Study Design
Retrospective cohort study
Objectives
To describe the common types of complications and their risk factors during spine surgery in patients with achondroplasia.
Methods
A retrospective ...review was performed of medical records of adult achondroplasia patients who underwent spine surgery at our institution between 2007 and 2021. Inclusion criteria were achondroplasia and age >16 years. Surgical encounters were evaluated for durotomy, postoperative neurologic deficit, wound compromise, medical complications, and return to the operating room. Statistical analysis included evaluation of relationships across complications and fisher exact test applied to bivariate/categorical variables and t-test/ANOVA for continuous variables. Multivariable analysis using logistic regression was performed to account for patient characteristics
Results
Fifty-five patients with achondroplasia underwent 95 surgeries. Forty-nine percent of the surgeries involved a complication. These included durotomy (33.7%), neurologic deficit (11.6%), wound compromise (6.3%), and other medical complications (6.3%). Thirteen percent of surgeries required return to the operating room. The greatest number of complications occurred in thoracolumbar region (60.0%) compared to cervicothoracic (18.2%) and craniocervical junction (33.3%). Chronologically later surgical encounters had decreased complications and durotomies only occurred in thoracolumbar surgeries (45.7%).
Conclusions
Adult patients with achondroplasia undergoing surgery chronologically later in this set of consecutive patients were at a decreased risk for complications. Thoracolumbar surgeries were at the greatest risk for durotomies. Male sex was a risk factor for durotomy, while age was a risk factor for neurologic deficit. The potential for adverse surgical events should be considered when evaluating patients with achondroplasia for spine surgery.
In superconducting quantum circuits, aluminum is one of the most widely used materials. It is currently also the superconductor of choice for the development of topological qubits. However, ...aluminum‐based devices suffer from poor magnetic field compatibility. Herein, this limitation is resolved by showing that adatoms of heavy elements (e.g., platinum) increase the critical field of thin aluminum films by more than a factor of two. Using tunnel junctions, it is shown that the increased field resilience originates from spin‐orbit scattering introduced by Pt. This property is exploited in the context of the superconducting proximity effect in semiconductor–superconductor hybrids, where it is shown that InSb nanowires strongly coupled to Al/Pt films can maintain superconductivity up to 7 T. The two‐electron charging effect is shown to be robust against the presence of heavy adatoms. Additionally, non‐local spectroscopy is used in a three‐terminal geometry to probe the bulk of hybrid devices, showing that it remains free of sub‐gap states. Finally, it is demonstrated that proximitized semiconductor states maintain their ability to Zeeman‐split in an applied magnetic field. Combined with the chemical stability and well‐known fabrication routes of aluminum, Al/Pt emerges as the natural successor to Al‐based systems and is a compelling alternative to other superconductors, whenever high‐field resilience is required.
In superconducting quantum circuits, aluminum is one of the most widely used materials. Aluminum‐based devices suffer from poor magnetic field compatibility. In this article, this limitation is resolved by showing that adatoms of heavy elements (e.g., platinum) increase the critical field of thin aluminum films by more than a factor of two.
The COVID-19 pandemic has had a range of effects on the environment and particularly on wildlife, through diverse and sometimes contradictory impact pathways. In this study, based on data collected ...among indigenous people and local communities from South America (Colombia, Ecuador, Guyana, and Peru), we investigated changes in the use of wildlife resources for food during the first months of the COVID-19 pandemic. Our study generated unique data collected from 756 households in 60 communities and nine sites. We confirm the hypothesis that wildlife use increased as a short-term response to food insecurity during the pandemic, and fish played a more significant role than wild meat in that endeavor. The increase in wild-meat consumption as a response to food insecurity was conditioned by prices and availability (unsuccessful hunts). Wildlife use did not increase as an alternative means to generate income, because communities were cut off from the market economy for several months. Also, whereas the reliance on wildlife emerged as an immediate solution during the first months of the crisis, longer-term strategies prioritized at household level involved diversifying food sources through domestic meat and crop production. Among all available animal-based proteins, local chicken came just after fish as the animal-based source of protein whose consumption increased the most during the first months of the crisis, as a response to food insecurity. We caution that relying on wildlife as a safety net may constitute a poverty trap in cases where the resource is depleted. Although not specifically studied here, access to land and the transmission of traditional knowledge/skills are possible additional determinants of the role that wildlife may play in times of crisis, and this is proposed as an area for future research. Results also attest to local communities expecting more support from their respective national governments, and confirm results from Walters et al. (2021) that governments were generally absent or unable to react quickly during the pandemic, leaving households (or their local leaders) with the responsibility to innovate with local solutions and pro-actively adapt to the rapid impacts of the crisis.
Inhibitors of the human immunodeficiency virus type 1 (HIV-1) protease have entered clinical study as potential therapeutic agents for HIV-1 infection. The clinical efficacy of HIV-1 reverse ...transcriptase inhibitors has been limited by the emergence of resistant viral variants. Similarly, variants expressing resistance to protease inhibitors have been derived in cell culture. We now report the characterization of resistant variants isolated from patients undergoing therapy with the protease inhibitor MK-639 (formerly designated L-735,524). Five of these variants, isolated from four patients, exhibited cross-resistance to all members of a panel of six structurally diverse protease inhibitors. This suggests that combination therapy with multiple protease inhibitors may not prevent loss of antiviral activity resulting from resistance selection. In addition, previous therapy with one compound may abrogate the benefit of subsequent treatment with a second inhibitor.
To date, numerous inhibitors of the human immunodeficiency virus type 1 protease have been reported, but few have been studied extensively in humans, primarily as a consequence of poor oral ...bioavailability in animal models. L-735,524 represents a class of human immunodeficiency virus type 1 protease inhibitors, termed hydroxyaminopentane amides, that incorporate a basic amine into the hydroxyethylene inhibitor backbone. L-735,524 is a potent inhibitor of virus replication in cell culture and inhibits the protease-mediated cleavage of the viral precursor polyproteins that results in the production of noninfectious progeny viral particles. The compound is effective against viruses resistant to reverse transcriptase inhibitors and is synergistically active when used in combination with reverse transcriptase inhibitors. Most importantly, L-735,524 exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals by using clinically acceptable formulations. Accordingly, the compound was selected for evaluation of safety and pharmacokinetic studies in humans.
Aims/hypothesis
Patients with autoimmune type 1 diabetes transplanted with pancreatic islets to their liver experience significant improvement in quality of life through better control of blood sugar ...and enhanced awareness of hypoglycaemia. However, long-term survival and efficacy of the intrahepatic islet transplant are limited owing to liver-specific complications, such as immediate blood-mediated immune reaction, hypoxia, a highly enzymatic and inflammatory environment and locally elevated levels of drugs including immunosuppressive agents, all of which are injurious to islets. This has spurred a search for new islet transplant sites and for innovative ways to achieve long-term graft survival and efficacy without life-long systemic immunosuppression and its complications.
Methods
We used our previously established approach of islet transplant in the anterior chamber of the eye in allogeneic recipient mouse models and a baboon model of diabetes, which were treated transiently with anti-CD154/CD40L blocking antibody in the peri-transplant period. Survival of the intraocular islet allografts was assessed by direct visualisation in the eye and metabolic variables (blood glucose and C-peptide measurements). We evaluated longitudinally the cytokine profile in the local microenvironment of the intraocular islet allografts, represented in aqueous humour, under conditions of immune rejection vs tolerance. We also evaluated the recall response in the periphery of the baboon recipient using delayed-type hypersensitivity (DTH) assay, and in mice after repeat transplant in the kidney following initial transplant with allogeneic islets in the eye or kidney.
Results
Results in mice showed >300 days immunosuppression-free survival of allogeneic islets transplanted in the eye or kidney. Notably, >70% of tolerant mice, initially transplanted in the eye, exhibited >400 days of graft survival after re-transplant in the kidney without immunosuppression compared with ~30% in mice that were initially transplanted in the kidney. Cytokine and DTH data provided evidence of T helper 2-driven local and peripheral immune regulatory mechanisms in support of operational immune tolerance towards the islet allografts in both models.
Conclusions/interpretation
We are currently evaluating the safety and efficacy of intraocular islet transplantation in a phase 1 clinical trial. In this study, we demonstrate immunosuppression-free long-term survival of intraocular islet allografts in mice and in a baboon using transient peri-transplant immune intervention. These results highlight the potential for inducing islet transplant immune tolerance through the intraocular route. Therefore, the current findings are conceptually significant and may impact markedly on clinical islet transplantation in the treatment of diabetes.
Acute kidney injury (AKI) has increasingly been recognized as an important public health issue due to its rising frequency, its associations with early and late adverse outcomes and its economic ...burden.
Given the importance of determining the available resources to address this serious issue, the AKI Committee of SLANH conducted a survey to obtain information about infrastructure, human resources and equipment devoted to the treatment of AKI in Latin America
A total of 246 units from 14 countries participated in the survey, the majority of them pertaining to nephrology divisions in teaching hospitals. Intermittent hemodialysis was universally performed by all of the units, and less frequently, slow extended dialysis (40%) and continuous renal replacement therapy (23%) were performed. Seventy-nine units (30%) perform peritoneal dialysis, but only 51 (19%) of them reported having treated at least 1 patient with this technique in the last 3 months pre-survey. The vast majority of the units reported adequate water treatment and use of modern filter membranes. Most of the patients received renal replacement therapy (RRT) in the intensive care unit. Specific causes of AKI were reported in different frequencies, with a heterogeneous pattern among the countries. Septic abortion, hemolytic-uremic syndrome, community-acquired diarrhea and leptospirosis were the etiologies most frequently associated with AKI.
To our knowledge, this report was the first available study of the equipment and human resources utilized for RRT in AKI patients in Latin America.
Clinicians are under increasing pressure to transfer inpatients with anorexia nervosa to less intensive treatment early in their hospital course. This study identifies prognostic factors clinicians ...can use in determining the earliest time to transfer an inpatient with anorexia to a day hospital program.
The authors reviewed the charts of 59 female patients with anorexia nervosa who were transferred from 24-hour inpatient care to an eating disorder day hospital program. They evaluated the prognostic significance of a variety of anthropometric, demographic, illness history, and psychometric measures in this retrospective chart review.
Greater risk of day hospital program treatment failure and inpatient readmission was associated with longer duration of illness (for patients who had been ill for more than 6 years, risk ratio = 2.7), amenorrhea (for patients who had this symptom for more than 2.5 years, risk ratio = 5.7), or lower body mass index at the time of inpatient admission (for patients with a body mass index of 16.5 or less, risk ratio = 9.6; for those with a body mass index 75% or less than normal, risk ratio = 7.2) or at the time of transition to the day hospital program (for patients with a body mass index of 19 or less, risk ratio = 3.9; for those with a body mass index 90% or less than normal, risk ratio = 11.7).
Inpatients with anorexia nervosa who have the poor prognostic indicators found in this study are in need of continued inpatient care to avoid immediate relapse and higher cost and longer duration of treatment.
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