Association of Broad-Spectrum Antibiotic Therapy and Vitamin E Supplementation with Vitamin K Deficiency-Induced Coagulopathy: A Case Report and Narrative Review of the Literature.

Vitamin K is a lipid-soluble vitamin that is normally maintained within appropriate levels by means of dietary intake and bacterial production in the intestinal microflora. It holds a central role in coagulation homeostasis, and thus its depletion leads to hypocoagulation and haemorrhagic diathesis. The association of antibiotic therapy and vitamin E supplementation with vitamin K deficiency was previously described in animal experiments, clinical studies, and case reports. Broad-spectrum antibiotic therapy potentially leads to intestinal microflora dysbiosis and restriction of vitamin K-producing bacterial populations, resulting in decreased vitamin K levels, whereas antibiotics of the cephalosporin class with 1-N-methyl-5-thiotetrazole (NMTT) or 2-methyl-1,3,4-thiadiazole (MTD) side groups inhibit vitamin K function. Vitamin E supplementation interferes with both the bioavailability and function of vitamin K, yet its mechanisms are not fully understood. We present the case of a 45-year-old male patient, with a history of epilepsy and schizophrenia, catatonically incapacitated and immobilised, who was hospitalised in our centre for the investigation and management of aspiration pneumonia. He demonstrated a progressively worsening prolongation of international normalised ratio (INR), which was attributed to both broad-spectrum antibiotic therapy and vitamin E supplementation and was reversed upon administration of vitamin K. We highlight the need for close monitoring of coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, and we further recommend the avoidance of NMTT- or MTD-containing antibiotics or vitamin E supplementation, unless absolutely necessary, in those patients.

Three-Year Results of Simultaneous Transepithelial Phototherapeutic Keratectomy and Conventional Photorefractive Keratectomy (Cretan Protocol Plus) Followed by Corneal Crosslinking for Keratoconus.

PURPOSE: The aim of this study was to present the 3-year outcomes after simultaneous transepithelial phototherapeutic keratectomy (t-PTK) and conventional photorefractive keratectomy (PRK) followed by corneal crosslinking (CXL) for keratoconus. METHODS: In this prospective, interventional case series, patients with progressive keratoconus underwent simultaneous t-PTK and conventional PRK followed by CXL (Cretan protocol plus). Visual, refractive, and topographic outcomes were evaluated along with endothelial cell density (ECD) preoperatively and at 1, 2, and 3 years postoperatively. RESULTS: Twenty-two patients (31 eyes) were enrolled. No intraoperative or postoperative complications were observed in any of the patients. Logarithm of the minimum angle of resolution (logMAR) mean uncorrected and mean corrected distance visual acuity improved from 0.81 ± 0.40 and 0.18 ± 0.21 preoperatively to 0.38 ± 0.33 ( P < 0.001) and 0.06 ± 0.12 ( P < 0.001) at 3-year follow-up. Mean spherical equivalent improved from -5.39 ± 3.89 diopters (D) preoperatively to -2.29 ± 2.65 D ( P < 0.001) at 3 years postoperatively. Mean corneal astigmatism reduced from -4.70 ± 2.86 D preoperatively to -3.55 ± 2.45 D ( P = 0.001) at 3 years postoperatively. No ECD alterations were observed throughout the 3-year follow-up ( P > 0.05). CONCLUSIONS: Simultaneous t-PTK and conventional PRK followed by CXL seems to be an effective and safe treatment for progressive keratoconus over 3-year follow-up.

A systematic review and meta-analysis of early and late outcomes after endovascular angioplasty among patients with thromboangiitis obliterans and chronic limb ischemia.

BACKGROUND: No consensus has yet been reached regarding the optimal treatment of patients with thromboangiitis obliterans (TO) and chronic limb ischemia. In the present study, we aimed to summarize the results on endovascular treatment of such patients. METHODS: We performed a meta-analysis using the following databases: PubMed, Scopus, and the Cochrane Library. The eligible studies had been reported up to December 2021 and had evaluated endovascular angioplasty to treat patients with TO and chronic limb ischemia. The early (mortality and technical success) and late (primary/secondary patency and limb salvage) outcomes were evaluated. StatsDirect (StatsDirect Ltd, Merseyside, UK) was used for the statistical analysis. RESULTS: Overall, 15 eligible studies were included (only endovascular in 11 studies and both endovascular and open repair in 4 studies). Among 601 patients, 402 endovascular procedures (416 limbs) were recorded (angioplasty plus stenting for 7.2% and angioplasty plus thrombolysis for 3.7%). The clinical presentation was intermittent claudication (stage II-III) for 7.9% of the patients and critical ischemia (stage IV-VI) for 92.1% of the patients. Most of the patients had had lesions below the knee, and five had had upper extremity lesions. The pooled technical success rate was 86% (range, 81.1%-90.3%), with no in-hospital mortality. The other complications included perforations (1.9%), wound complications (2.2%), and distal embolism (0.2%). Primary patency was 65.7% (range, 52.7%-77.6%) at 12 months and 50.7% (range, 23.3%-77.9%) at 36 months. Secondary patency was 76.2% (range, 57.5%-90.8%) at 12 months and 64.5% (range, 32.3%-90.6%) at 36 months. The limb salvage rate was 94.1% (range, 90.7%-96.7%) at 12 months and 89.1% (range, 80.6%-95.4%) at 36 months. CONCLUSIONS: Endovascular angioplasty for patients with TO and chronic limb ischemia was associated with optimal safety and low complication rates. The technical success and late outcomes were acceptable.

Individualized dosimetry in Ru-106 ophthalmic brachytherapy based on MRI-derived ocular anatomical parameters.

PURPOSE: To estimate ocular geometry-related inaccuracies of the dosimetric plan in Ru-106 ophthalmic brachytherapy. METHODS AND MATERIALS: Thirty patients with intraocular lesions were treated with brachytherapy using a Ru-106 plaque-shell of inner radius of 12 mm. Magnetic resonance imaging was employed to determine the external scleral radius at tumor site and the tumor margins. A mathematical model was developed to determine the distance between the external sclera and the internal surface of the plaque associated with the tangential application of the plaque on the treated eye. Differences in delivered dose to the tumor apex, sclera and tumor margins as derived by considering the default eye-globe of standard size (external sclera radius = 12 mm) against the individual-specific eye globe were determined. RESULTS: The radius of external sclera at the tumor site was found to range between 10.90 and 13.05 mm for the patient cohort studied. When the patient specific eye-globe/tumor geometry is not taken into account, the delivered dose was found to be overestimated by 8.1% ± 4.1% (max = 15.3%) at tumor apex, by 1.5% ± 2.8% (max = 5.7%) at anterior tumor margin, by 16.6% ± 7.5% (max = 36.4%) at posterior tumor margin and 8.1% ± 3.8% (max = 13.2%) at central sclera of eyes with lower than the default radius. The corresponding dose overestimations for eyes with higher than the default radius was 13.5% ± 4.3% (max = 22.3%), 1.5% ± 2.8% (max = 5.7%), 12.6% ± 4.5% (max = 20.0%), and 15.1% ± 5.0% (max = 24.4%). CONCLUSIONS: The proposed patient-specific approach for Ru-106 brachytherapy treatment planning may improve dosimetric accuracy. Individualized treatment planning dosimetry may prevent undertreatment of intraocular tumors especially for highly myopic or hyperopic eyes.

New paradigms in minimally-invasive vascular surgery.

INTRODUCTION: Vascular surgery has been greatly evolved during the last decades and novel minimally invasive techniques have been introduced. Aim of this review is to briefly present all these advances and compare them with traditional repairs. AREAS COVERED: The authors have extensively searched literature through the Pubmed and Embase databases. All articles published up to December 2021 referring to minimally invasive techniques used for treatment of peripheral artery disease, carotid disease, aortic aneurysms, and venous disease were evaluated. Minimally invasive techniques under investigation included endovascular and hybrid techniques, robot-assisted and laparoscopic approaches. EXPERT OPINION: Several minimally invasive techniques such as endovascular and hybrid approaches have been extensively used during the last two decades to treat vascular surgery patients offering them lower mortality and morbidity risks. Novel robot-assisted techniques have shown promising results in preclinical studies although further clinical evaluation is needed.

Late-onset inverse Bell's phenomenon after upper eyelid trauma.

Bell's phenomenon evaluation is an important part of preoperative patient assessment for eyelid surgeries. Inverse Bell's phenomenon is a rare manifestation, usually observed in the early postoperative period following ptosis restoration surgeries, in pathological conditions, and in a small proportion of normal population. In the current case report, a 6-year-old girl presented with late-onset posttraumatic inverse Bell's phenomenon, 6 months after facial trauma with posttraumatic lagophthalmos. Rehabilitative blepharoplasty for the correction of lagophthalmos led to the restoration of inverse Bell's phenomenon 3 months postoperatively. Potential causative mechanisms are discussed for this late-onset manifestation of inverse Bell's response.

Association between HPV detection in swab samples and tissue specimens and ophthalmic pterygium recurrence.

PURPOSE: To investigate the presence of HPV on the ocular surface after surgical excision of HPV infected pterygia and the possible correlation of HPV with pterygium postoperative recurrence. MATERIALS AND METHODS: Both exfoliative pterygium swab samples and respective tissue specimens were received and analyzed with real-time PCR for the detection of HPV-infected pterygia. In addition, swab samples from patients that had HPV-infected pterygia with no recurrence after 1 year of follow-up, as well as swab samples from patients with healthy conjunctiva, were analyzed. RESULTS: Forty eyes with pterygium of 40 patients and 40 eyes with normal conjunctiva were included in the study. HPV virus was detected in the tissue specimens of 11 patients (27.5%) and in the swabs of 9 patients (22.5%). The HPV subtypes detected were 33, 39, 45, 56, 59, 66, and 68. The swab test had sensitivity of 81.82% and 100% specificity. In 15 (43%) patients, a bare sclera technique was used for pterygium removal and eleven of these patients showed recurrence of the disease. Surgical excision with use of autologous conjunctival graft was performed in twenty patients and five of them had recurrence. Patients with recurrent disease were 12.41 times more likely to have an HPV-infected pterygium (p = 0.031). Furthermore, from the 11 HPV positive patients, six had no recurrence, 1 year after surgery. In five of them, a swab sample was taken from the site of the surgical excision 1 year after surgery and real-time PCR was negative for HPV presence. CONCLUSION: Persistence of HPV infection seems to be correlated with postoperative pterygium recurrence. Further investigation with the use of the minimally invasive proposed swab technique may contribute in the understanding of pterygium pathogenesis and in the development of a more efficient treatment planning.

MRI and dual-energy CT fusion anatomic imaging in Ru-106 ophthalmic brachytherapy.

PURPOSE: Brachytherapy with Ru-106 is widely used for the treatment of intraocular tumors, and its efficacy depends on the accuracy of radioactive plaque placement. Ru-106 plaques are MRI incompatible and create severe metal artifacts on conventional CT scans. Dual-energy CT scans (DECT) may be used to suppress such artifacts. This study examines the possibility of creating fusion images from MRI scans (preoperatively) and DECT scans (with the plaque in place) as a tool for confirming the anatomic accuracy of plaque placement. METHODS AND MATERIALS: Six patients with intraocular lesions (5 with choroidal melanoma and 1 with a retinal vasoproliferative lesion) were included. Fusion images of preoperative MRI scans and DECT scans with the plaque in place were created with the Demo version of the ImFusion suite (ImFusion GmbH, Munchen Germany). Clearance margins between the tumor and plaque edge in axial, transverse, and coronal planes as well as the elevation of the posterior plaque edge from the sclera were recorded and associated with the location of the lesion. RESULTS: Plaque-tumor clearance margins for transverse, sagittal, and coronal planes were higher for anteriorly located lesions (5.13 mm ± 0.11 [5.0-5.2], 5.10 mm ± 0.26 [4.9-5.4], and 5.33 mm ± 0.45 [4.9-5.8] respectively) than for posteriorly located lesions (4.16 mm ± 1.44 [2.5-5.1], 4.13 mm ± 1.42 [2.5-5.1], and 4.2 mm ± 1.21 [2.8-5.0], respectively). The elevation of the posterior plaque edge from the sclera was 0.33 mm ± 0.28 [0-0.5] and 0.63 mm ± 0.60 [0.7-1.2] for posterior and anterior lesions, respectively. CONCLUSIONS: Fusion images between DECT and MRI scans may be used as a tool to confirm the accuracy of Ru-106 plaque placement in relation with the intraocular tumors in ophthalmic brachytherapy.

Dual-energy CT imaging of orbits during episcleral brachytherapy with Ru-106 plaques: A phantom study on its potential for plaque position verification.

PURPOSE: To investigate the potential of dual energy CT (DECT) to suppress metal artifacts and accurately depict episcleral brachytherapy Ru-106 plaques after surgical placement. METHODS: An anthropomorphic phantom simulating the adult head after surgical placement of a Ru-106 plaque was employed. Nine DECT acquisition protocols for orbital imaging were applied. Monochromatic 140 keV images were generated using iterative reconstruction and an available metal artifact reduction algorithm. Generated image datasets were graded by four observers regarding the ability to accurate demarcate the Ru-106 plaque. Objective image quality and visual grading analysis (VGA) was performed to compare different acquisition protocols. The DECT imaging protocol which allowed accurate plaque demarcation at minimum exposure was identified. The eye-lens dose from orbital DECT, with and without the use of radioprotective bismuth eye-shields, was determined using Monte Carlo methods. RESULTS: All DECT acquisition protocols were judged to allow clear demarcation of the plaque borders despite some moderate streaking/shading artifacts. The differences between mean observers' VGA scores for the 9 DECT imaging protocols were not statistically significant (p > 0.05). The eye-lens dose from the proposed low-exposure DECT protocol was found to be 20.1 and 22.8 mGy for the treated and the healthy eye, respectively. Bismuth shielding was found to accomplish >40% reduction in eye-lens dose without inducing shielding-related artifacts that obscure plaque delineation. CONCLUSIONS: DECT imaging of orbits after Ru-106 plaque positioning for ocular brachytherapy was found to allow artifact-free delineation of plaque margins at relatively low patient exposure, providing the potential for post-surgery plaque position verification.

Long-term Comparison of Combined t-PTK and CXL (Cretan Protocol) Versus CXL With Mechanical Epithelial Debridement for Keratoconus.

PURPOSE: To compare the long-term outcomes of corneal cross-linking (CXL) for the treatment of keratoconus using two different techniques for epithelial removal: transepithelial phototherapeutic keratectomy (t-PTK) and mechanical epithelial debridement. METHODS: In this prospective, comparative, interventional case series, 26 patients (30 eyes) with progressive keratoconus underwent CXL treatment. Fifteen eyes (13 patients) underwent epithelial removal with t-PTK (Cretan protocol) and 15 eyes (13 patients) underwent mechanical epithelial debridement (Dresden protocol) during CXL. Visual, refractive, and keratometric outcomes were evaluated preoperatively and at 1, 2, 3, and 4 years postoperatively. RESULTS: No intraoperative or postoperative complications were observed in any of the patients. In the Cretan protocol group, mean uncorrected (UDVA) and corrected (CDVA) visual acuity improved from 0.99 ± 0.42 and 0.33 ± 0.28 logMAR preoperatively to 0.75 ± 0.32 (P = .018) and 0.21 ± 0.16 (P = .024) logMAR at 4 years postoperatively, respectively. In the Dresden protocol group, mean UDVA improved from 0.83 ± 0.47 logMAR preoperatively to 0.63 ± 0.40 logMAR (P = .033) at 4 years postoperatively, whereas mean CDVA did not demonstrate a statistically significant improvement postoperatively (P > .05). In the Cretan protocol group, mean corneal astigmatism improved from -6.19 ± 4.54 diopters (D) preoperatively to -4.68 ± 3.10 D (P = .041) at last follow-up, whereas in the Dresden protocol group there was no statistically significant difference postoperatively (P > .05). CONCLUSIONS: Epithelial removal with t-PTK during CXL (Cretan protocol) resulted in better visual, refractive, and keratometric outcomes compared with mechanical epithelial debridement over a long-term follow-up. [J Refract Surg. 2019;35(10):650-655.].

Systematic review and meta-analysis of randomized controlled trials evaluating long-term outcomes of endovenous management of lower extremity varicose veins.

BACKGROUND: Early studies have demonstrated that endovenous therapy for varicose veins is associated with a faster recovery and lower complication rates compared with conventional therapy. More than one million procedures have been performed worldwide. The objective of this study was to determine long-term efficacy of currently available endovenous therapy methods for varicose veins compared with conventional surgery (saphenofemoral ligation and stripping of great saphenous vein [GSV] with or without multiple avulsions) in management of GSV-related varicose veins. METHODS: In July 2017, we searched MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Scopus, Cochrane Library, and Web of Science without date or language restriction for relevant randomized controlled trials (RCTs). Bibliographies of included studies were also searched for additional studies. RCTs comparing conventional surgery and endovenous therapy for treating lower extremity varicose veins with 5 years or more of follow-up were selected. Data extraction and quality assessment were performed independently by two review authors, and any disagreements were resolved by consensus or by arbitration of a third author. Cochrane RevMan 5 was used for analysis. RESULTS: At time of data extraction, long-term follow-up was available for endovenous laser therapy (EVLT), radiofrequency ablation (RFA), and ultrasound-guided foam sclerotherapy. Included in the review were nine RCTs. The RCTs included 2185 legs; however, only 1352 legs were followed up for 5 years (61.9%). There was no statically significant difference in recurrence rate in comparing EVLT with conventional surgery in treating GSV incompetence (36.6% vs 33.3%, respectively; pooled risk ratio, 1.35; 95% confidence interval, 0.76-2.37; P = .3). Also, no significant difference was determined for recurrence rate in comparing RFA with surgery or EVLT. CONCLUSIONS: Although the analysis showed that EVLT and RFA are as effective as conventional surgery in treating saphenous venous insufficiency, the number of patients available for analysis was too small for definitive conclusions to be drawn.

Mini descemet membrane stripping (m-DMES) in patients with Fuchs' endothelial dystrophy: A new method.

We present two cases with focal corneal edema due to Fuchs' endothelial dystrophy that were successfully treated with mini Descemet membrane stripping (m-DMES) (diameter of 3-4 mm; at the area of preexisting focal corneal edema) without endothelial replacement during cataract surgery. Specular microscopy demonstrated Fuchs' endothelial dystrophy and histopathologic evaluation confirmed the diagnosis. Anterior segment optical coherence tomography and confocal microscopy were used for the evaluation of the corneal tissue recovery course after the surgical procedure. In both patients, we observed an initial aggravation of corneal edema in the area of DM removal for two months followed by gradual improvement. At four months postoperatively, corneal edema had completely regressed resulting in corneal clearance and visual acuity improvement in both cases. M-DMES without graft insertion represents a promising alternative surgical technique that could be applied in specific cases of Fuchs' endothelial dystrophy with focal corneal edema.

The beneficial role of simultaneous splenectomy after extended hepatectomy: experimental study in pigs.

BACKGROUND: The role of hepatic hemodynamic modulation in the development of "small-for-size" syndrome (SFSS) after extended hepatectomy (EH) or living-donor liver transplantation is still controversial. We have designed an experimental study to investigate the effect of hemodynamic parameters of the liver circulation on the development of SFSS after EH in a porcine model. METHODS: Eighteen pigs were randomly divided into two groups: group A has received EH (75%-80%) without splenectomy, and group B with EH and simultaneous splenectomy was carried out. Portal hemodynamics, liver function tests, histologic findings, injury and survival rates were compared between groups A and B. RESULTS: The 7-d survival rate in the splenectomy group was significantly improved compared with group A (88.9% versus 44.4%, P < 0.05). Portal vein pressure, portal vein flow, and liver function tests in the splenectomy group were significantly lower than in group A immediately after splenectomy and postoperatively until the day of sacrifice. Histologic findings in group A clearly illustrate severe inflammation, bridging necrosis, ischemic cholangitis, and severe congestion, while in group B there were less serious histologic changes. CONCLUSIONS: Our experimental study indicates that perioperative portal modulation can successfully prevent the manifestation of SFSS after EH. Therefore, by focusing on "flow" rather than on "size," researchers may understand better the pathophysiology of this syndrome.

Corneal Stromal Demarcation Line Depth Following Standard and a Modified High Intensity Corneal Cross-linking Protocol.

PURPOSE: To compare the corneal stromal demarcation line depth using anterior segment optical coherence tomography (AS-OCT) after corneal cross-linking (CXL) using two different treatment protocols: the standard Dresden protocol (30 minutes with 3 mW/cm(2)) and a modified high intensity protocol (7 minutes with 18 mW/cm(2)), corresponding to a total surface dose of 5.4 and 7.5 J/cm(2), respectively. METHODS: This prospective, comparative, interventional case series included 29 keratoconic patients (32 eyes). All patients underwent CXL using the same high intensity ultraviolet-A (UV-A) irradiation device (CCL-365; Peschke Meditrade GmbH, Huenenberg, Switzerland). Sixteen eyes were treated for 30 minutes with 3 mW/cm(2) according to the standard Dresden protocol, whereas 16 eyes were treated with a novel modified high intensity CXL protocol for 7 minutes with 18 mW/cm(2) of UV-A irradiation intensity. One month postoperatively, corneal stromal demarcation line depth was measured by two independent observers using AS-OCT. RESULTS: There was no significant difference in corneal stromal demarcation line depth between observer measurements for both groups (P = .645, Dresden protocol group; P = .715, high intensity group). Mean corneal stromal demarcation line depth was 341.81 ± 47.02 µm for the Dresden protocol group and 313.37 ± 48.85 µm for the high intensity protocol group. There was no statistically significant difference (P = .104) in the corneal stromal demarcation line depth between the two groups. Mean endothelial cell density did not change significantly in either group (P = .090, Dresden protocol group; P = .103, high intensity group). No intraoperative or postoperative complications were noted. CONCLUSIONS: Corneal stromal demarcation line depth using UV-A irradiance with 3 mW/cm(2) for 30 minutes and 18 mW/cm(2) for 7 minutes was similar. It seems that the current modified accelerated CXL protocol provided the same treatment depth as the standard Dresden protocol.

Multiorganism, drug-resistant keratitis treated by corneal crosslinking.

PURPOSE: To describe a case of multiorganism, drug-resistant keratitis that responded well to corneal crosslinking (CXL) treatment. METHODS: A 52-year-old man presented to our institute with a 2-month ocular history of infectious keratitis in his right eye, on topical antibacterial, antifungal, and antiprotozoan treatment, and complained of increase in pain, discomfort, and visual deterioration. Slit-lamp examination revealed advanced infectious keratitis (extensive deep corneal infiltrate with perineuritis). Cultural and molecular analysis of obtained corneal specimens demonstrated combined fungal and Acanthamoeba infection; confocal microscopy confirmed Acanthamoeba infection. Intense targeted topical antifungal and antiprotozoan treatment was initiated immediately and 1 month later CXL was performed due to drug resistance of the infection. RESULTS: Two weeks after CXL treatment, the corneal findings had deteriorated, while a corneal abscess was formed and extended at almost half of the cornea. This was gradually limited and the corneal infiltrate and abscess were eventually decreased. In addition, the symptoms improved. CONCLUSIONS: Corneal crosslinking could be an effective therapy in the management of advanced infectious keratitis unresponsive to conventional medical treatment.

Pupil response to tropicamide following corneal crosslinking.

PURPOSE: To evaluate the effect of corneal crosslinking (CXL) with ultraviolet A (UVA) irradiation on pupil response to tropicamide 0.5% instillation. METHODS: This prospective interventional study enrolled 17 patients (19 eyes) with progressive keratoconus who underwent CXL with UVA irradiation. Central corneal thickness (CCT) was evaluated with the use of anterior segment optical coherence tomography (Visante OCT 3.0). Pupil diameter was measured with the use of Colvard infrared pupillometer before the instillation of tropicamide 0.5% and after the instillation of tropicamide every 5 minutes for total duration of 30 minutes. Corneal epithelial integrity was examined with the use of fluorescein dye staining. Measurements were performed 1 day preoperatively and 1 month postoperatively, with emphasis on simulating the same light conditions regarding the pupil measurements. RESULTS: No intraoperative or postoperative complications were observed in any of the patients. Mean CCT decreased significantly (p<0.001) 1 month postoperatively. Mean postoperative pupil size did not change significantly at any time point compared to the mean preoperative measurements. CONCLUSIONS: The CXL procedure seems not to impair effectiveness of topical drugs, using pupil size measurements after tropicamide 0.5% instillation.