidative biocatalysis in larger production processes. This paper reports data on the stability of NAD(P)H oxidase (NOX) when exposed to different gas-liquid interfaces introduced by N2 (0% oxygen), air (21% oxygen), and O2 (100% oxygen) in a bubble column. A pH increase was observed during gas bubbling, with the highest increase occurring under air bubbling from 6.28 to 7.40 after 60 h at a gas flow rate of 0.15 L min-1. The kinetic stability of NOX was studied under N2, air, and O2 bubbling by measuring the residual activity, the deactivation constants (kd1) were 0.2972, 0.0244, and 0.0346 with the corresponding half-lives of 2.2, 28.6, and 20.2 h, respectively. A decrease in protein concentration of the NOX solution was also observed and was attributed to likely enzyme aggregation at the gas-liquid interface. Most aggregation occurred at the air-water interface and decreased greatly from 100 to 14.16% after 60 h of bubbling air. Furthermore, the effect of the gas-liquid interface and the dissolved gas on the NOX deactivation process was also studied by bubbling N2 and O2 alternately. It was found that the N2-water interface and O2-water interface both had minor effects on the protein concentration decrease compared with the air-water interface, whilst the dissolved N2 in water caused serious deactivation of NOX. This was attributed not only to the NOX unfolding and aggregation at the interface but also to the N2 occupying the oxygen channel of the enzyme and the resultant inaccessibility of dissolved O2 to the active site of NOX. These results shed light on the enzyme deactivation process and might further inspire bioreactor operation and enzyme engineering to improve biocatalyst performance.

The Relationship between Clinical Findings and Viral Load in Adenoviral Keratoconjunctivitis.

The aim of this study was to evaluate the relationship between clinical findings and viral load in adenoviral keratoconjunctivitis (Ad-Kc). In this cross-sectional study, 30 eyes of 30 patients with Ad-Kc were assessed. Real-time polymerase chain reaction was performed to detect and quantify adenovirus in all samples. Patients were divided into three subgroups according to baseline viral load (<107, 107-108, >108 human adenovirus [HAdV] copies/mL). The duration of follow-up, HAdV DNA copy number, treatment regimen, and detailed clinical findings, including uncorrected visual acuity, eyelid edema, conjunctival hyperemia, chemosis, follicular reaction, corneal involvement, conjunctival pseudomembrane, and subepithelial infiltrates (SEIs) were recorded. This study showed that a high initial viral load was associated with the development of SEIs and pseudomembrane formation (P < 0.05). The clinical findings and ocular complications of Ad-Kc were similar in the treatment groups at the final examination (P > 0.05). Our results show that a high initial viral load in Ad-Kc may be predictive of inflammatory sequelae. Determining the initial viral load in Ad-Kc may help understand the clinical course of the disease better and prevent complications.

Improved contact lens fitting after corneal cross-linking in eyes with progressive keratoconus.

OBJECTIVES: The study aimed to assess the possible effects of corneal cross-linking (CXL) on contact lens (CL) fitting in patients with progressive keratoconus who initially had CL intolerance. METHODS: A retrospective review was performed of the medical records of patients who had stopped CL wear due to discomfort prior to CXL and who were fitted with CLs after CXL. All eyes were evaluated pre- and 1, 6, 12, 24 months postoperatively. Data collected included pre- and post-CXL refraction, corneal topographic data, uncorrected visual acuity, and best-corrected visual acuity (BCVA). CL comfort was evaluatedusing theLikert scale post-CXL. RESULTS: A total of 20 eyes from 14 patients were included in the study. Preoperative Kmax values significantly decreased by 2.8 D at 6 months and by 4.1 D at 12 months after CXL (p < 0.001 for both). CLs were prescribed on average 12 ± 2.5 months after CXL. The mean duration of successful CL wear was 10.4 ± 2.8 months during the follow-up period. Subjective CL comfort scores were satisfactory post-CXL. CONCLUSION: CXL not only halts the progression of keratoconus but may also improve CL tolerance by providing a more regular shaped cornea in these patients. Ongoing corneal topographic changes in the late postoperative period after CXL may have a positive effect on CL fitting.

In Vitro Efficacy of Chlorhexidine and a riboflavin/UVA Combination on Fungal Agents of Keratitis.

Purpose: Mycotic keratitis is a global ophthalmological problem because it is difficult to diagnose and treat. The aim of the current study was to evaluate the efficiency of using antifungal agents amphotericin B (AMB), voriconazole (VRC), 0.02% chlorhexidine (CHX), and a combination of riboflavin and UVA treatment against two fungal genera (Aspergillus and Fusarium) responsible for keratitis.Methods: We evaluated antifungal efficiencies of riboflavin/UVA and the antifungal drugs VRC, AMB, and CHX (alone and in combination) against fungal inocula at four concentrations. We recorded colony counts of isolates for Aspergillus terreus, A. flavus, A. fumigatus, Fusarium falciforme, F. proliferatum, and F. solani on Mueller-Hinton agar plates.Results: Fungal suspensions exposed to the following treatment combinations did not allow fungal growth: riboflavin/UVA and VRC, riboflavin/UVA and AMB, riboflavin/UVA and CHX, and CHX alone. We observed a statistically significant reduction (P < .05) in the number of colonies on agar plates when fungal suspensions were treated with riboflavin/UVA, VRC, and AMB only.Conclusions: Riboflavin/UVA treatment in combination with AMB, VRC, and CHX are capable of killing keratitis-inducing fungi (P < .05). The antiseptic CHX exerted a considerable antifungal effect on all strains we examined. Therefore, we recommend CHX as additional therapy against mycotic keratitis, particularly when keratitis is caused by multi-resistant members of Fusarium.

Atypical herpes simplex keratitis: frequency, clinical presentations and treatment results.

AIMS: To determine herpes simplex virus (HSV) DNA positivity in corneal scraping samples obtained from patients with microbial keratitis whose findings were not specific for HSV keratitis and to evaluate these particular cases with respect to clinical features and antiviral treatment results. METHODS: Records of patients with microbial keratitis treated in a tertiary eye care hospital within the 3-year period were evaluated retrospectively. Real-time polymerase chain reaction (PCR) was used to identify HSV DNA. Smear slides were evaluated by light microscopy. Patients with typical presentations and histories of HSV keratitis were excluded. RESULTS: Two hundred and seventy-six eyes of 276 patients were included in the study. HSV-1 DNA was detected in 25 eyes (9%). In these 25 eyes, the initial diagnosis was fungal or bacterial keratitis. The mean symptom duration was 20 ± 14 days (2-60 days). The risk factors were ocular surgery (20%), blepharitis (16%), trauma (8%) and contact lens wear (4%); however, the majority of patients did not have any specific cause for keratitis (52%). Clinical features were variable and not typical for any particular etiology. Culture and microscopic examinations revealed bacteria and/or fungi in 6 patients in addition to herpes infection. Antiviral treatment was successful in 72% of patients. CONCLUSION: Herpetic corneal infections can present without typical dendritic or geographic ulcers and may be masked by other infections. Real-time PCR is a useful method for rapid and definitive diagnosis. HSV infection should be considered for microbial keratitis without specific risk factors, with negative culture results and poor response to antimicrobial agents.

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis.

PURPOSE: To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis. DESIGN: Retrospective case series in a tertiary university hospital. PARTICIPANTS: CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment. METHODS: The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery. MAIN OUTCOME MEASURES: Grade of the corneal infection. RESULTS: Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20-74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15-40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05). CONCLUSIONS: The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

Aspergillus flavus Keratitis: Experience of a Tertiary Eye Clinic in Turkey.

We investigated the clinical and mycological characteristics of four cases of mycotic keratitis caused by Aspergillus flavus that occurred from July 2014 to May 2015 at Çukurova University Hospital, Adana, Turkey. In a 10-month period, a total of 64 corneal smear/scrapings were examined from patients with suspected mycotic keratitis. Fungal cultures were positive in six of these patients, indicating a 9.4% incidence of mycotic keratitis in this region, including four cases of A. flavus and two cases of Fusarium spp. The predisposing factors, clinical presentation, and success of the therapeutic approaches were further evaluated. For all cases, topical voriconazole was the first choice of treatment. Surgical procedures were required to control infection in 3 of the 4 cases, including intrastromal voriconazole injection for two cases and keratoplasty for one case. Predisposing factors included trauma (two cases, 50%), contact lens use (one case, 25%), and previous ocular surgery (one case, 25%). The clinical presentations also differed, including a well-limited ulcer (one case), an ulcer with an irregular feathery margin (one case), and ulcers with satellite lesions (two cases). The mean duration between the time of presentation and definitive diagnosis by culture was 14 days (8-25 days). We observed that A. flavus keratitis can present with different underlying factors and clinical conditions. A combination of antifungal therapy and supportive surgical intervention may resolve infections caused by A. flavus in the cornea.

Aspergillus terreus infection in a sutureless self-sealing incision made during cataract surgery.

Here, we describe a case of keratitis caused by Aspergillus terreus in an 80-year-old immunocompetent woman 1 month after uneventful cataract surgery. The patient presented with decreased visual acuity (20/50) and severe pain in her right eye. Examination revealed a 3.5 × 4.5 mm white-colored deep stromal infiltration located on the temporal corneal tunnel incision. Corneal scraping samples were obtained for cytological and culture examinations. The cinnamon-brown colonies consisting of a dense felt of conidiophores were identified as A. terreus using molecular data. Using CLSI M38-A2 microdilution method, minimum inhibitory concentration values of amphotericin B, itraconazole, voriconazole, and posaconazole were determined to be 2, 1, 0.25, and 1 µg/ml, respectively, and minimum effective concentration values of caspofungin and anidulafungin were ≤0.03 and ≤0.03, respectively, at 48 h for the A. terreus strain. Antifungal therapy was started as topical 1 % voriconazole drops hourly and 5 % natamycin ointment five times a day; however, corneal infection and melting progressed despite the ongoing intensive treatment and visual acuity dropped to the 20/200 level at the end of the first week. Amniotic membrane transplantation was performed to promote corneal healing. Topical medication was tapered and discontinued within 2 months based on the clinical features. The ulcer healed with scarring and vascularization, and visual acuity improved to 20/50. In conclusion, A. terreus is a very uncommon cause of mycotic keratitis and is especially rare after cataract surgery. We suggest that early and accurate diagnosis and appropriate treatment of A. terreus keratitis may have a major impact on preventing severe disease complications.

Surgical rehabilitation following ocular chemical injury.

PURPOSE: The purpose of this study is to evaluate the management of limbal stem cell deficiency (LSCD) secondary to chemical ocular burns. MATERIALS AND METHODS: The charts of 48 eyes of 40 patients with grade 2 or higher chemical injury were evaluated retrospectively. Subjects with follow-up longer than 1 year were included. Medical treatment, surgical correction of abnormalities of ocular adnexial structures, limbal stem cell transplantation from patient's fellow eye, from living relatives or from cadaveric donor, amniotic membrane transplantation, conjunctival epitheliectomy, chelation with ethylenediaminetetraacetic acid and penetrating keratoplasty were the treatment modalities. Outcome measures were ocular surface stability and corrected distance visual acuity (CDVA). Failure was defined as the appearance of persistent epithelial defect (nonhealing epithelial defect for more than 2 weeks) with progressive corneal conjunctivalization/vascularization and thinning, and also progression of conjunctivalization to the central 6 mm of the cornea in eyes with subsequent keratoplasty. RESULTS: The mean age of 31 male and 9 female patients were 32.32 ± 12.6 years. LSCD was bilateral in 8 cases. The mean follow-up was 77.2 ± 35.1 months. The presentations were in acute phase in 37.5%, in subacute phase in 32.5% and in chronic phase in 30% of the patients. Only 13 of 48 (27.1%) eyes obtained sufficient ocular surface stability through medical treatment; however, only 5 of these eyes achieved CDVA of less than 0.7 logMAR. Limbal stem cell transplantation was performed in 26 eyes as conjunctival limbal autograft, living-related conjunctival limbal allograft and keratolimbal allograft or as a combination of these transplantations. At the last visit, 30 eyes (62.5%) had an intact and stable ocular surface. Clear cornea was achieved in 11 (78.6%) of 14 eyes with grade 2 injury, in 9 (60%) of 15 eyes with grade 3 injury, in 5 (50%) of 10 eyes with grade 4 injury, in 1 (16.6%) of 6 eyes with grade 5 injury and in 1 (33.3%) of 3 eyes with grade 6 injury. The CDVA that was 1.66 ± 0.99 logMAR initially improved to 0.87 ± 0.85 logMAR at the last visit (p < 0.001). CONCLUSION: While patients with low-grade chemical injury seem to benefit quite well from the medical treatment, amniotic membrane transplantation, limbal graft transplantation and subsequent keratoplasty; patients with severe injuries seem to be more prone to failure after all of the available treatment modalities.

Human placental macrophages (Hofbauer cells) in severe preeclampsia complicated by HELLP syndrome: immunohistochemistry of chorionic villi.

OBJECTIVE: To evaluate Hofbauer cells in the placentas of women diagnosed with HELLP syndrome. STUDY DESIGN: The present study compared 20 patients with HELLP syndrome and 20 control patients with respect to demographics, hematological parameters and the presence of Hofbauer cells in placental samples. CD-68 antibody was used for immunohistochemical examination. The total number and size of Hofbauer cells were measured in the placental villi, and the proportion of Hofbauer cells relative to the vascular structure was also compared between groups. RESULT: The patient and control groups were similar according to baseline obstetric characteristics. White blood cell counts in patients with HELLP syndrome and the control group were 15,139 +/- 4,169 and 10,806 +/- 2,888, respectively, and were significantly increased among patients with HELLP syndrome (p < 0.001). Hofbauer cell numbers in the placental villi of patients with HELLP syndrome were significantly elevated in comparison to normotensive controls (p = 0.046). The proportion of Hofbauer cells in the placental villi according to proximity to the vascular structure were 3.85 +/- 1.66 in the HELLP group and 1.75 +/- 1.12 in controls (p < 0.001). Sizes of the Hofbauer cells were not statistically different between groups. CONCLUSION: Increased Hofbauer cells may be associated with increased inflammation or may have an adaptive mechanism at the fetal site of the placenta in patients with HELLP syndrome.

An unexpected delayed complication of cataract surgery: retinal detachment secondary to capsular tension ring dislocation.

We aim to present a case of retinal detachment secondary to capsular tension ring dislocation following cataract surgery. A 45-year-old man who underwent cataract surgery 2 years previously presented with decreased vision in his left eye. The patient's posterior capsule was intact with a well-located posterior chamber intraocular lens. Fundus examination revealed retinal detachment with retinal tears, and a capsular tension ring located around the tear was noticed during pars plana vitrectomy; it was removed through the sclerotomy site. In conclusion, dislocation of the capsular tension ring is a rare and unexpected complication of cataract surgery. Although the integrity of the posterior lens capsule is partially preserved, the ring may shift through a small tear in the bag even during its placement, and may cause retinal tears, retinal detachment or just remain silently suspended in the vitreous.