Injectable and 3D Extrusion Printable Hydrophilic Silicone-Based Hydrogels for Controlled Ocular Delivery of Ophthalmic Drugs.

While silicone elastomers have found widespread use in the biomedical industry, 3D printing them has proven to be difficult due to the material's slow drying time, low viscosity, and hydrophobicity. Herein, we arrested the hydrophilic silicone (HS) macrochains into a semi-interpenetrating polymer network (semi-IPN) via an in situ photogelation-assisted 3D microextrusion printing technique. The flow behavior of the pregel solutions and the mechanical properties of the printed HS hydrogels were tested, showing a high elastic modulus (approximately 15 kPa), a low tan δ, high elasticity, and delayed network rupturing. The uniaxial compression tests demonstrated a nearly negligible permanent deformation, suggesting that the printed hybrid hydrogel maintained its elastic properties. Drug loading and diffusion in the microporous hydrogel are shown via the non-Fickian anomalous transport mechanism, leading to highly tunable loading/releasing profiles (approximately 20% cumulative release) depending on the HS concentration. The drug encapsulation exhibits exceptional stability, remaining intact without any degradation even after a storage period of 1 month. As far as we know, this is the first soft biomaterial based on HS that functions as an exceptional controlled drug delivery device.

Posterior tibialis tendon entrapment as a complication of posterior malleolar fractures in complex ankle fractures.

Aims: Posterior malleolar (PM) fractures are commonly associated with ankle fractures, pilon fractures, and to a lesser extent tibial shaft fractures. The tibialis posterior (TP) tendon entrapment is a rare complication associated with PM fractures. If undiagnosed, TP entrapment is associated with complications, ranging from reduced range of ankle movement to instability and pes planus deformities, which require further surgeries including radical treatments such as arthrodesis. Methods: The inclusion criteria applied in PubMed, Scopus, and Medline database searches were: all adult studies published between 2012 and 2022; and studies written in English. Outcome of TP entrapment in patients with ankle injuries was assessed by two reviewers independently. Results: Four retrospective studies and eight case reports were accepted in this systematic review. Collectively there were 489 Pilon fractures, 77 of which presented with TP entrapment (15.75%). There were 28 trimalleolar fractures, 12 of which presented with TP entrapment (42.86%). All the case report studies reported inability to reduce the fractures at initial presentation. The diagnosis of TP entrapment was made in the early period in two (25%) cases, and delayed diagnosis in six (75%) cases reported. Using modified Clavien-Dindo complication classification, 60 (67%) of the injuries reported grade IIIa complications and 29 (33%) grade IIIb complications. Conclusion: TP tendon was the commonest tendon injury associated with pilon fracture and, to a lesser extent, trimalleolar ankle fracture. Early identification using a clinical suspicion and CT imaging could lead to early management of TP entrapment in these injuries, which could lead to better patient outcomes and reduced morbidity.

Reconstruction of Severe Ankle and Pilon Fracture Malunions.

Malunion of ankle and pilon fractures has significant detrimental effect on function and development of post-trauma osteoarthritis. Unfortunately, the incidence of malunion has been reported to be increasing. It is important to assess the ankle for congruency, because this determines the level where correction will occur. A plethora of techniques are available, with low-level evidence supporting each, and therefore it is important that the treating surgeon is fully prepared and comfortable in the techniques they are to use. Supplementary procedures are common and should be expected. This article provides a review of current methods of treatment and their outcomes.

Posterior Malleolar Ankle Fractures: An Effort at Improving Outcomes.

BACKGROUND: There is increasing acceptance that the clinical outcomes following posterior malleolar fractures are less than satisfactory. We report our results of posterior malleolar fracture management based on the classification by Mason and Molloy. METHODS: All fractures were classified on the basis of computed tomographic (CT) scans obtained preoperatively. This dictated the treatment algorithm. Type-1 fractures underwent syndesmotic fixation. Type-2A fractures underwent open reduction and internal fixation through a posterolateral incision, type-2B fractures underwent open reduction and internal fixation through either a posteromedial incision or a combination of a posterolateral with a medial-posteromedial incision, and type-3 fractures underwent open reduction and internal fixation through a posteromedial incision. RESULTS: Patient-related outcome measures were obtained in 50 patients with at least 1-year follow-up. According to the Mason and Molloy classification, there were 17 type-1 fractures, 12 type-2A fractures, 10 type-2B fractures, and 11 type-3 fractures. The mean Olerud-Molander Ankle Score was 75.9 points (95% confidence interval [CI], 66.4 to 85.3 points) for patients with type-1 fractures, 75.0 points (95% CI, 61.5 to 88.5 points) for patients with type-2A fractures, 74.0 points (95% CI, 64.2 to 83.8 points) for patients with type-2B fractures, and 70.5 points (95% CI, 59.0 to 81.9 points) for patients with type-3 fractures. CONCLUSIONS: We have been able to demonstrate an improvement in the Olerud-Molander Ankle Score for all posterior malleolar fractures with the treatment algorithm applied using the Mason and Molloy classification. Mason classification type-3 fractures have marginally poorer outcomes, which correlates with a more severe injury; however, this did not reach significance. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Early Protected Weightbearing for Acute Ruptures of the Achilles Tendon: Do Commonly Used Orthoses Produce the Required Equinus?

Conservative "functional" management of acute Achilles tendon ruptures has become increasingly popular. Critical to this is the use of the walking orthosis, which positions the ankle in equinus to allow for early weightbearing. Our aim was to test whether 2 common orthoses achieved a satisfactory equinus position. A total of 11 sequentially treated Achilles tendon ruptures were assigned to either a fixed angle walking boot with wedges (FAWW) or an adjustable external equinus-corrected brace (EEB). The lateral radiographs of the cast immobilized tendons showed a mean tibiotalar angle (TTA) of 56° (range 54° to 57°) and a mean tibio-first metatarsal angle (1MTA) of 74° (range 62° to 85°). The FAWW resulted in a mean TTA of 28° (range 15° to 35°) and 1MTA of 37° (range 30° to 45°). The EEB resulted in a TTA of 48° (range 43° to 45°) and 1MTA of 54° (range 47° to 57°). Ankle equinus was significantly greater with the EEB than with the FAWW (p < .05) and similar to that with an equinus cast. The use of wedges produced an equinus appearance through the midfoot but not at the ankle. We express caution in the use of the FAWW because it is unlikely to achieve sufficient ankle equinus to shorten the Achilles tendon.

Stimulants for depression: On the up and up?

The use of traditional psychostimulants (methylphenidate and dexamphetamine) and stimulant-like drugs (modafinil and armodafinil) for the treatment of depression is a growing concern given the lack of research evidence supporting their effectiveness. The current article describes the role of stimulants in treating depression--specifically their risks and benefits and their potential use alongside antidepressants. Clinically, the rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived, and this suggests that they likely operate via different mechanisms to conventional antidepressants. More importantly, there is little evidence from randomised controlled trials supporting their efficacy in treating depression, although modafinil has been shown to be effective in reducing prominent depressive symptoms, such as fatigue. Research is urgently required to clarify psychostimulants' mechanisms of action and to evaluate their long-term benefits and risks in the treatment of major and bipolar depression. Ultimately, specificity of action needs to be determined to inform the sophisticated clinical use of psychostimulants in the management of depression. Until then they should only be prescribed if absolutely necessary, and even then their prescription should be facilitatory and time limited unless it is for investigational purposes.

Chronic Achilles tendon rupture reconstructed using hamstring tendon autograft.

BACKGROUND: Chronic rupture of the Achilles tendon (delayed diagnosis of more than 4 weeks) can result in retraction of the tendon and inadequate healing. Direct repair may not be possible and augmentation methods are challenging when the defect exceeds 5-6 cm, especially if the distal stump is grossly tendinopathic. METHODS: We describe our method of Achilles tendon reconstruction with ipsilateral semitendinosis autograft and interference screw fixation in a patient with chronic rupture, a 9 cm defect and gross distal tendinopathy. RESULTS: Patient reported outcome measures consistently demonstrated improved health status at 12 months post surgery: MOXFQ-Index 38-25, EQ5D-5L 18-9, EQ VAS 70-90 and VISA-A 1-64. The patient was back to full daily function, could single leg heel raise and was gradually returning to sport. No complications or adverse events were recorded. CONCLUSION: Reconstruction of chronic tears of the Achilles tendon with large defects and gross tendinopathy using an ipsilateral semitendinosis autograft and interference screw fixation can achieve satisfactory improvements in patient reported outcomes up to 1 year post-surgery.

Are manic symptoms that 'dip' into depression the essence of mixed features?

BACKGROUND: Three symptoms of (hypo)mania that clinically represent mood disorders mixed states have been omitted from the DSM-5 mixed features specifier because 'they fail to discriminate between manic and depressive syndromes'. Therefore, the present study examined the role of distractibility, irritability and psychomotor agitation (DIP) in characterising mixed depressive states. METHODS: Fifty in-patients at a specialist mood disorders unit underwent a detailed longitudinal clinical evaluation (3-6 weeks) and were assessed on a range of standardized measures to characterise their illness according to depression subtype, duration of illness and clinical features-including specifically depressive and manic symptoms and the context in which these occur. RESULTS: 49 patients met criteria for major depressive episode, and of these, 34 experienced at least one dip symptom. Patients who endorsed distractibility were more likely to be diagnosed with Bipolar Disorder than Major Depressive Disorder; patients who endorsed irritable mood were more likely to have non-melancholic depression (admixture of depressive and anxiety symptoms), and patients who reported psychomotor agitation experienced a significantly greater number of distinct periods of (hypo)manic symptoms compared with those who did not. LIMITATIONS: The present study used a modest sample size and did not control for medication or comorbid illness. Although this is inevitable when examining real-world patients in a naturalistic setting, future research needs to allow for comorbidity and its impact, specifically anxiety. CONCLUSIONS: The present findings suggest that all 3 symptoms that have been excluded from DSM-5 may be cardinal features of mixed states, as they 'dip' into depressive symptoms to create a mixed state.

Dasatinib-induced nephrotic-range proteinuria.

Since the introduction of imatinib, tyrosine kinase inhibition has been a mainstay in the treatment of many malignancies. The number of these medications is growing, as are the number of targeted tyrosine kinases. Off-target effects of these medications can have beneficial or adverse effects on the kidney. The onus of knowing the implications of these medications on kidney function, and appropriate treatment when such adverse effects occur, is on the nephrologist. We present a patient with chronic myelogenous leukemia who developed nephrotic-range proteinuria after initiation on dasatinib therapy that resolved after changing therapy to imatinib. The mechanism of kidney injury caused by dasatinib has not been described previously in the literature. We provide a review of vascular endothelial growth factor and its pharmacologic inhibition as it pertains to kidney pathology and propose possible mechanisms by which dasatinib induces kidney injury.

Solute clearance in CRRT: prescribed dose versus actual delivered dose.

BACKGROUND: Substantial efforts have been made toward defining the dose threshold of continuous renal replacement therapy (CRRT) associated with improved survival in critically ill patients with acute kidney injury. Published studies have used prescribed effluent rates, expressed as total effluent volume (TEV) per weight and unit time (mL/kg/h), as a surrogate for dose. The purpose of this study was to compare differences in CRRT dose based on prescribed effluent rate, measured TEV and direct measurement of urea and creatinine clearance. METHODS: We analyzed data that had been prospectively collected on 200 patients enrolled in a randomized trial comparing survival with a prescribed effluent rate of 20 mL/kg/h (standard dose) to 35 mL/kg/h (high dose) using pre-dilution continuous venovenous hemodiafiltration (CVVHDF). Filters were changed every 72 h. Blood urea nitrogen (BUN), serum creatinine (SCr), effluent urea nitrogen (EUN) and effluent creatinine (ECr) were collected daily. Actual delivered dose was calculated as: (EUN/BUN)*TEV for urea and (ECr/SCr)*TEV for creatinine. Data were available for 165 patients. RESULTS: In both groups, prescribed dose differed significantly from the measured TEV dose (P < 0.001). In the standard dose group, there was no difference between the measured TEV dose and actual delivered urea and creatinine clearances. However, in the high-dose group, measured TEV dose differed significantly from delivered urea clearance by 7.1% (P < 0.001) and creatinine clearance by 13.9% (P < 0.001). CONCLUSIONS: Dose based on prescribed effluent rate or measured TEV is a poor substitute for actual CVVHDF creatinine and urea clearance.

A report on mood and cognitive outcomes with right unilateral ultrabrief pulsewidth (0.3 ms) ECT and retrospective comparison with standard pulsewidth right unilateral ECT.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but its use is limited by the risk of cognitive side effects. This study explored the potential of a novel approach, ultrabrief pulsewidth (0.3 ms) right unilateral (RUL-UB) ECT, to minimise cognitive effects while preserving efficacy. METHODS: Mood and neuropsychological functioning were objectively rated in 30 patients over a course of RUL-UB ECT at 6 times seizure threshold. Results (mood outcomes, ECT treatment parameters) were compared with a retrospectively assessed group of 30 age and gender matched patients who received RUL ECT (1.0 ms pulsewidth, 3.5 times seizure threshold) at the same hospital. RESULTS: Six treatments of RUL-UB ECT resulted in relatively few cognitive side effects, compared to reports of previous studies. The number of responders did not differ between groups but significantly more treatments were required in the RUL-UB group, suggesting a slower speed of response. LIMITATIONS: Patients were not randomised to the two forms of ECT and data was obtained retrospectively in the RUL ECT comparison group. CONCLUSIONS: This study suggests that RUL-UB ECT can be effective in treating depression while incurring lesser cognitive side effects than a commonly used form of RUL ECT, but a greater number of treatments may be required for response.