Extracorporeal liver support techniques: a comparison.

ExtraCorporeal Liver Support (ECLS) systems were developed with the aim of supporting the liver in its detoxification function by clearing the blood from hepatic toxic molecules. We conducted a retrospective comparative analysis on patients presenting with liver failure who were treated with different extracorporeal techniques in our intensive care unit to evaluate and compare their detoxification abilities. To verify the effectiveness of the techniques, mass balance (MB) and adsorption per hour were calculated for total bilirubin (TB), direct bilirubin (DB), and bile acids (BA) from the concentrations measured. MB represents the total amount (mg or mcMol) of a molecule removed from a solution and is the only representative parameter to verify the purification effectiveness of one system as it is not affected by the continuous production of the molecules, released in the circulation from the tissues, as it is the case for the reduction rate (RR). The total adsorption per hour is calculated by the ratio between MB and the time duration and shows the adsorption ability in an hour. Our comparative study shows the superior adsorption capability of CytoSorb system regarding TB, DB, and BA, evaluated through the MB and adsorption per hour, in comparison with CPFA, MARS, Prometheus, and PAP. In conclusion, as extracorporeal purification in liver failure could be considered useful for therapeutic purposes, Cytosorb, being more performing than other systems considered, could represent the device of first choice.

The changing pattern of bacterial and fungal respiratory isolates in patients with and without COVID-19 admitted to intensive care unit.

OBJECTIVES: Severe acute respiratory syndrome 2 (SARS-CoV-2) pandemic has had a heavy impact on national health system, especially in the first wave. That impact hit principally the intensive care units (ICUs). The large number of patients requiring hospitalization in ICUs lead to a complete upheaval of intensive wards. The increase in bed, the fewer number of nurses per patient, the constant use of personal protective equipment, the new antimicrobial surveillance protocols could have had deeply effects on microbiological flora of these wards. Moreover, the overconsumption of antimicrobial therapy in COVID-19 patients, like several studies report, could have impact of this aspect. Aim of this study is to evaluate the changing pattern of microbiological respiratory isolates during and before COVID-19 pandemic in a tertiary hospital ICUs. METHODS: A retrospective, observational study was conducted in ICUs of "ASST Papa Giovanni XXIII", a large tertiary referral hospital in Northern Italy. We have retrospectively collected the microbiological data from bronchoalveolar lavage (BAL) and tracheal aspirate (TA) of patients with COVID-19, hospitalized in ICUs from 22nd February 2020 to 31st May 2020 (Period 1), and without COVID-19, from 22nd February 2019 to 31st May 2019 (Period 2). We compared the prevalence and the antibiotic profile of bacterial and fungal species in the two time periods. RESULTS: The prevalence of Pseudomonas spp. shows a statistically significant increase from patients without COVID-19 compared to COVID-19 positive as well as the prevalence of Enterococcus spp. On the contrary, the prevalence of Gram negative non fermenting bacteria (GN-NFB), Haemophilus influenzae and Streptococcus pneumoniae showed a significant reduction between two periods. There was a statistically significant increase in resistance of Pseudomonas spp. to carbapenems and piperacillin/tazobactam and Enterobacterales spp. for piperacillin/tazobactam, in COVID-19 positive patients compared to patients without COVID-19. We did not observe significant changing in fungal respiratory isolates. CONCLUSIONS: A changing pattern in prevalence and resistance profiles of bacterial and fungal species was observed during COVID-19 pandemic.

Optic nerve head diurnal vessel density variations in glaucoma and ocular hypertension measured by optical coherence tomography angiography.

BACKGROUND/AIMS: To evaluate diurnal variations in optic nerve head (ONH) vessel density assessed by optical coherence tomography angiography (OCT-A) in healthy subjects, ocular hypertension (OHT), and open-angle glaucoma (OAG) patients. METHODS: Forty subjects (OAG, 21; OHT, 6; healthy, 13) were assessed for vessel density percentage (VD%) and flow index in the ONH (NH VD%, NH index), and in the radial peripapillary capillary layer (RPC VD%, RPC index) at 9:00, 11:00, 14:00, 16:00, and 18:00 on a single day. Repeated measures ANOVAs were used to test for changes in the parameters measured at multiple time points. RESULTS: All OCT-A parameters analyzed at the different time points were statistically lower in the OAG patients compared to both the OHT and healthy groups (p < 0.05). In the OAG group, the NH index, RPC index, NH VD%, and RPC VD% were statistically lower at 18:00 compared to 14:00, and the RPC VD% was statistically lower at 9:00 than 14:00. In the OHT group, the RPC index was statistically lower at 9:00 than 11:00. In the healthy group, the NH VD% and RPC VD% were statistically lower at 16:00 than 18:00, and the RPC index was statistically lower at 9:00 than 11:00. No other statistically significant difference was found in none of the three groups comparing any other time point (p > 0.05). CONCLUSION: In healthy subjects, OHT and OAG patients, the variations in the OCT-A derived parameters were relatively small. These results suggest that in the clinical practice the OCT-A assessment can be performed independently of the time of the day, contrasting IOP evaluation.

Elevated intraocular pressure in patients with acromegaly.

PURPOSE: To evaluate central corneal thickness (CCT) and intraocular pressure (IOP) in a cohort of acromegalic patients, and to correlate CCT with serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). METHODS: Consecutive patients affected by acromegaly underwent a comprehensive endocrinological and ophthalmological evaluation, including serum GH and IGF-1 levels, CCT measured with ultrasonic pachymetry and IOP assessed with Goldmann applanation tonometry. RESULTS: Fourteen patients with acromegaly and 28 healthy controls were included in the study. Acromegalic patients had a statistically higher median CCT (570 µm [range 551.5-638] vs 542.7 µm [range 461.5-610]; p < 0.01) and higher median IOP (17.2 mm Hg [range 14-21] vs 13.7 mm Hg [range 10.5-19]; p < 0.01) than healthy controls. No statistically significant correlation was found among CCT and GH, CCT and IGF-1, IOP and GH, IOP and IGF-1 in the acromegalic group, whereas a statistically significant correlation was documented between CCT and IOP in the entire cohort (Spearman's correlation coefficient: 0.56, p < 0.01). However, when IOP was corrected for CCT no significant difference was found between the two study groups (p = 0.07). CONCLUSIONS: Our results suggest that acromegaly is associated with an increased CCT, which could lead to an overestimation of IOP readings as determined with Goldmann applanation tonometry.

Risk factors associated with progression in exfoliative glaucoma patients.

PURPOSE: To evaluate exfoliative glaucoma (XFG) patients over 5 years, determining risk factors associated with progression or non-progression of glaucoma. METHODS: A retrospective, observational study. Patients were chosen from consecutive charts and data collected from each available visit included in the follow-up period. Data were abstracted for non-progressed XFG patients for 5 years and for progressed patients until glaucoma worsened. Progression was determined from patient records and by disc photographs. RESULTS: There were 71 (53%) progressed and 63 (47%) non-progressed XFG patients.Baseline parameters demonstrated worse visual field damage (p=0.014) and more prescribed medicines (p=0.03) in progressed patients. The mean intraocular pressure (IOP) for progressed patients was 18.7±4.3 and 17.3±3.4 mm Hg for non-progressed patients (p=0.047). The mean IOP that best separated the groups was 17 mm Hg with 60% staying non-progressed at or below this level and 30% above this level. At the last visit, progressed patients had more medicines prescribed (1.7) than non-progressed patients (1.3, p=0.005). A multivariate regression analysis showed higher mean, peak and variance of IOP, number of glaucoma medications at the final visit and presence of a disc hemorrhage (n=5) as independent risk factors for progression (p≤0.05). CONCLUSION: IOP reduction in XFG may be essential in reducing disease progression. The presence of disc hemorrhage in XFG may suggest an increased probability of progression despite treatment to within the normal IOP range.

Human recombinant nerve growth factor (Cenegermin) in a patient affected by primary congenital glaucoma with neurotrophic keratopathy.

PURPOSE: To report a case of neurotrophic keratopathy (NK) in a patient affected by primary congenital glaucoma (PCG) who undergone glaucoma drainage implant surgery. NK was successfully treated with human recombinant Nerve Growth Factor (Cenegermin) eye drops. CASE REPORT DESCRIPTION: A 46-years-old patient affected by primary congenital glaucoma underwent Ahmed glaucoma valve implantation in the right eye, after several unsuccessful surgeries to control intraocular pressure (IOP) since the age of three. Surgical intervention was performed without complications, and IOP was well-controlled post-operatively. However, 1 month after surgery, he developed NK with stromal ulceration, initially treated with a topical combination of preservative-free artificial tears and antibiotic ointment. As NK did not resolve, a new treatment with Cenegermin 20 µg/ml eye drops, 6 times daily, was started. OUTCOME: NK completely resolved after 8 weeks of Cenegermin treatment, with complete restoration of corneal integrity and improvement of corneal sensitivity and transparency. Visual acuity in the operated eye reverted to the pre-operative value. CONCLUSION: Cenegermin was extremely effective in restoring corneal integrity in this PCG patient with NK.

A new look at the safety and tolerability of prostaglandin analogue eyedrops in glaucoma and ocular hypertension.

INTRODUCTION: In the last 25 years, topical prostaglandin analogues (PGAs) have emerged to become first line and first choice therapeutic options in the management of glaucoma and ocular hypertension (OHT). Although the short-term efficacy and safety of PGAs has been extensively investigated, less is known about their long term safety and tolerability. This gap in current knowledge is clinically relevant, because treatment-related adverse events and long-term tolerability issues are key determinants of the overall success of long-term therapy and the final outcome of a lifelong, symptomless disease like glaucoma. AREAS COVERED: We include selected evidence pertaining to the safety and tolerability of available and emerging PGA formulations. We also outline PGA formulations with different concentrations of the active ingredient, different preservatives, and preservative-free (PF) options. EXPERT OPINION: Undoubtedly PGAs will continue to play a major role in the medical therapy of glaucoma and OHT. Despite extensive literature and prolonged clinical experience with these agents worldwide, a number of areas that warrant further research have been identified in the present review. Recently launched novel PGAs, or those still in development offer new opportunities and future challenges.

Physiology-Enhanced Data Analytics to Evaluate the Effect of Altitude on Intraocular Pressure and Ocular Hemodynamics.

Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.

A rare case of endophthalmitis after bleb needle revision for glaucoma Xen® gel stent.

PURPOSE: To describe the first case of endophthalmitis caused by Sphingobacterium spiritivorum, a glucose non-fermenting Gram-negative rod, in a patient previously implanted with a Xen® gel stent. CASE REPORT DESCRIPTION: An 83-year-old patient, affected by open-angle glaucoma and with a previous surgery of combined cataract extraction and Xen gel stent implantation, developed endophthalmitis 1 month after bleb needle revision with 5-fluorouracil injection. At presentation, best corrected visual acuity was hand movement, hypopyon was evident into the anterior chamber and a flat bleb with no sign of leakage was present over the Xen gel implant. OUTCOME: Immediate pars plana vitrectomy was performed, with intravitreal antibiotic administration and silicon oil tamponade. S. spiritivorum was isolated from vitreous bacterial culture. According to the antibiogram, patient was treated with topical fortified ceftazidime eyedrops and appropriate systemic antibiotics (intravenous meropenem, 500 mg every 8 h for 7 days, followed by oral cotrimoxazole, 160 + 800 mg, twice a day for 10 days). After 2 weeks of treatment, ocular inflammation was resolved, best corrected visual acuity was 0.1 (Snellen chart) and intraocular pressure was 18 mm Hg without topical hypotensive therapy. CONCLUSION: S. spiritivorum was isolated for the first time as a causative agent of endophthalmitis in humans. Bleb needle revision in patients with Xen gel implant is not free of complications, and an attentive follow-up is required.

Efficacy and Safety of PreserFlo® MicroShunt After a Failed Trabeculectomy in Eyes with Primary Open-Angle Glaucoma: A Retrospective Study.

INTRODUCTION: To evaluate the efficacy and safety of PreserFlo® MicroShunt in primary open angle glaucoma (POAG) eyes after a single failed trabeculectomy. METHODS: Retrospective review of POAG eyes with a failed trabeculectomy that underwent PreserFlo® MicroShunt implantation from March 2019 to November 2019, in two Italian glaucoma centers. Pre- and postoperative data were collected and compared. RESULTS: A total of 31 surgeries in 31 patients were reviewed. Mean preoperative IOP and mean preoperative number of medications were 24.12 ± 3.14 mmHg and 3.29 ± 0.64, respectively, and decreased to 12.56 ± 2.64 mmHg and 0.46 ± 0.77 at the 12-month postoperative follow-up visit (p < 0.01). The most frequent adverse events were transient hypotony (6 eyes, 19.3%) and choroidal effusion (3 eyes, 9.6%). In all cases spontaneous resolution was observed, with no intervention. CONCLUSION: In POAG eyes with a single failed trabeculectomy, the PreserFlo® MicroShunt was safe and effective in reducing the IOP after a 12-month follow-up. The PreserFlo® MicroShunt may represent a viable choice as a second surgery.

A Comparison of Hyper-Reflective Retinal Spot Counts in Optical Coherence Tomography Images from Glaucomatous and Healthy Eyes.

PURPOSE: To compare the number of hyper-reflective retinal spots (HRS) in optical coherence tomography (OCT) images of healthy controls and patients affected with primary open angle glaucoma (POAG). METHODS: Thirty patients affected with POAG and 34 healthy controls were recruited and underwent raster OCT examination of the macular region. Among the acquired B-scans, the one with the lowest foveal thickness was selected, and a central area of 3000 µm was defined (region of interest, ROI), in order to identify HRS. HRS were defined as small point-like hyper-reflective elements, detectable at the visual inspection of the OCT image. HRS were independently counted by two investigators in the ROI of each OCT scan. RESULTS: Inter-rater agreement for HRS counting was good to excellent (ICC = 0.96, 95% CI: 0.83-0.99). More HRS were found in the OCT images from glaucoma patients, in comparison with healthy controls (average value: 90.5 ± 13.02 and 74.72 ± 11.35, for glaucoma and healthy subjects, respectively; p < 0.01). Significant correlations between the average number of HRS and visual field mean deviation (MD, p = 0.01) and pattern standard deviation (PSD, p < 0.01) were found. CONCLUSIONS: OCT images from glaucoma patients showed a higher number of HRS when compared with healthy controls. As HRS have been hypothesized to be a sign of neuroinflammation, these results may support the role of neuroinflammation in glaucoma etiopathogenesis.

Pre-operative conjunctival flora in patients with local and/or systemic risk factors for post cataract surgery infection in Northern Italy.

PURPOSE: To investigate the pre-operative conjunctival flora in patients undergoing cataract surgery with major local and/or systemic risk factors for developing post-operative infection. METHODS: A total of 83 patients underwent bacterial culture and sensitivity testing of conjunctival swabs obtained from both eyes because of local risk factors at the pre-operative visit (i.e. chronic blepharitis, conjunctivitis, or lacrimal system disease), and/or systemic risk factors (i.e. autoimmune or skin disorders) for developing post-operative infection. If the swab was found positive, an antimicrobial susceptibility test was performed, and a specific antibiotic therapy was administered. Surgery was performed when a repeat conjunctival swab (after antibiotic treatment) showed negative cultures. RESULTS: Cultures were found positive in 25.3% of patients. Staphylococcus aureus (18%) and Staphylococcus epidermidis (15%) were the most frequently isolated microorganisms. Gram-negative bacteria, including Pseudomonas aeruginosa, were present in nine cases (8%). CONCLUSION: Present results showed a low rate of swab positivity compared to previous published data, and slightly different microbial flora. The differences observed may be caused by geographical factors and/or to the specific characteristics of the subgroup of studied patients. Considering that the surface microbial flora is one of the major causes of endophthalmitis, this information may be useful in selecting antibacterial regimens to prevent serious ocular infections, and restrain the increasing problem of antibiotic resistance.

Worsening of gas exchange parameters at high FiO2 in COVID-19: misleading or informative?

BACKGROUND: In COVID-19, higher than expected level of intrapulmonary shunt has been described, in association with a discrepancy between the initial relatively preserved lung mechanics and the hypoxia severity. This study aim was to measure the shunt fraction and variations of PaO2/FiO2 ratio and oxygen alveolar-arterial gradient (A-a O2) at different FiO2. METHODS: Shunt was measured by a non-invasive system during spontaneous breathing in 12 patients hospitalized at COVID-19 Semi-Intensive Care Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, between October 22 and November 23, 2020. RESULTS: Nine patients were men, mean age (±SD) 62±15 years, mean BMI 27.5±4.8 Kg/m2. Systemic hypertension, diabetes type 2 and previous myocardial infarction were referred in 33%, 17%, and 7%, respectively. Mean PaO2/FiO2 ratio was 234±66 and 11 patients presented a bilateral chest X-ray involvement. Mean shunt was 21±6%. Mainly in patients with a more severe respiratory failure, we found a progressive decrease of PaO2/FiO2 ratio with higher FiO2. Considering (A-a O2), we found a uniform tendency to increase with FiO2 increasing. Even in this case, the more severe were the patients, the higher was the slope, suggesting FiO2 insensitiveness due to a shunt effect, as strengthened by our measurements. CONCLUSION: Relying on a single evaluation of PaO2/FiO2 ratio, especially at high FiO2, could be misleading in COVID-19. We propose a two steps evaluation, the first at low SpO2 value (e.g., 92-94%) and the second one at high FiO2 (i.e., >0.7), allowing to characterize both the amendable (ventilation/perfusion mismatch), and the fixed (shunt) contribution quote of respiratory impairment, respectively.

Confocal Microscopy and Anterior Segment Optical Coherence Tomography Imaging of the Ocular Surface and Bleb Morphology in Medically and Surgically Treated Glaucoma Patients: A Review.

Glaucoma patients often suffer from ocular surface disease (OSD) caused by the chronic administration of topical anti-glaucoma medications, especially in cases of long-term therapy with preserved or multiple drugs. Additionally, glaucoma surgery may determine ocular surface changes related to the formation and location of the filtering bleb, the application of anti-mitotic agents, and the post-operative wound-healing processes within the conjunctiva. Recently, several studies have evaluated the role of advanced diagnostic imaging technologies such as in vivo confocal microscopy (IVCM) and anterior segment-optical coherence tomography (AS-OCT) in detecting microscopic and macroscopic features of glaucoma therapy-related OSD. Their clinical applications are still being explored, with recent particular attention paid to analyzing the effects of new drug formulations and of minimally invasive surgical procedures on the ocular surface status. In this review, we summarize the current knowledge about the main changes of the ocular surface identified at IVCM and AS-OCT in glaucoma patients under medical therapy, or after surgical treatment.

Glaucoma and neuroinflammation: An overview.

Glaucoma is an optic neuropathy characterized by well-defined optic disc morphological changes (i.e., cup enlargement, neuroretinal border thinning, and notching, papillary vessel modifications) consequent to retinal ganglion cell loss, axonal degeneration, and lamina cribrosa remodeling. These modifications tend to be progressive and are the main cause of functional damage in glaucoma. Despite the latest findings about the pathophysiology of the disease, the exact trigger mechanisms and the mechanism of degeneration of retinal ganglion cells and their axons have not been completely elucidated. Neuroinflammation may play a role in both the development and the progression of the disease as a result of its effects on retinal environment and retinal ganglion cells. We summarize the latest findings about neuroinflammation in glaucoma and examine the connection between risk factors, neuroinflammation, and retinal ganglion cell degeneration.

Single-Pass Mikrokeratome and Anterior Chamber Pressurizer for the Ultrathin Descemet-Stripping Automated Endothelial Keratoplasty Graft Preparation.

PURPOSE: To compare the reliability of microkeratome dissection with the anterior chamber pressurizer (ACP) system versus conventional pressurization for ultrathin Descemet-stripping automated endothelial keratoplasty (UT-DSAEK) graft preparation. METHODS: A retrospective review of a consecutive series of dissected donor corneas processed at Pavia Eye Bank for UT-DSAEK surgery was performed. Grafts were prepared through single-pass microkeratome dissection with artificial anterior chamber internal pressure regulation through either ACP or the conventional method using a water column with tube clamp. The target central graft thickness (CGT) was ≤100 µm. Cutting predictability was determined as the difference between the microkeratome head size and the thickness actually removed. Graft regularity was investigated as central-to-peripheral thickness increase, central-to-peripheral (CP) ratio, and graft thickness uniformity. Thickness was measured with anterior segment optical coherence tomography (horizontal and vertical meridians). RESULTS: Of the 265 UT-DSAEK grafts, ACP achieved the target "CGT ≤ 100 µm" in 87 of 120 (72.5%), whereas the conventional technique achieved the same in 85 of 145 (58.6%) (P = 0.018). ACP predictability was -3.9 µm (SD: 2.3), whereas predictability of the conventional technique was -54.6 µm (SD: 3.7) (P < 0.001). Thickness increased similarly (P = 0.212); CP ratio was better with ACP for only 2 mm diameter (P = 0.001); graft thickness uniformity was comparable (P > 0.05). CONCLUSIONS: Compared with conventional pressurization, ACP improved microkeratome-assisted preparation reliability of UT-DSAEK grafts, achieving CGT ≤ 100 µm with significantly higher frequency (P = 0.018) and predictability (P < 0.001). ACP improved CP ratio only at 2 mm (P = 0.001); for other graft thickness, the 2 methods proved equivalent.