Osseointegrability of 3D-printed porous titanium alloy implant on tibial shaft bone defect in rabbit model.

Previous studies have demonstrated the ability of osseointegration of porous titanium implants in cancellous bone. Our study was designed to (i) investigate the ability of bone ingrowth into 3D-printed porous titanium alloy implant on the cortical bone of rabbits using CT-scan and histology, and (ii) to identify the consistency of the radiology information between clinical Cone Beam Computed Tomography (CBCT) and Micro Computed Tomography (µCT) in the evaluation of bone ingrowth. The porous titanium alloy implants were 3D-printed employing the Electron Beam Melting (EBM) technology with an intended pore size of 600 µm and porosity of approximately 50 percent. Each implant was inserted into tibial diaphysis in one rabbit and its pores were classified as contacting bone or non-contacting bone. Depending on the time of explantation, the rabbits were divided into two groups: group 1 consisting of 6 rabbits between 13 and 20 weeks and group 2 consisting of 6 rabbits between 26 and 32 weeks. Tissue ingrowth into the non-bone contacting pores were evaluated by CBCT and histology. µCT was used to further investigate the bone ingrowth into four implants (two from each group were randomly chosen). The CBCT detected the present of tissue with bone-like density in both bone-contacting pores and non-bone-contacting pores of all implants. The µCT analysis also supported this result. All the bone-like tissues were then histologically confirmed to be mature bone. The analysis of CBCT data to assess bone ingrowth in porous implants had the sensitivity, specificity, positive and negative predictive values of 85, 84, 93 and 70 percent, respectively, when considering µCT assessment as the gold standard. Fully porous titanium alloy implant has great potential to reconstruct diaphyseal bone defect due to its good ability of osseointegration. CBCT is a promising method for evaluation of bone ingrowth into porous implants.

Fludrocortisone evaluation in aneurysmal subarachnoid hemorrhage patients with cerebral salt wasting (Flush Salt).

OBJECTIVE: Cerebral salt wasting is a condition that can occur in patients with aneurysmal subarachnoid hemorrhage and is characterized by excessive natriuresis, resulting in hyponatremia and hypovolemia. Fludrocortisone is a mineralocorticoid that facilitates retention of sodium and water. Guideline recommendations are weak regarding fludrocortisone use in this patient population due to mixed clinical effectiveness in prior studies. The purpose of this study was to evaluate the clinical effectiveness of fludrocortisone for cerebral salt wasting in patients with aneurysmal subarachnoid hemorrhage. METHODS: This single-site, retrospective study evaluated data from March 29th, 2014 through August 31st, 2021. Patients were included if they were admitted for aneurysmal subarachnoid hemorrhage and received fludrocortisone. Patients were excluded if they were less than 18 years old, pregnant, or received fludrocortisone for less than 48 h. Patients served as their own control and endpoints compared baseline data (24 h prior to fludrocortisone) to a run-in period (0-24-hour post fludrocortisone) and a steady-state period (24-48-hour post fludrocortisone). The primary endpoint was fluid balance, determined by urine output and net daily intake. Secondary endpoints included 3 % hypertonic saline (or equivalent) intake and median serum sodium. RESULTS: There were 110 patients included in this study. Daily doses of fludrocortisone over the 48-hour period varied from 100 mcg to 500 mcg, with 48 % of patients receiving between 200 mcg and 300 mcg daily. Median 24-hour urine output was reduced over the course of the study period (8232 mL at baseline, 8464 mL during 24-hour run-in, and 7080 mL during steady-state timeframe); p = 0.014. There was a 18 % reduction in net volume intake (p = 0.001), including a 38 % reduction in 3 % hypertonic saline (or equivalent) required during the study period; p = 0.025). CONCLUSION: Fludrocortisone was associated with decreased urine output and subsequently, decreased volume intake, to maintain euvolemia in patients with aneurysmal subarachnoid hemorrhage and cerebral salt wasting.

Evaluation of a Series of Wrong Intravitreous Injections.

IMPORTANCE: This case series describes events associated with errors in intravitreous injections. Given the volume of injections performed worldwide, it is important to identify the factors associated with these wrong events to try to reduce their occurrences. OBJECTIVE: To evaluate a series of errors in intravitreous injections within Kaiser Permanente Northern California (KPNC). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective small case series of a convenience sample at KPNC between January 1, 2019, and December 30, 2020, cases of errors in intravitreous injection were identified either as part of a formal institutional quality review or by self-report of the involved surgeon during quality improvement discussions. MAIN OUTCOMES AND MEASURES: Description of the medical errors and the circumstances surrounding these errors. RESULTS: During the 2 years of this evaluation, there were more than 147 000 injections performed within KPNC. Four cases of errors in intravitreous injection were identified. Mistakes were associated with inaccurate review of the electronic medical record, poor surgeon and staff focus, and inconsistent use of surgical checklists and timeouts. No long-term ocular morbidity occurred following any of these errors. CONCLUSIONS AND RELEVANCE: Medical errors related to intravitreous injections have occurred within KPNC. We trust these events are not unique to our practice. A standardized teams-based approach that incorporates rigorous safety protocols will likely be needed to reduce the risk of future wrong intravitreous injections.

Outcomes of prolonged and low-dose ciclosporin in an Asian population.

BACKGROUND: Ciclosporin is used in dermatology for a variety of conditions. Existing guidelines commonly recommend a starting dose of 3-5 mg/kg/day. OBJECTIVES: We sought to assess response in our cohort of patients in whom lower doses of ciclosporin were used, and compare the efficacy and side effect profile with existing literature. METHODS: We retrospectively studied the use of ciclosporin (cyclosporine A) in our dermatological center. Ciclosporin dose trajectories and changes in disease severity were analyzed. RESULTS: 92 patients were studied (64 with eczema, 17 with psoriasis). Mean initiation ciclosporin dose was relatively low at 1.53 mg/kg/day, with an increase to a mean of 2.61 mg/kg/day at 6 months. The median duration of treatment was 180 days (range 3-2160 days, IQR 383). The response was seen as early as 2 weeks, with greatest control of disease at 6 months. 32 patients were on ciclosporin for a period of 1 year or longer, of whom only 1 had a greater than 30% increase in creatinine that crossed the upper limit of normal. CONCLUSION: In our population, a lower dose likely resulted in a slower peak to greatest control, but was well tolerated with minimal renal impairment despite a relatively long average period of use.

Emergent reversal of oral factor Xa inhibitors with four-factor prothrombin complex concentrate.

BACKGROUND: Controversy exists regarding first-line use of the recently approved reversal agent andexanet alfa due to limitations of the ANEXXA-4 study, thrombotic risks, and high medication acquisition cost. The purpose of this study was to evaluate the safety and effectiveness of 4F-PCC for the reversal of emergent oral fXa inhibitor-related bleeding. Furthermore, we aimed to evaluate a subgroup using strict ANNEXA-4 patient selection criteria. METHODS: This was a retrospective study conducted utilizing chart review of adult patients that received 4F-PCC for oral fXa inhibitor-related bleeding. The primary endpoint was the rate of clinical success defined as achieving excellent or good hemostatic effectiveness following the administration of 4F-PCC. Secondary endpoints included in-hospital mortality and arterial/venous thromboembolism, and cost compared with andexanet alfa. RESULTS: A total of 119 patients were included, with 83 patients in the ANNEXA-4 criteria subgroup. Eighty-five of the 119 patients (71%) required reversal due to intracranial bleeding. Prior to reversal, 70 patients (59%) were taking apixaban and 49 patients (41%) were taking rivaroxaban. Clinical success was achieved in 106 of 119 patients (89%) and 74 of 83 patients (90%) in the strict criteria subgroup. Three of 119 patients (2.5%) had a thrombotic event during hospital stay and the overall mortality rate was 13%. The average cost increase of andexanet alfa compared to 4F-PCC would have been $29,500 per patient. CONCLUSIONS: Administration of 4F-PCC for the reversal of oral fXa inhibitors was effective with relatively low thrombotic risk. Further direct prospective comparison of 4F-PCC to andexanet alfa is warranted.

A case of pentosan polysulfate maculopathy originally diagnosed as stargardt disease.

PURPOSE: To describe a patient with a past diagnosis of Stargardt disease that was later determined to be pentosan polysulfate (PPS) maculopathy. OBSERVATIONS: The patient had clinical and imaging findings uncharacteristic of Stargardt disease. Rather, her fundus resembled the recently described maculopathy ascribed to PPS. After genetic testing was found to be negative for pathologic variants, the patient was asked to cease usage of PPS. CONCLUSIONS AND IMPORTANCE: This case emphasizes the importance of reviewing patient medication profiles prior to rendering a diagnosis of a retinal dystrophy. It is essential that ophthalmologists catch drug toxicities as early as possible, to minimize risk of further irreversible vision loss due to continued medication exposure.

Retiform Purpura as a Complication of Microsphere Emboli Following Transarterial Chemoembolization for Primary Hepatocellular Carcinoma: A Case Report and Literature Review.

We report an elderly man with hepatocellular carcinoma who developed a rash after undergoing transarterial chemoembolization (TACE). On examination, there was a reticulated macular pigmentation over the chest and upper abdomen. Skin biopsy revealed foreign material that occluded the small dermal cutaneous vessels. These structures were perfectly spherical, homogeneously eosinophilic, and were also nonrefractile. They had a maximum diameter of 40 µm, consistent with the size of the microspheres used in TACE. TACE is a palliative measure used to treat hepatocellular carcinoma in patients who are not surgical candidates. Vaso-occlusive manifestations of the skin are rare occurrences, with only 8 reported cases. Seven cases attributed this to nontarget embolization of the hepatic falciform artery and 1 case postulated that collateral supply of the targeted area allowed for hematogenous migration of the occluding beads via the microcirculation. Pertaining to treatment, all patients were treated with oral nonsteroidal anti-inflammatory agents to good effect, with 1 patient receiving additional laser treatment and another having local steroid injections. Prognosis is excellent, because the skin lesions tend to resolve within a year. Several methods have been suggested to prevent these vaso-occlusive skin complications, including prophylactic application of ice or placing the tip of the microcatheter distal to the origin of the hepatic falciform artery and falciform artery.

3D imaging of optically cleared tissue using a simplified CLARITY method and on-chip microscopy.

High-throughput sectioning and optical imaging of tissue samples using traditional immunohistochemical techniques can be costly and inaccessible in resource-limited areas. We demonstrate three-dimensional (3D) imaging and phenotyping in optically transparent tissue using lens-free holographic on-chip microscopy as a low-cost, simple, and high-throughput alternative to conventional approaches. The tissue sample is passively cleared using a simplified CLARITY method and stained using 3,3'-diaminobenzidine to target cells of interest, enabling bright-field optical imaging and 3D sectioning of thick samples. The lens-free computational microscope uses pixel super-resolution and multi-height phase recovery algorithms to digitally refocus throughout the cleared tissue and obtain a 3D stack of complex-valued images of the sample, containing both phase and amplitude information. We optimized the tissue-clearing and imaging system by finding the optimal illumination wavelength, tissue thickness, sample preparation parameters, and the number of heights of the lens-free image acquisition and implemented a sparsity-based denoising algorithm to maximize the imaging volume and minimize the amount of the acquired data while also preserving the contrast-to-noise ratio of the reconstructed images. As a proof of concept, we achieved 3D imaging of neurons in a 200-µm-thick cleared mouse brain tissue over a wide field of view of 20.5 mm2. The lens-free microscope also achieved more than an order-of-magnitude reduction in raw data compared to a conventional scanning optical microscope imaging the same sample volume. Being low cost, simple, high-throughput, and data-efficient, we believe that this CLARITY-enabled computational tissue imaging technique could find numerous applications in biomedical diagnosis and research in low-resource settings.

A Fatal Case of "Bullous Erysipelas-like" Pseudomonas Vasculitis.

Erysipelas is a generally benign superficial bacterial skin infection, and its bullous form constitutes a rare and more severe variant. We describe the first and fatal case of "bullous erysipelas-like" septic vasculitis due to Pseudomonas bacteremi. A 69-year-old Chinese man presenting with diarrhea and septic shock initially began to rapidly develop sharply defined erythematous plaques with non-hemorrhagic bullae over his lower limbs. Culture of the aspirate from the bullae was positive for Pseudomonas aeruginosa. This was also consistent with his blood cultures showing Pseudomonas bacteremia. Histology of the skin lesion showed microthrombi and neutrophilic infiltrates in blood vessels with Gram-negative bacilli extruding from the vessel walls, characteristic of septic vasculitis. The bullous erysipelas-like lesions seen in this patient represents a rare manifestation of both septic vasculitis and Pseudomonas infection.

A dramatic presentation of an unusual form of cutaneous lymphoma.

We report an unusual and dramatic presentation of a rare form of cutaneous lymphoma, known as subcutaneous panniculitis-like T-cell lymphoma (SPTCL). This patient presented with a pruritic, florid and purpuric rash that was diagnosed as lobular panniculitis and treated with oral steroids for 1 year with no success. His skin lesions would return each time oral corticosteroids were being weaned off. Upon presentation to our clinic, repeated deep skin biopsies with immunohistochemical analysis coupled with the clinical history of persistent B symptoms and the presence of pancytopenia helped clinched the rare diagnosis of SPTCL with hemophagocytosis. The patient was then started on cyclosporine and dexamethasone before definitive chemotherapy. This rare and diagnostically challenging condition is commonly misdiagnosed as benign panniculitis or eczema, and highlights the importance of repeated skin biopsies.

Characterization of Darai Limestone Composition and Porosity Using Data-Constrained Modeling and Comparison with Xenon K-Edge Subtraction Imaging.

Data-constrained modeling is a method that enables three-dimensional distribution of mineral phases and porosity in a sample to be modeled based on micro-computed tomography scans acquired at different X-ray energies. Here we describe an alternative method for measuring porosity, synchrotron K-edge subtraction using xenon gas as a contrast agent. Results from both methods applied to the same Darai limestone sample are compared. Reasonable agreement between the two methods and with other porosity measurements is obtained. The possibility of a combination of data-constrained modeling and K-edge subtraction methods for more accurate sample characterization is discussed.

Pancreatic panniculitis.

We describe a rare case of a patient with pancreatic adenocarcinoma who presented initially with a rash on her lower legs. Skin biopsy showed lobular panniculitis and characteristic "ghost" adipocytes consistent with pancreatitic panniculitis. This clinical case is an interesting example where a seemingly innocuous skin condition heralds an underlying malignant disease process.

A synchrotron-based local computed tomography combined with data-constrained modelling approach for quantitative analysis of anthracite coal microstructure.

Quantifying three-dimensional spatial distributions of pores and material compositions in samples is a key materials characterization challenge, particularly in samples where compositions are distributed across a range of length scales, and where such compositions have similar X-ray absorption properties, such as in coal. Consequently, obtaining detailed information within sub-regions of a multi-length-scale sample by conventional approaches may not provide the resolution and level of detail one might desire. Herein, an approach for quantitative high-definition determination of material compositions from X-ray local computed tomography combined with a data-constrained modelling method is proposed. The approach is capable of dramatically improving the spatial resolution and enabling finer details within a region of interest of a sample larger than the field of view to be revealed than by using conventional techniques. A coal sample containing distributions of porosity and several mineral compositions is employed to demonstrate the approach. The optimal experimental parameters are pre-analyzed. The quantitative results demonstrated that the approach can reveal significantly finer details of compositional distributions in the sample region of interest. The elevated spatial resolution is crucial for coal-bed methane reservoir evaluation and understanding the transformation of the minerals during coal processing. The method is generic and can be applied for three-dimensional compositional characterization of other materials.