Suitability and Early Clinical Outcomes of Corneal Donor Tissue in the 76-80-Year-Old Age Group.

PURPOSE: There is a significant global shortage of corneal donor tissue suitable for keratoplasty. One simple strategy for addressing this shortage is to increase the upper age limit for acceptable tissue over the current customary upper limit of age 75. We describe a pilot study completed at one eye bank procuring, processing, and distributing keratoplasty tissue from donors aged 76 to 80 years. METHODS: This is a retrospective case series of donor tissues aged 76 to 80 years in comparison with donor tissues aged 71 to 75 years. Standard tissue parameters were evaluated for all tissues, including tissue suitability, mean endothelial cell density (ECD), death-to-procurement time, and cause of death. For the older tissues, clinical outcomes through 3 months were obtained from each surgeon, including intraoperative and postoperative complications. RESULTS: Corneal tissues from donors aged 76 to 80 years had a similar suitability rate (57%) when compared with donors aged 71 to 75 years (59%) (P = 0.635). Both groups had comparable ECDs (P = 0.097). Early clinical outcomes of corneal grafts from donors older than 76 years were favorable, with no early graft failure or significant concerns for clinical safety or efficacy. CONCLUSIONS: Our findings suggest that corneal tissues aged 76 to 80 years can be safely and efficiently transplanted in the United States. While additional study is needed, our results strengthen the case that expanding the upper age limit for donor age has the potential to help meet the global shortage for suitable keratoplasty tissue.

Dexamethasone Intracanalicular Insert versus Standard Topical Steroids for the Prophylaxis of Inflammation after Cataract Surgery.

PURPOSE: To compare the efficacy of an intracanalicular dexamethasone intracanalicular insert (DII) to a topical prednisolone acetate 1% taper for preventing breakthrough inflammation (iritis or cystoid macular edema [CME]) during the first postoperative month (POM1) after cataract surgery. DESIGN: Retrospective, nonrandomized comparative interventional study. METHODS: Patients received either DII or topical prednisolone acetate 1% eyedrops (control) during POM1. Exclusion criteria included history of iritis, glaucoma, intraoperative posterior capsular rupture or vitreous prolapse, immediate postoperative anterior chamber inflammation requiring treatment, or less than 1 month follow-up postoperatively. Outcomes included development of breakthrough inflammation after >3 days postoperatively necessitating additional antiinflammatory drops, CME, and increased intraocular pressure (IOP) at POM1. RESULTS: A total of 266 eyes of 174 patients were included in the DII group and 258 eyes of 167 patients in the control group. Demographics, comorbidities, and baseline IOP were comparable between groups. The breakthrough inflammation rate was significantly higher in the DII group compared to control (9.0% vs 3.1%; P < .01); CME rates were similar between groups (4.9% vs 4.3%; P = .75). There were no cases of increased IOP >10 mm Hg at POM1 compared to baseline in either group. CONCLUSIONS: After cataract surgery, DII demonstrated a higher rate of breakthrough inflammation than a standard topical steroid regimen with no significant differences in CME rate or IOP increase; however, overall, the rate of postoperative complications was low. DII can be a safe and effective alternative to topical corticosteroid therapy after cataract surgery.

Ion mobility-tandem mass spectrometry of bulky tert-butyl thiol ligated gold nanoparticles.

Gold nanoparticles (AuNPs) synthesized in the 1-3 nm range have a specific number of gold core atoms and outer protecting ligands. They have become one of the "hot topics" in recent decades because of their interesting physical and chemical properties. The characterization of their structures is usually achieved by crystal X-ray diffraction although the structures of some AuNPs remain unknown because they have not been successfully crystallized. An alternative method for studying the structure of AuNPs is electrospray ionization-ion mobility-tandem mass spectrometry (ESI-IM-MSMS). This research evaluated how effectively ESI-IM-MSMS using the commercially available Waters Synapt XS instrument yielded useful structural information from two AuNPs; Au23 (S-tBu)16 and Au30 (S-tBu)18 . The study used the maximum range of available collision energies along with ion mobility separation to measure the energy-dependence of the product ions and their drift times which is a measure of their spatial size. For Au23 (S-tBu)16 , the dissociation gave the masses of the outer protecting monomeric [RS-Au-SR] and trimeric [SR-Au-SR-Au-SR-Au-SR] staples where R = tBu, and complete dissociation of the outer layer Au and tBu groups to reveal the Au15 S8 core. For Au30 (S-tBu)18 , the dissociation products was primarily through the loss of the partial ligands S-tBu and tBu from the outer protecting layer and the loss of single Au4 (S-tBu)4 unit. These results showed the that ESI-IM-MSMS analysis of the smaller Au23 (S-tBu)16 gave information on all it major structural components whereas for Au30 (S-tBu)18 , the overall structural information was limited to the ligands of the outer layer.

Retrospective Analysis of the Real-World Utilization of 4-Factor Prothrombin Complex Concentrate and Plasma in Oral Anticoagulant-Associated Bleeding in US Hospitals.

Real-world utilization of 4-factor prothrombin complex concentrate (4F-PCC) and plasma for the management of oral anticoagulant (OAC)-associated bleeding in US trauma hospitals was described.This is amulticenter, retrospective chart review evaluating the use of 4F-PCC and plasma in OAC reversal across medical specialties. Physicians completed a survey and extracted data from 3 to 5 patient charts. Variables of interest included medical specialty, urgency, and bleed type. Two hundred and thirty-five physicians completed the survey, and 861 patient charts were included in the study. 4F-PCC was commonly used in life-threatening or emergent indications, whereas plasma was used in emergent and urgent indications. Plasma was used mostly for patients on warfarin (53% vs 47% 4F-PCC) and 4F-PCC for those on apixaban (82% vs 18% plasma) and rivaroxaban (77% vs 23% plasma). This retrospective analysis showed that 4F-PCC was predominantly used for OAC reversal despite available specific reversal agents for some of the OAC. Although it is not recommended by any reversal guidelines, plasma is still used for OAC reversal. Plasma should be avoided in the management of OAC-associated bleeding.

Clinical outcomes of prestripped, prestained, and preloaded Descemet's membrane endothelial keratoplasty ("P3 DMEK").

PURPOSE: Despite faster healing and reduced risk of rejection, some surgeons are hesitant to adopt Descemet membrane endothelial keratoplasty (DMEK) due to difficult intraoperative tissue preparation. Use of eye bank prestripped, prestained, and preloaded (p3) DMEK tissue can reduce the learning curve and risk of complications. MATERIALS AND METHODS: We conducted a prospective study including 167 eyes undergoing p3 DMEK and compared outcomes to a retrospective chart review of 201 eyes that underwent standard DMEK surgery. The primary outcomes were graft failure, detachment, and re-bubbling frequency. The secondary outcomes included baseline and postoperative visual acuity at months 1, 3, 6, and 12. Baseline and postoperative central corneal thickness (CCT) and endothelial cell counts (ECC) were collected. RESULTS: ECC decrease for p3 DMEK at 3, 6, and 12 months were 15.0%, 18.0%, and 21.0%, respectively. Forty (24%) of p3 DMEK and 72 (35.8%) of standard DMEK eyes had at least a partial graft detachment. There was no difference in CCT, graft failures, or re-bubble frequency. At 6 months, mean visual acuity was 20/26 and 20/24 for standard and p3 DMEK, respectively. Mean case time for p3 DMEK with phaco or p3 DMEK alone was 33 and 24 min, respectively. Mean case time for eyes undergoing DMEK with phaco or DMEK alone was 59 and 45 min, respectively. CONCLUSION: P3 DMEK tissue is safe and can provide excellent clinical outcomes that are comparable to standard DMEK tissue. Eyes undergoing p3 DMEK may have lower graft detachment and ECC loss.

INR and vitamin K-dependent factor levels after vitamin K antagonist reversal with 4F-PCC or plasma.

Restoration of the international normalized ratio (INR) to values <1.5 is commonly targeted to achieve hemostasis in patients with major bleeding or undergoing urgent surgery who are treated using vitamin K antagonists (VKAs). However, the relationship between corrected INR and vitamin K-dependent factor (VKDF) levels for hemostasis is uncertain. We aim to examine the impact of 4-factor prothrombin complex concentrate (4F-PCC) or plasma on INR correction and VKDF restoration and evaluate the relationship between INR values and VKDF levels in patients with acute major bleeding or patients requiring an urgent surgical procedure. Adult patients treated with VKA with an elevated INR (≥2.0 within 3 hours before study treatment) who received 4F-PCC or plasma after major bleeding or before an urgent surgery or invasive procedure were included in this retrospective analysis of data from 2 prospective phase 3b randomized controlled trials. Of the 370 patients included in this analysis, 185 received 4F-PCC, and 185 received plasma. In the 4F-PCC group, 159 of 185 (85.9%) had an INR ≤1.5 at 30 minutes after the end of infusion compared with only 72 of 184 (39.1%) in the plasma group. After 4F-PCC treatment, all VKDF levels exceeded 50% activity regardless of the postinfusion INR value. However, after plasma administration, mean activity levels for factors II and X were <50% at all time points assessed within 3 hours after starting the infusion, regardless of the postinfusion INR value. This retrospective analysis demonstrated that treatment with 4F-PCC among patients treated with VKA rapidly restores VKDFs to hemostatic levels irrespective of the postinfusion INR value, whereas treatment with plasma does not.

Acute Calcific Band Keratopathy as an Adverse Effect of Recombinant Human Nerve Growth Factor (Cenegermin): A Multicenter Case Series.

PURPOSE: Cenegermin, (OXERVATE) a recently Food and Drug Administration-approved topical formulation of recombinant human nerve growth factor, has been used for the treatment of neurotrophic keratopathy (NK). Corneal deposits have been previously reported as a potential adverse effect; however, the clinical characteristics, visual significance, and treatment options have not been fully described. The purpose of this article is to better characterize corneal deposits occurring during treatment with cenegermin for neurotrophic keratopathy. METHODS: This was a retrospective, multicenter consecutive case series. RESULTS: We identified 5 patients from 3 institutions who developed a white opacity in varying layers of the cornea, consistent with calcium deposition, during treatment with cenegermin. In all cases, the opacity occurred rapidly over the course of a few weeks after initiation of treatment. Histopathologic examination of the cornea from one corneal patient demonstrated extensive calcification of the stroma extending to 90% depth. Before treatment, all patients had stage 2 or 3 NK (Mackie classification). The deposits were visually significant in all patients and did not resolve after cessation of cenegermin. There were no differences in age, sex, etiology of the NK, corneal transplant status, or concurrent medications between the patients who developed a deposit and 15 other patients with stage 2 or 3 NK who did not. One patient was successfully treated with superficial keratectomy with ethylenediaminetetraacetic acid chelation, one patient underwent penetrating keratoplasty, and one patient received a Boston keratoprosthesis. CONCLUSIONS: We report the rapid onset of a corneal opacity after initiation of treatment with cenegermin in patients with stage 2 or 3 NK, consistent with acute calcific band keratopathy. This visually significant adverse finding has not previously been described. We could not identify any risk factors for development. We recommend close monitoring of patients receiving cenegermin therapy because the opacity may be irreversible and may require keratoplasty for visual rehabilitation.

Comparison of 4F-PCC in obese and nonobese patients with life-threatening bleeding or requiring emergent surgery.

BACKGROUND: Four-factor prothrombin complex concentrate (4F-PCC) dosing is based on INR and actual body weight (ABW), with maximum doses not to exceed the dose used in patients weighing >100 kg (Kcentra PI). There are limited data comparing the efficacy of 4F-PCC between patients with low body weight ≤100 kg (LoWT) and high body weight >100 kg (HiWT). METHODS: We conducted a retrospective cohort study of patients on warfarin who received 4F-PCC for life-threatening major bleeding or requiring emergent surgery between January 2015 to June 2018 at three academic medical centers. These data were combined with a dataset from 2 randomized Phase 3b clinical trials. RESULTS: We included 388 patients who received 4F-PCC, 318 (82%) were LoWT, and 70 (18%) were HiWT. Indication for 4F-PCC for life-threatening bleeding and emergent surgery was 266 (69%) and 122 (31%) patients, respectively. The most common bleeding type was intracranial hemorrhage (41%), followed by gastrointestinal (36%). The median dose was 2283 units (25 units/kg), and 2.1% of patients required a repeat dose. CONCLUSION: In those >100 kg, we found no difference in achieving international normalized ratio (INR) ≤1.3, hemostasis in intracranial hemorrhage, or thrombosis. In-hospital mortality occurred 15% in LoWt versus 6% in HiWT (CI 1.8%-17%, p = 0.034). Achievement of INR ≤ 1.5 was significantly lower in the LoWT group compared to the HiWT group (80% versus 91%, CI -20% to -2.5%, p = 0.03).

Direct Injection of 5-Fluorouracil Improves Outcomes in Cicatrizing Conjunctival Disorders Secondary to Systemic Disease.

PURPOSE: Conjunctival cicatrizing conditions are vision threatening, with poor outcomes despite aggressive systemic therapy. This study tests the utility of serial injections of 5-fluorouracil (5-FU) into the fornices to treat conjunctival scarring in patients with ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis. METHODS: Retrospective cohort study. Fisher exact test and multivariable logistic regression analyses were used to compare clinical outcomes of patients who were administered 5-FU injections versus patients who were not injected. Model fit was examined for multivariable regression. RESULTS: One hundred twelve eyes (56 patients) met the inclusion criteria. Thirty-eight eyes (34%) had Stevens-Johnson syndrome/toxic epidermal necrolysis, and 74 eyes (66%) were diagnosed with ocular cicatricial pemphigoid. Twenty-five eyes received ≥1 injection of 5-FU. Sixteen eyes received 1-4 injections, while 9 received ≥5. Median follow-up until last encounter was 18 months. Analysis of each disease entity alone and in combination revealed that 5-FU injections were associated with improvement in final visual acuity, corneal scarring, trichiasis, need for/number of mucous membrane graft surgeries, and severity of symblephara. CONCLUSIONS: Serial injection of 5-FU in the affected fornices is a promising treatment for severe vision-threatening conjunctival scarring from ocular cicatricial pemphigoid and Stevens-Johnson syndrome/toxic epidermal necrolysis. Given the excellent safety profile of 5-FU around the eye, the solid biologic foundation for using 5-FU in this setting, and the severe risk of vision loss from these disorders, the authors suggest that serial 5-FU injections be adopted as therapy for conjunctival scarring from ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis despite the limitations of this retrospective study.

Juvenile Osteoid Osteoma of the Distal Phalanx of the Second Digit.

Osteoid osteomas account for approximately 3% to 10% of primary bone tumors and are found most commonly in the cortical, diaphyseal regions of long tubular bones. These osteoblastic, benign tumors are usually seen in males, in the second to third decade, most often in the long bones of the lower extremity. The literature describes the limited encounters with osteoid osteomas of the pedal digital phalanx, especially in the pediatric population. Here, a case report details a juvenile patient with an osteoid osteoma tumor of the distal phalanx in the right second digit that was treated with complete distal phalanx excision in toto, eliminating the patient's pain and symptoms quickly after surgery. Further the literature is reviewed for other examples of this pathology in the similar clinical setting.

Recipient Factors Associated With Graft Detachment of a Subsequent Eye in Sequential Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To evaluate the recipient factors associated with graft detachment in the subsequent eye of patients who underwent sequential Descemet membrane endothelial keratoplasty (DMEK). METHODS: A retrospective, consecutive case series with 158 eyes of 79 patients who underwent DMEK surgeries in both eyes between October 2013 and April 2019 for treatment of Fuchs endothelial dystrophy. The main outcome measure was the presence of graft detachment (any amount of detachment) at postoperative 1 week in the subsequent eye. Preoperative, intraoperative, and postoperative factors were evaluated for association with graft detachment. RESULTS: Of 79 patients (158 eyes) with a mean follow-up of 11.7 ± 8.4 months, 18 patients (36 eyes) developed graft detachment in both eyes 1 week postoperatively. The risk of detachment in the subsequent eye was increased when the first eye had any amount of detachment [odds ratio = 2.8; 95% confidence interval (CI) = 1.1-7.3; P = 0.037]. When the first eye had a clinically significant detachment (>30% detached), the risk of detachment occurring in the subsequent eye was greater (odds ratio = 15.7; 95% CI = 1.8-134.5; P = 0.012). This risk of graft detachment in the subsequent eye increased 33% for every 5% increase in the detachment percentage in the first eye (odds ratio = 1.3; 95% CI = 1.1-1.6; P = 0.008). CONCLUSIONS: The presence of graft detachment after DMEK increases the risk of graft detachment in subsequent DMEK in the contralateral eye. Modification in perioperative care and surgical technique in the contralateral eye, such as a larger gas bubble, use of SF6 20%, and combining cataract surgery, may be needed when graft detachment occurs after DMEK in the first eye.

Endophthalmitis in Advanced Microbial Keratitis: Risk Factors and Examination Findings.

PURPOSE: To evaluate clinical and ultrasonographic findings associated with advanced microbial keratitis with concurrent endophthalmitis. METHODS: We performed a retrospective analytical study of patients with severe microbial keratitis who underwent ocular ultrasonography for possible endophthalmitis at our institution over a 5-year period. Ocular and medical history, ocular examination findings, microbiology results, and ultrasonographic features were collected. RESULTS: Of the 81 included eyes, 15 were diagnosed with endophthalmitis based on clinical findings and evidence of vitritis on ultrasound. Historical factors and physical examination findings more common in the endophthalmitis group than the keratitis-only group include presenting vision of light perception or no light perception (73.3% vs. 31.8%, P = 0.003), history of cataract surgery (80.0% vs. 45.5%, P = 0.02), and full thickness ulcer or perforation (33.3% vs. 9.1%, P = 0.03). Gram-positive organisms were more common in the endophthalmitis group (60.0% vs. 30.3%, P = 0.04). Ultrasound findings of choroidal thickening and retinal detachment were more common in the endophthalmitis group (26.7% vs. 3.4%, P = 0.01 and 13.3% vs. 8.4%, P = 0.04) in addition to the expected preponderance of membranous and dispersed vitreous opacities in that group. Final visual acuity was worse in the endophthalmitis group (2.3 vs. 3.5 LogMAR, P = 0.02). CONCLUSIONS: Diagnosing endophthalmitis can be difficult in eyes with advanced microbial keratitis, and the visual outcomes are often extremely poor. Clinicians should have a particularly high index of suspicion in eyes presenting with light perception or no light perception vision, history of cataract extraction, full thickness ulcer or perforation, or choroidal thickening or retinal detachment on ultrasound.

Effect of Low-Sodium versus Conventional Sodium Dialysate on Left Ventricular Mass in Home and Self-Care Satellite Facility Hemodialysis Patients: A Randomized Clinical Trial.

BACKGROUND: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. METHODS: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. RESULTS: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. CONCLUSIONS: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.

Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) for Visual Rehabilitation in Limbal Stem Cell Deficiency.

OBJECTIVES: To evaluate the clinical outcomes of patients with limbal stem cell deficiency (LSCD) who were fitted with the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral device. METHODS: In this retrospective, interventional case series, we reviewed the charts of 31 eyes of 19 consecutive patients clinically diagnosed with LSCD who were evaluated for the PROSE device. Clinical data were reviewed before PROSE evaluation and at the last available follow-up. The main outcomes measures were best-corrected distance visual acuity (CDVA) and modified ocular involvement score (OIS), graded using a previously described system for corneal findings. RESULTS: Corrected distance visual acuity improved from 0.86±0.50 logarithm of the minimal angle of resolution (Snellen equivalent, 20/145) at baseline to 0.46±0.44 (Snellen equivalent, 20/58) with PROSE at the last follow-up (mean, 25.1±18.0 months; P<0.0001). In 27 eyes (87.1%) CDVA improved, with 22 eyes (71.0%) gaining 2 or more lines of Snellen acuity. When categorized by disease severity, CDVA improved in less severe eyes (stage 1) and more severe eyes (stage 2 or 3; P=0.049 and P=0.00009, respectively). Total OIS was not significantly different between baseline and last follow-up (P=0.754); however the epithelial defect score was significantly less (P=0.034). Twenty-four of 31 eyes (77.4%) continued wearing the PROSE device, with a mean daily wearing time of 10.0±4.6 hrs. CONCLUSIONS: In patients with LSCD, vision improved and the OIS remained stable with PROSE, suggesting that the device could be considered for visual rehabilitation in this population.

Another Classification of First Metatarsophalangeal Joint Dislocation-Type 3: Review and Case Description of the Plantar Dislocation.

Plantar dislocation of the first metatarsophalangeal joint is a possible, albeit rare, injury to the foot. The mechanism has been attributed to a hyperflexion motion, with the hallux situated plantar to the first metatarsal head. In this article, we provide a case example of an open, plantar dislocation of the first metatarsophalangeal and perform a literature review of this rare injury. Based on x-ray analysis of the published cases, the sesamoids may or may not dislocate with the phalanx based off of the local capsuloligamentous anatomy. As a result, a modified Jahss classification (type 3A and type 3B) has been proposed to amend the existing system, adding plantar dislocations of the first metatarsophalangeal without (type 3A) and with (type 3B) sesamoid dislocation.

Long-term outcomes of penetrating keratoplasty for corneal complications of herpes zoster ophthalmicus.

BACKGROUND/AIM: To review the long-term outcomes of penetrating keratoplasty (PKP) for corneal complications of herpes zoster ophthalmicus (HZO). METHODS: We reviewed the medical records of 53 eyes of 53 patients who underwent PKP due to corneal complications of HZO at the Kellogg Eye Center. RESULTS: The mean age of patients at the time of PKP was 68.0±16.4 years, with a follow-up of 4.0±3.8 years and quiescent period of 6.5±5.3 years from active HZO to PKP. Preoperatively, 25 (47.2%) eyes were completely anaesthetic, while 16 (30.2%) had deep corneal neovascularisation in four quadrants. Comorbid ocular disease, including cataract, glaucoma and macular disease, was present in 25 (47.2%) eyes. Twenty patients (37.8%) received acyclovir for the entire postoperative period. There were no recurrences of zoster keratitis in any eye. The most common complications were difficulty healing the ocular surface (12/53, 22.6%) and glaucoma (14/53, 26.4%). Thirty per cent of the eyes required one or more additional postoperative procedures, most commonly tarsorrhaphy (10/53, 18.9%) and amniotic membrane graft (6/53, 11.3%). At 1, 2-4 and ≥5 years, 94%, 82% and 70% grafts remained clear, respectively. Visual acuity improved at 1 year postoperatively (p<0.0001), but this improvement was not sustained. There was no significant benefit of long-term acyclovir on visual acuity (p=0.2132) or graft survival (p=0.241). CONCLUSIONS: Even in eyes with significant preoperative risk factors, PKP for the corneal complications of HZO can achieve favourable tectonic and visual results. Although most grafts remained clear, long-term visual potential may be limited by comorbid ocular diseases. Prophylactic postoperative oral acyclovir did not improve outcomes.

Pharmacokinetics of metformin in patients with chronic kidney disease stage 4 and metformin-naïve type 2 diabetes.

The pharmacokinetics of metformin therapy in patients with chronic kidney disease stage 4 (CKD-4) were studied using data from the largest Phase I consecutive cohort trial yet performed in this population. Eighteen metformin-naïve men and women with Type 2 Diabetes and creatinine clearance (CrCl) in the range 18-49 mL/min (eGFR 15-29 mL/min/1.73 m2) were allocated to daily immediate-release metformin of 250 mg, 500 mg, or 1000 mg. A first-dose profile and trough concentrations for 4 weeks were taken on all patients. Pharmacokinetic (PK) parameters were estimated by fitting a first-order compartment model with absorption in a peripheral compartment to concentrations measured 24 hours post-first dose. Single-dose PK parameters time to maximum concentration (tmax) and maximum concentration (Cmax) were consistent with previous observations in patients with normal renal function (healthy and diabetic), as was the association between CrCl and apparent total oral clearance (Cl/F). However, patients with a CrCl below 32 mL/min had trough concentrations that were consistently above the steady-state minimum implied by the population PK model. This suggests the model may not apply to patients with CrCl below 32 mL/min. Metformin in doses of 500-1000 mg/day could be taken by CKD-4 patients. However, the single-compartment model breaks down as CrCl declines below 32 mL/min suggesting that metformin levels should be monitored regularly in progressive stage 4 CKD.

The Ring Verruca Plantaris in Cantharidin Use A Case Report.

Verrucae (warts) are the most common viral infections of the skin, affecting 7% to 10% of the general population. Typically caused by human papillomavirus type 1, plantar warts manifest as benign proliferation of the epithelial cells on the feet. It has been cited that up to one-third of nongenital warts become recalcitrant, and biopsy is often required to confirm diagnosis and direct appropriate treatment. These treatments can vary from various types of oral medications, acids, ablative modalities, and injections. In this article, we present a case of a recalcitrant plantar wart that appeared to circumferentially spread from the initial site after first-line treatment and presumed resolution with the product cantharidin. The development of ring warts is a known complication associated with cantharidin use, with little described rationale to the presentation.

Defining Talar Head and Neck Pathology: The Malvern Classification System.

Talar fractures account for <1% of all fractures in the body and 3% to 6% of pedal fractures. Of these fractures, avulsion and neck fractures represent the most and second most common type, respectively. Several classification systems exist for talar fractures of the talar dome (Berndt-Hardy), talar neck dislocation (Hawkins), and talar body (Sneppen) anatomic locations. Although diverse, they are not all encompassing for fracture patterns of the talus. Another set of pathologic issues occur about the talar head and neck region that can be seen in the clinical setting. Thus, a new classification system (Malvern classification system for talar head/neck fractures) was devised and defined for this location. The system represents a comprehensive review of the available published data and synthesis into an organized classification system.

The Rare Lesser Metatarsal Bipartite Sesamoid A Case Report.

Sesamoid bones and accessory ossicles are common incidental findings on radiographs. These can occasionally become symptomatic, usually after a precipitating event such as an injury or overuse, or they can be incidental findings unrelated to the presenting pathology. The aim of this study was to highlight a rare case of a bipartite fifth metatarsal sesamoid bone and to review previous literature regarding sesamoid bones and accessory ossicles.