Symptomatic cystic lesions of the talus are rare. The traditional operations usually do not provide visualization to reveal the deep structure of the lesion and could cause cartilage damage or other severe traumatic injury. We report an operative technique to reach the cystic lesion without talar cartilage damage, remove the lesion, and fill defect with a bone graft assisted by anterior arthroscopy and evaluate its safety and reliability for future study. Seven cases of talar bone cyst were included. The patients were placed in the supine position after anesthesia induction and noninvasive ankle traction was applied. Standard anteromedial and anterolateral portals were established to observe the ankle; the distal end of the medial approach was moderately enlarged to 2 to 3 cm. The biopsy specimen of the cyst was obtained under arthroscopic guidance; the cyst wall was abraded and the sclerotic rim drilled. Arthrocare radiofrequency ablation was performed to prevent recurrence. The defect was tightly impacted with autologous or allograft cancellous bone. All cysts in these cases were located in the medial talus; anteroposterior radiographs and computed tomographic coronary scan showed a cyst diameter of >1?cm. Intraoperative inspection showed a tiny chondral gap on the talar dome in 1 case and on the medial wall of talus in 1 case; no cartilage injury was found in the remainder. Two cases were impacted with grafted autogenous iliac bone into the talar defect and 5 cases with allograft cancellous bone. Computed tomography confirmed that the cysts had healed, with no signs of recurrence found in any patient at 1 year postoperatively. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot scale score increased from 65 preoperatively to 91 points postoperatively, a statistically significant difference (p?<?.01). No complications developed and no reoperations were required postoperatively. Arthroscopically assisted anterior treatment with autologous or allograft bone graft is an effective method for symptomatic large talar bone cysts. 相似文献
Traumatic loss of the whole talus is extremely rare, and its possible treatment options are limited. Our experience of treatment of a 30-year-old male suffering from traumatic loss of the whole talus with the insertion of an anatomical antibiotic-loaded talus cement spacer using 3-dimensional printing techniques as an interim measure was reviewed and reported. A young motorcyclist was brought to the emergency department after a road traffic accident. He sustained multiple injuries including traumatic loss of his left talus. Despite repeated surgeries of debridement and insertion of external fixator to his injured ankle, the patient had residual problem of ankle instability, ankle infection, and absence of his involved talus. With the help of computerized 3-dimensional printing techniques, an anatomical talus cement spacer was produced in the operating room and inserted into the patient's ankle 7 weeks after the initial trauma. The external fixator was kept for another 3 weeks before removal. At 14 months after the insertion of cement spacer, the patient could walk independently without any pain for 15 minutes with the help of a crutch occasionally. However, the range of motion of his left ankle was limited to 15° in the flexion-extension arc and minimal subtalar motion. The infection of the left ankle was under control. 相似文献
There were increased reports of fevers and febrile reactions in young children (particularly children aged <5?years) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively.
Methods
For each study, fever rates (any grade and severe) were determined for the following age subgroups (as applicable), using the fever intensity grading system used in the S-IIV3/S-IIV4 studies: 6?months to <3?years; 3 to <5?years; 5 to <9?years; and 9 to <18?years.
Results
For each age subgroup, the any grade and severe fever rates were lower in the S-IIV3/S-IIV4 studies than in the historical IIV3 formulation studies, with the greatest differences in fever rates observed in the youngest age groups. In the 6?months to <3?years group, the any grade fever rate was 7.0% (severe fever: 2.5%) in one S-IIV4 study compared with 38.7% to 40.0% (severe fever: 9.6% to 17.8%) in the historical IIV3 formulation studies. In the 3 to <5?years subgroup, the any grade fever rate was 4.9% (severe fever: 1.2%) in one S-IIV4 study compared with 34.1% to 36.0% (severe fever: 6.3% to 16.5%) in the historical IIV3 formulation studies.
Conclusion
This analysis provides clinical evidence that the modified manufacturing process improved the fever profile across all pediatric age groups, in particular, in children aged <5?years. 相似文献
BackgroundIn May 2014, a mass vaccination campaign with four-component meningococcal serogroup B (4CMenB) vaccine was launched in a localized region of Quebec, Canada experiencing high invasive meningococcal B disease endemicity. Active post-marketing surveillance identified several cases of nephrotic syndrome (NS) among ∼49,000 vaccinated individuals aged 2 months to 20 years. We report the epidemiologic investigation of this potential vaccine safety signal.MethodsActive vaccine safety surveillance was conducted electronically, with participants completing an online questionnaire prompted at 7 days after each dose and 6 months following the last dose. Additional NS cases were sought from provincial hospitalization and emergency room databases.ResultsIn the year following the first dose of 4CMenB vaccination, four confirmed NS cases (three hospitalized) were identified among vaccinated children 2–5-years-old with onset several months post-vaccination. None had renal biopsy but given their age, and positive response to steroids, idiopathic NS was presumptively diagnosed. Among vaccinated children 1–9-years-old, the NS incidence in the year post-vaccination was 17.7 per 100,000 (1 per 5650 vaccinees) with an NS hospitalization rate (i.e. excluding the outpatient case) that was 3.6-fold higher (95%CI = 0.7–11.8; p = 0.12) than the rest of the province for the same period, and 8.3-fold greater (95%CI = 1.1–62.0; p = 0.039) than during the eight years preceding the immunization campaign in the affected region.ConclusionActive safety surveillance identified an unexpected increase in NS incidence following 4CMenB vaccination. Further epidemiological investigation identified four vaccinated cases in total over a 12 month period of follow up. The greater risk in vaccinees had wide confidence intervals with he lower limit including or just above the nul value, an observation with no or marginal statistical significance. The temporal association with vaccination may be explained by other causes and/or chance clustering of a rare event unrelated to vaccination. To confirm or refute a potential link to vaccination, surveillance in other jurisdictions administering 4CMenB to children 1–9-years-old is needed. 相似文献
Live attenuated viral vaccine/vector candidates are inherently unstable and infectivity titer losses can readily occur without defining appropriate formulations, storage conditions and clinical handling practices. During initial process development of a candidate vaccine against HIV-1 using a recombinant Human Cytomegalovirus vector (rHCMV-1), large vector titer losses were observed after storage at 4 °C and after undergoing freeze-thaw. Thus, the goal of this work was to develop candidate frozen liquid formulations of rHCMV-1 with improved freeze-thaw and short-term liquid stability for potential use in early clinical trials. To this end, a virus stability screening protocol was developed including use of a rapid, in vitro cell-based immunofluorescence focus assay to quantitate viral titers. A library of ∼50 pharmaceutical excipients (from various known classes of additives) were evaluated for their effect on vector stability after freeze-thaw cycling or incubation at 4 °C for several days. Certain additives including sugars and polymers (e.g., trehalose, sucrose, sorbitol, hydrolyzed gelatin, dextran 40) as well as removal of NaCl (lower ionic strength) protected rHCMV-1 against freeze-thaw mediated losses in viral titers. Optimized solution conditions (e.g., solution pH, buffers and sugar type) slowed the rate of rHCMV-1 titer losses in the liquid state at 4 °C. After evaluating various excipient combinations, three new candidate formulations were designed and rHCMV-1 stability was benchmarked against both the currently-used and a previously reported formulation. The new candidate formulations were significantly more stable in terms of reducing rHCMV-1 titer losses after 5 freeze-thaw cycles or incubation at 4 °C for 30 days. This case study highlights the utility of semi-empirical design of frozen liquid formulations of a live viral vaccine candidate, where protection against infectivity titer losses due to freeze-thaw and short-term liquid storage are sufficient to enable more rapid initiation of early clinical trials. 相似文献
Diabetes mellitus is a chronic metabolic disorder that has a complex molecular and cellular pathophysiology, resulting in its dynamic progression and that may show differing responses to therapy. The incidence of diabetes mellitus increases with age and requires additive therapeutic agents for its management. SGLT2i and DPP-4 inhibitors and GLP-1 receptor agonists (GLP-1RA) are newly introduced antidiabetic drugs that work through differing mechanisms; DPP-4 inhibitors maintain the endogenous level of GLP1; GLP-1RA result in pharmacological levels of GLP1, whilst SGLT2i act on the proximal tubules of the kidney. They have shown efficacy in the management of diabetes and in contrast to other antidiabetic drugs, do not inherently cause hypoglycemia in therapeutic doses. Autophagy as a highly conserved mechanism to maintain cell survival and homeostasis by degradation of damaged or aged organelles and components, and recognised to be increasingly important in diabetes. In the present review, we discuss the modulatory effects of these newly introduced antidiabetic drugs on the autophagy process. 相似文献
Necrotizing enterocolitis (NEC) is a devastating disease of prematurity that develops after feeding, often without warning, and results in diffuse intestinal necrosis leading to sepsis and death in many cases. The lack of improvement in overall survival is influenced by nonspecific diagnostic modalities as well as inexact and nonpersonalized treatment strategies.
Methods/Results
Recently, we and others have shown that NEC develops in response to exaggerated bacterial signaling in the premature intestine, as a consequence of elevated expression and activity of the bacterial receptor toll-like receptor 4 (TLR4), which is important for normal gut development. Breast milk is a powerful TLR4 inhibitor, while mutations in TLR4 genes lead to increased NEC risk in humans, providing proof-of-concept for its role in NEC. Recently, a drug discovery approach has revealed a novel class of TLR4 inhibitors which are being developed for personalized approaches to NEC treatment.
Conclusion
This review will highlight the current understanding of the role of bacterial signaling in NEC pathogenesis, and will describe advances in diagnosis, prevention and treatment of NEC that may hopefully improve survival for these most fragile patients.
Background: Corneal Dystrophy and Perceptive Deafness (CDPD) or Harboyan syndrome is an autosomal recessive rare disorder, characterized by congenital corneal opacities and progressive sensorineural hearing loss, which usually begins after the second decades of life. This study reports the ophthalmic, audiological and genetic features, in five CDPD affected patients from three Chilean families.
Materials and Methods: Five individuals affected with CDPD from three unrelated Chilean families were clinically and genetically examined. To evaluate a putative founder mutation 7 SNPs were analyzed in the three families, an Argentinian patient (carrier of the same mutation previously reported) and 87 Chilean controls.
Results: The ophthalmic symptoms in the five patients were bilateral and symmetric, starting before one year of age, and visual acuity varied from 0.1 to 0.3. In all cases, hearing loss began over 8 years old. The sequence of the 19 exons of SLC4A11 gene of all the affected patients exhibited homozygous eight nucleotide sequence duplication (c.2233_2240dup TATGACAC, p.(Ile748Metfs*5)) at the end of exon 16. All the affected patients of the three families were homozygous for a haplotype composed of five SNPs and covering 4,1 Mb. The same haplotype was present in one allele of the heterozygous Argentinean patient and has a frequency of 2.76% in Chilean population.
Conclusions: The five CDPD patients were homozygous for the same mutation in the SLC4A11 gene. Haplotype analysis of all the affected, including the case reported from Argentina was in accordance with a founder mutation. 相似文献