Pulmonary tuberculosis in intensive care setting, with a focus on the use of severity scores, a multinational collaborative systematic review.

BACKGROUND AND AIM: Tuberculosis (TB) is associated with a high mortality in the intensive care unit (ICU), especially in subjects with Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation. Despite its global burden on morbidity and mortality, TB is an uncommon cause of ICU admission, however mortality is disproportionate to the advances in diagnosis and treatment made. Herein we report a systematic review of published studies. METHODS: Our Literature search was conducted to identify studies on outcomes of individuals with TB admitted to ICU. We report and review in-hospital mortality, predictors of poorer outcomes, usefulness of severity scoring systems and potential benefits of intravenous antibiotics. Searches from Pubmed, Embase, Cochrane and Medline were conducted from inception to March 2020. Only literature in English was included. RESULTS: Out of 529 potentially relevant articles, 17 were included. Mortality across all studies ranged from 29-95% with an average of 52.9%. All severity scores underestimated average mortality. The most common indication for ICU admission was acute respiratory failure (36.3%). Negative predictors of outcome included hospital acquired infections, need of mechanical ventilation and vasopressors, delay in initiation of anti-TB treatment, more than one organ failure and a higher severity score. Low income, high incidence countries showed a 23.4% higher mortality rate compared to high income, low TB incidence countries. CONCLUSION: Mortality in individuals with TB admitted to ICU is high. Earlier detection and treatment initiation is needed

Dispersive representation and shape of the Kl3 form factors: robustness

An accurate low-energy dispersive parametrization of the scalar Kpi form factor was constructed some time ago in terms of a single parameter guided by the Callan-Treiman low-energy theorem. A similar twice subtracted dispersive parametrization for the vector Kpi form factor will be investigated here. The robustness of the parametrization of these two form factors will be studied in great detail. In particular the cut-off dependence, the isospin breaking effects and the possible, though not highly probable, presence of zeros in the form factors will be discussed. Interesting constraints in the latter case will be obtained from the soft-kaon analog of the Callan-Treiman theorem and a comparison with the recent tau --> K pi nu_tau data.Comment: 24 pages, 11 figure

Contributions of semi-hadronic states Pγ;Sγ,π+π−γP\gamma;S\gamma, \pi^+\pi^-\gamma to amm of muon, in frames of Nambu-Jona-Lasinio model

We calculate the contribution of semi-hadronic states with pseudoscalar $P=\pi^0, \eta$ and scalar ($\sigma$(550))meson accompanied with real photon as an intermediate state of a heavy photon to the anomalous magnetic moment of muon. We consider the intermediate states with $\pi_0$ and $\sigma$ as a hadrons in frames of Nambu-Jona-Lasinio model. The contribution of $\pi_0\gamma$ state is in agreement with results obtained in previous theoretical considerations as well as with experimental data $a_\mu^{\pi_0\gamma}\approx 4.5 \times 10^{-10}$, besides we estimate $a_{\mu}^{\eta\gamma}=0.7 \times 10^{-10}, a_{\mu}^{\sigma\gamma} \sim 1.5 \times 10^{-11}, a_{\mu}^{\pi^+\pi^-\gamma} \sim 3.2 \times 10^{-10}.$ We discass as well the LbL mechanism with $a_{\mu}^{lbl}=10.5 \cdot 10^{-10}.$Comment: 6 pages, 2 figure

Precise Measurements of Direct CP Violation, CPT Symmetry, and Other Parameters in the Neutral Kaon System

We present precise tests of CP and CPT symmetry based on the full dataset of K to pipi decays collected by the KTeV experiment at Fermi National Accelerator Laboratory during 1996, 1997, and 1999. This dataset contains 16 million K to 2pi0 and 69 million K to pi+pi- decays. We measure the direct CP violation parameter Re(epsilon'/epsilon) = (19.2 pm 2.1)x10-4. We find the KL-KS mass difference Deltam = (5270 pm 12)x10^6 hbar/s and the KS lifetime tauS = (89.62 pm 0.05)x10-12 s. We also measure several parameters that test CPT invariance. We find the difference between the phase of the indirect CP violation parameter, epsilon, and the superweak phase, phi_epsilon - phi_SW = (0.40 pm 0.56) degrees. We measure the difference of the relative phases between the CP violating and CP conserving decay amplitudes for K to pi+pi- (phi+-) and for K to 2pi0 (phi00), Delta phi = (0.30 pm 0.35) degrees. From these phase measurements, we place a limit on the mass difference between K0 and K0bar, DeltaM < 4.8 x 10-19 GeV/c^2 at 95% C.L. These results are consistent with those of other experiments, our own earlier measurements, and CPT symmetry.Comment: 28 pages, 30 figures; removed extra figur

Isolated Hepatocyte Transplantation for Crigler-Najjar Syndrome Type 1:

Crigler-Najjar syndrome type 1 (CN1) is an inherited disorder characterized by the absence of hepatic uridine diphosphoglucuronate glucuronosyltransferase (UDPGT), the enzyme responsible for the conjugation and excretion of bilirubin. We performed allogenic hepatocyte transplantation (AHT) in a child with CN1, aiming to improve bilirubin glucuronidation in this condition. A 9-year-old boy with CN1 was prepared with plasmapheresis and immunosuppression with prednisolone and tacrolimus. When a graft was made available, 7.5 × 10 9 hepatocytes were isolated and infused into the portal vein percutaneously. After 2 weeks phenobarbitone was added to promote the enzymatic activity of UDPGT of the transplanted hepatocytes. Nocturnal phototherapy was continued throughout the studied period. Total bilirubin was considered a reliable marker of allogenic cell function. There was no significant variation of vital signs nor complications during the infusion. Mean ± SD bilirubin level was 530 ± 38 µmol/L before and 359 ± 46 µmol/L after AHT (t-test, p < 0.001). However, the introduction of phenobarbitone was followed by a drop of tacrolimus level with increase of alanine aminotransferase (ALT) and increase of bilirubin. After standard treatment of cellular rejection bilirubin fell again but from then on it was maintained at a greater level. After discharge the patient experienced a further increase of bilirubin that returned to predischarge levels after readmission to the hospital. This was interpreted as poor compliance with phototherapy. Only partial correction of clinical jaundice and the poor tolerability to nocturnal phototherapy led the parents to refuse further hepatocyte infusions and request an orthotopic liver transplant. After 24 months the child is well, with good liver function on tacrolimus and prednisolone-based immunosuppression. Isolated AHT, though effective and safe, is not sufficient to correct CN1. Maintenance of adequate immunosuppression and family compliance are the main factors hampering the success of this procedure

Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV Infection in Chimpanzees

Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to virus had a rapid reduction in viral load to below the limit of detection before rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D) conferring resistance to HCV1 neutralization. Finally, three chronically HCV-infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral load was reduced to below the limit of detection for 21 days in one chimpanzee with rebounding virus displaying a resistance mutation (N417S). The other two chimpanzees had 0.5-1.0 log(10) reductions in viral load without evidence of viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp) demonstrated that the sera from the poorly-responding chimpanzees inhibited the ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the chronically-infected chimpanzees implicated endogenous antibody to E2 and interference with HCV1 neutralization although other factors may also be responsible. These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation

Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

Decoherence and CPT Violation in a Stringy Model of Space-Time Foam

I discuss a model inspired from the string/brane framework, in which our Universe is represented as a three brane, propagating in a bulk space time punctured by D0-brane (D-particle) defects. As the D3-brane world moves in the bulk, the D-particles cross it, and from an effective observer on D3 the situation looks like a ``space-time foam'' with the defects ``flashing'' on and off (``D-particle foam''). The open strings, with their ends attached on the brane, which represent matter in this scenario, can interact with the D-particles on the D3-brane universe in a topologically non-trivial manner, involving splitting and capture of the strings by the D0-brane defects. Such processes are described by logarithmic conformal field theories on the world-sheet. Physically, they result in effective decoherence of the string matter on the D3 brane, and as a result, of CPT Violation, but of a type that implies an ill-defined nature of the effective CPT operator. Due to electric charge conservation, only electrically neutral (string) matter can exhibit such interactions with the D-particle foam. This may have unique, experimentally detectable, consequences for electrically-neutral entangled quantum matter states on the brane world, in particular the modification of the pertinent EPR Correlation of neutral mesons in a meson factory.Comment: 41 pages Latex, five eps figures incorporated. Uses special macro