'To prone or not to prone' in severe ARDS: Questions answered, but others remain

Background\ud Previous trials involving patients with the acute respiratory distress syndrome (ARDS) have failed to show a beneficial effect of prone positioning during mechanical ventilator support on outcomes. We evaluated the effect of early application of prone positioning on outcomes in patients with severe ARDS.\ud \ud Methods\ud Objective: The objective was to evaluate the effect of early application of prone position on mortality in patients with severe ARDS.\ud \ud Design: The PROSEVA group conducted a multicenter, prospective, randomized controlled trial.\ud \ud Setting: Patients with ARDS were recruited from 26 ICUs in France and one ICU in Spain.\ud \ud Subjects: The subjects were critically ill patients admitted to the ICU with respiratory failure requiring mechanical ventilation for severe ARDS. Severe ARDS criteria - an arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio of less than 150 mm Hg, an FiO2 of at least 0.6, a positive end-expiratory pressure of at least 5 cm of water, and a tidal volume of about 6 mL per kilogram of predicted body weight - were confirmed after 12 to 24 hours of mechanical ventilation in the participating ICUs. Subjects were eligible after 12 to 24 hours of stabilization and were randomly assigned to either the prone group or the supine group.\ud \ud Intervention: Four hundred sixty-six patients with severe ARDS underwent prone position ventilation of at least 16 hours or ventilation in the supine position. Patients assigned to the prone group were manually turned in standard ICU beds to the prone position within the first hour of random assignment and were placed prone for at least 16 consecutive hours. Standard ventilator protocols and weaning protocols were implemented for study participants.\ud \ud Outcomes: The primary outcome was the proportion of patients who died from any cause within 28 days after random assignment.\ud \ud Results\ud In total, 237 patients were assigned to the prone group and 229 patients were assigned to the supine group. The 28-day mortality rates were 16% in the prone group and 32.8% in the supine group (P <0.001). The hazard ratio for death with prone ventilation was 0.39 (95% CI 0.25 to 0.63). Unadjusted 90-day mortality rates were 23.6% in the prone group and 41% in the supine group (P <0.001), with a hazard ratio of 0.44 (95% CI 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group.\ud \ud Conclusions\ud In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality

‘Site of contact genotoxicity’ assessment for implants - Potential use of single cell gel electrophoresis in biocompatibility testing of medical devices

Toxicological risk assessment of medical devices requires genotoxicity assessment as per ISO 10993, Part 3, which is designed to address gene mutations, clastogenicity and/or aneugenicity endpoints. ‘Site of contact genotoxicity’ is a potential genotoxic risk especially for medical implants, that is currently not addressed in biocompatibility standards. We therefore performed initial validation study on the use of alkaline single cell gel electrophoresis (comet assay) for detecting ‘site of contact genotoxicity’ of medical devices, using test items made of acrylic implants impregnated with ethyl methanesulphonate (EMS). Comet assay detected increased DNA migration at the site of implantation, but not in the liver. The same implants also failed to show any genotoxicity potentials, when tested on the standard test battery using Salmonella/microsome and chromosome aberration assays. The study suggested that some medical implants can cause ‘site of contact genotoxicity’, without producing systemic genotoxicity. In conclusion, comet assay will add new dimension to safety assessment of medical devices, and this assay can be added to the battery of genetic toxicology tests for evaluating biocompatibility of medical implants

Abelian-Higgs and Vortices from ABJM: towards a string realization of AdS/CMT

We present ans\"{a}tze that reduce the mass-deformed ABJM model to gauged Abelian scalar theories, using the fuzzy sphere matrices $G^\alpha$. One such reduction gives a Toda system, for which we find a new type of nonabelian vortex. Another gives the standard Abelian-Higgs model, thereby allowing us to embed all the usual (multi-)vortex solutions of the latter into the ABJM model. By turning off the mass deformation at the level of the reduced model, we can also continuously deform to the massive $\phi^4$ theory in the massless ABJM case. In this way we can embed the Landau-Ginzburg model into the AdS/CFT correspondence as a consistent truncation of ABJM. In this context, the mass deformation parameter $\mu$ and a field VEV $$ act as $g$ and $g_c$ respectively, leading to a well-motivated AdS/CMT construction from string theory. To further this particular point, we propose a simple model for the condensed matter field theory that leads to an approximate description for the ABJM abelianization. Finally, we also find some BPS solutions to the mass-deformed ABJM model with a spacetime interpretation as an M2-brane ending on a spherical M5-brane.Comment: 43 pages, latex, explanations added in the introduction, end of section 4, and on page 2

A comparison of clinical outcomes between vaccinated and vaccine-naive patients of COVID-19, in four tertiary care hospitals of Kerala, South India

The problem considered: This multi-centric study analyzed data of COVID-19 patients and compared differences in symptomatology, management, and outcomes between vaccinated and vaccine-naive patients. Methods: All COVID-19 positive individuals treated as an in-or out-patient from the 1stMarch to 15th May 2021 in four selected study sites were considered for the study. Treatment details, symptoms, and clinical course were obtained from hospital records. Chi-square was used to test the association of socio-demographic and treatment variables with the vaccination status and binary logistic regression were used to obtain the odds ratio with a 95% confidence interval. Results: The analysis was of 1446 patients after exclusion of 156 with missing data of which males were 57.3% and females 42.7%. 346 were vaccinated; 189 received one dose and 157 both doses. Hospitalization was more in vaccinated (38.2% vs 27.4%); ICU admissions were less in vaccinated (3.5% vs 7.1%). More vaccinated were symptomatic (OR = 1.5); half less likely to be on non-invasive ventilation (OR = 0.5) while vaccine naive patients had 4.21 times the risk of death. Conclusion: Severe infection, duration of hospital stays, need for ventilation and death were significantly less among vaccinated when compared with vaccine naive patients

ABJM Dibaryon Spectroscopy

We extend the proposal for a detailed map between wrapped D-branes in Anti-de Sitter space and baryon-like operators in the associated dual conformal field theory provided in hep-th/0202150 to the recently formulated AdS_4 \times CP^3/ABJM correspondence. In this example, the role of the dibaryon operator of the 3-dimensional CFT is played by a D4-brane wrapping a CP^2 \subset CP^3. This topologically stable D-brane in the AdS_4 \times CP^3 is nothing but one-half of the maximal giant graviton on CP^3.Comment: 26 page

Recurrence of Diabetic Pedal Ulcerations Following Tendo-Achilles Lengthening

Foot and ankle surgeons are frequently challenged by the devastating systemic consequences of diabetes mellitus manifested through neuropathy, integumentary and joint breakdown, delayed healing, decreased ability to fight infection, and fragile tendon/ligaments. Diabetic neuropathic pedal ulcerations lead to amputations at an alarming rate and also carry a high mortality rate. This article will discuss causes of diabetic pedal ulcerations that persist or recur after tendo-Achilles lengthening and will highlight areas that need to be addressed by the practitioner such as infection, vascular and nutritional status, glucose control, off-loading, biomechanics, and patient compliance

Platinum-(IV)-derivative satraplatin induced G2/M cell cycle perturbation via p53-p21(waf1/cip1)-independent pathway in human colorectal cancer cells

Platinum-(IV)-derivative satraplatin represents a new generation of orally available anti-cancer drugs that are under development for the treatment of several cancers. Understanding the mechanisms of cell cycle modulation and apoptosis is necessary to define the mode of action of satraplatin. In this study, we investigate the ability of satraplatin to induce cell cycle perturbation, clonogenicity loss and apoptosis in colorectal cancer (CRC) cells.Platinum-(IV)-derivative satraplatin represents a new generation of orally available anti-cancer drugs that are under development for the treatment of several cancers. Understanding the mechanisms of cell cycle modulation and apoptosis is necessary to define the mode of action of satraplatin. In this study, we investigate the ability of satraplatin to induce cell cycle perturbation, clonogenicity loss and apoptosis in colorectal cancer (CRC) cells

Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom

Background: Real-world data on the efficacy and safety of onasemnogene abeparvovec (OA) in spinal muscular atrophy (SMA) are needed, especially to overcome uncertainties around its use in older and heavier children. This study evaluated the efficacy and safety of OA in patients with SMA type 1 in the UK, including patients ≥2 years old and weighing ≥13.5 kg. / Methods: This observational cohort study used data from patients with genetically confirmed SMA type 1 treated with OA between May 2021 and January 2023, at 6 infusion centres in the United Kingdom. Functional outcomes were assessed using age-appropriate functional scales. Safety analyses included review of liver function, platelet count, cardiac assessments, and steroid requirements. / Findings: Ninety-nine patients (45 SMA therapy-naïve) were treated with OA (median age at infusion: 10 [range, 0.6–89] months; median weight: 7.86 [range, 3.2–20.2] kg; duration of follow-up: 3–22 months). After OA infusion, mean ± SD change in CHOP-INTEND score was 11.0 ± 10.3 with increased score in 66/78 patients (84.6%); patients aged 100 U/L (95% CI, 2.3–223.7; P = 0.008) and 21.2-fold increased odds of steroid doubling, as per treatment protocol (95% CI, 2.2–209.2; P = 0.009) in patients weighing ≥13.5 kg versus <8.5 kg. Weight at infusion was positively correlated with steroid treatment duration (r = 0.43; P < 0.001). Worsening transaminitis, despite doubling of oral prednisolone, led to treatment with intravenous methylprednisolone in 5 children. Steroid-sparing immunosuppressants were used in 5 children to enable steroid weaning. Two deaths apparently unrelated to OA were reported. / Interpretation: OA led to functional improvements and was well tolerated with no persistent clinical complications, including in older and heavier patients. / Funding: Novartis Innovative Therapies AG provided a grant for independent medical writing services

The giant graviton on AdS_{4} x CP^{3} - another step towards the emergence of geometry

We construct the giant graviton on AdS_{4} x CP^{3} out of a four-brane embedded in and moving on the complex projective space. This configuration is dual to the totally anti-symmetric Schur polynomial operator \chi_{R}(A_{1}B_{1}) in the 2+1-dimensional, N = 6 super Chern-Simons ABJM theory. We demonstrate that this BPS solution of the D4-brane action is energetically degenerate with the point graviton solution and initiate a study of its spectrum of small fluctuations. Although the full computation of this spectrum proves to be analytically intractable, by perturbing around a "small'" giant graviton, we find good evidence for a dependence of the spectrum on the size, \alpha_{0}, of the giant. This is a direct result of the changing shape of the worldvolume as it grows in size.Comment: 46 pages, 7 figures. Further details added to section 6 - the solutions to the leading order fluctuation equations and the leading order spectrum have been obtained - and additional comments added to the discussion. Additional references added. Mistake in section 2 correcte