The IMPACT study: early loss of skeletal muscle mass in advanced pancreatic cancer patients

Abstract Background Pancreatic cancer (PC) patients have multiple risk factors for sarcopenia and loss of skeletal muscle mass (LSMM), which may cause greater treatment toxicities, reduced response to cancer therapy, prolonged hospitalization, impaired quality of life, and worse prognosis. Methods This is a retrospective study on advanced PC patients treated at the Department of Oncology of Udine, Italy, from January 2012 to November 2017. Among 162 patients who received chemotherapy, 94 consecutive patients with an available computed tomography (CT) scan were retrospectively analyzed. The primary objective of our study was to explore if an early LSMM ≥ 10% (measured at first radiological evaluation and compared with baseline) and/or baseline sarcopenia may impact prognosis. Baseline sarcopenia was defined according to Prado's criteria. Skeletal muscle area was measured as cross‐sectional areas (cm2) using CT scan data through the Picture archiving and communication system (PACS) image system. Results In the whole cohort, 48% of patients were ≤70 years old, and 50% had metastatic disease. At baseline, 73% of patients had sarcopenia, and 16% presented a visceral fat area ≥ 44 cm2/m2. Overall, 21% experienced an early LSMM ≥ 10%. Approximately 33% of sarcopenic patients at baseline and ~35% of patients with early LSMM ≥ 10% had a body mass index > 25 kg/m2. Of note, 71% of patients were evaluated by a nutritionist, and 56% received a dietary supplementation (oral and/or parenteral). After a median follow‐up of 30.44 months, median overall survival (OS) was 11.28 months, whereas median progression‐free survival (PFS) was 5.72 months. By multivariate analysis, early LSMM ≥ 10% was significantly associated with worse OS [hazard ratio (HR): 2.16; 95% confidence interval (CI) 1.23–3.78; P = 0.007] and PFS (HR: 2.31; 95% CI 1.30–4.09; P = 0.004). Moreover, an exploratory analysis showed that inflammatory indexes, such as neutrophil–lymphocyte ratio variation, impact early LSMM ≥ 10% (odds ratio 1.31, 95% CI 1.06–1.61, P = 0.010). Conclusions Early LSMM ≥ 10% has a negative prognostic role in advanced PC patients. Further prospective investigations are needed to confirm these preliminary data

Drug Holidays and Overall Survival of Patients with Metastatic Colorectal Cancer

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni- and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni- and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22–2.32; p = 0.002 and HR,4.89; 95% CI, 3.33–7.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer

Transverse polarisation measurement of Λ\Lambda hyperons in ppNe collisions at sNN\sqrt{s_{NN}}=68.4 GeV with the LHCb detector

A measurement of the transverse polarization of the $\Lambda$ and $\bar{\Lambda}$hyperons in $p$Ne fixed-target collisions at $\sqrt{s_{NN}}$=68.4 GeV is presented using data collected by the LHCb detector. The polarization is studied using the decay $\Lambda \rightarrow p \pi^-$ together with its charge conjugated process, the integrated values measured are $$P_{\Lambda} = 0.029 \pm 0.019 \, (\rm{stat}) \pm 0.012 \, (\rm{syst}) \, ,$$ $$P_{\bar{\Lambda}} = 0.003 \pm 0.023 \, (\rm{stat}) \pm 0.014 \,(\rm{syst}) \,$$ Furthermore, the results are shown as a function of the Feynman $x$ variable, transverse momentum, pseudorapidity and rapidity of the hyperons, and are compared with previous measurements.A measurement of the transverse polarization of the $\Lambda$ and $\bar{\Lambda}$ hyperons in $p$Ne fixed-target collisions at $\sqrt{s_{NN}}$ = 68.4 GeV is presented using data collected by the LHCb detector. The polarization is studied using the decay $\Lambda \rightarrow p \pi^-$ together with its charge conjugated process, the integrated values measured are $$P_{\Lambda} = 0.029 \pm 0.019 \, (\rm{stat}) \pm 0.012 \, (\rm{syst}) \, ,$$ $$P_{\bar{\Lambda}} = 0.003 \pm 0.023 \, (\rm{stat}) \pm 0.014 \,(\rm{syst}) \,.$$ Furthermore, the results are shown as a function of the Feynman~$x$~variable, transverse momentum, pseudorapidity and rapidity of the hyperons, and are compared with previous measurements

Measurement of the branching fraction ratios R(D+)R(D^+) and R(D∗+)R(D^{*+}) using muonic τ\tau decays

The branching fraction ratios of $\kern 0.18em \overline{\kern -0.18em B}{}^0\to D^+\tau^-\overline{\nu}_{\tau}$ and $\kern 0.18em \overline{\kern -0.18em B}{}^0\to D^{*+}\tau^-\overline{\nu}_{\tau}$ decays are measured with respect to their muonic counterparts, using a data sample corresponding to an integrated luminosity of 2.0 fb$^{-1}$ collected by the LHCb experiment in proton-proton collisions at $\sqrt{s} = 13\,\text{TeV}$. The reconstructed final states are formed by combining $D^+$ mesons with $\tau^-\to\mu^-\overline{\nu}_{\mu}\nu_{\tau}$ candidates, where the $D^+$ is reconstructed via the $D^+\to K^-\pi^+\pi^+$ decay. The results are \begin{align*} R(D^{+}) &= 0.249 \pm 0.043 \pm 0.047, \\ R(D^{*+}) &= 0.402 \pm 0.081\pm 0.085, \end{align*} where the first uncertainties are statistical and the second systematic. The two measurements have a correlation coefficient of $-0.39$ and are compatible with the Standard Model.The branching fraction ratios of $\overline{B}^0\to D^+\tau^-\overline{\nu}_{\tau}$ and $\overline{B}^0\to D^{*+}\tau^-\overline{\nu}_{\tau}$ decays are measured with respect to their muonic counterparts, using a data sample corresponding to an integrated luminosity of 2.0 fb$^{-1}$ collected by the LHCb experiment in proton-proton collisions at $\sqrt{s} = 13$ TeV. The reconstructed final states are formed by combining $D^+$ mesons with $\tau^-\to\mu^-\overline{\nu}_{\mu}\nu_{\tau}$ candidates, where the $D^+$ is reconstructed via the $D^+\to K^-\pi^+\pi^+$ decay. The results are \begin{align*} R(D^{+}) &= 0.249 \pm 0.043 \pm 0.047, R(D^{*+}) &= 0.402 \pm 0.081\pm 0.085, \end{align*} where the first uncertainties are statistical and the second systematic. The two measurements have a correlation coefficient of $-0.39$ and are compatible with the Standard Model

Search for the lepton-flavor violating decay Bs0→ϕμ±τ∓B^0_s\to\phi\mu^\pm\tau^\mp

International audienceA search for the lepton-flavor violating decays $B^0_s\to\phi\mu^\pm\tau^\mp$ is presented, using a sample of proton-proton collisions at center-of-mass energies of 7, 8, and 13 TeV, collected with the LHCb detector and corresponding to a total integrated luminosity of $9\,\text{fb}^{-1}$. The $\tau$ leptons are selected using decays with three charged pions. No significant excess is observed, and an upper limit on the branching fraction is determined to be ${\cal B}( B^0_s\to\phi\mu^\pm\tau^\mp) < 1.0\times 10^{-5}$ at 90% confidence level

Comprehensive analysis of local and nonlocal amplitudes in the B0→K∗0μ+μ−B^0 \to K^{*0} \mu^+\mu^- decay

A comprehensive study of the local and nonlocal amplitudes contributing to the decay $B^0\rightarrow K^{*0}(\to K^+\pi^-) \mu^+\mu^-$ is performed by analysing the phase-space distribution of the decay products. The analysis is based on $pp$ collision data corresponding to an integrated luminosity of 8.4fb$^{-1}$ collected by the LHCb experiment. This measurement employs for the first time a model of both one-particle and two-particle nonlocal amplitudes, and utilises the complete dimuon mass spectrum without any veto regions around the narrow charmonium resonances. In this way it is possible to explicitly isolate the local and nonlocal contributions and capture the interference between them. The results show that interference with nonlocal contributions, although larger than predicted, only has a minor impact on the Wilson Coefficients determined from the fit to the data. For the local contributions, the Wilson Coefficient $C_9$, responsible for vector dimuon currents, exhibits a $2.1\sigma$ deviation from the Standard Model expectation. The Wilson Coefficients $C_{10}$, $C_{9}'$ and $C_{10}'$ are all in better agreement than $C_{9}$ with the Standard Model and the global significance is at the level of $1.5\sigma$. The model used also accounts for nonlocal contributions from $B^{0}\to K^{*0}\left[\tau^+\tau^-\to \mu^+\mu^-\right]$ rescattering, resulting in the first direct measurement of the $b s\tau\tau$ vector effective-coupling $C_{9\tau}$.A comprehensive study of the local and nonlocal amplitudes contributing to the decay $B^0\rightarrow K^{*0}(\to K^+\pi^-) \mu^+\mu^-$ is performed by analysing the phase-space distribution of the decay products. The analysis is based on \proton\proton collision data corresponding to an integrated luminosity of 8.4fb$^{-1}$ collected by the LHCb experiment. This measurement employs for the first time a model of both one-particle and two-particle nonlocal amplitudes, and utilises the complete dimuon mass spectrum without any veto regions around the narrow charmonium resonances. In this way it is possible to explicitly isolate the local and nonlocal contributions and capture the interference between them. The results show that interference with nonlocal contributions, although larger than predicted, only has a minor impact on the Wilson Coefficients determined from the fit to the data. For the local contributions, the Wilson Coefficient $C_9$, responsible for vector dimuon currents, exhibits a $2.1\sigma$ deviation from the Standard Model expectation. The Wilson Coefficients $C_{10}$, $C_{9}'$ and $C_{10}'$ are all in better agreement than $C_{9}$ with the Standard Model and the global significance is at the level of $1.5\sigma$. The model used also accounts for nonlocal contributions from $B^{0}\to K^{*0}\left[\tau^+\tau^-\to \mu^+\mu^-\right]$ rescattering, resulting in the first direct measurement of the $b s\tau\tau$ vector effective-coupling $C_{9\tau}$

Search for the lepton-flavor violating decay Bs0→ϕμ±τ∓B_s^0\to \phi \mu^\pm \tau^\mp

A search for the lepton-flavor violating decays $B^0_s\to\phi\mu^\pm\tau^\mp$ is presented, using a sample of proton-proton collisions at center-of-mass energies of 7, 8, and 13 TeV, collected with the LHCb detector and corresponding to a total integrated luminosity of $9\,\text{fb}^{-1}$. The $\tau$ leptons are selected using decays with three charged pions. No significant excess is observed, and an upper limit on the branching fraction is determined to be $\mathcal{B}\left(B^0_s\to\phi\mu^\pm\tau^\mp\right) < 1.0\times 10^{-5}$ at 90% confidence level.A search for the lepton-flavor violating decays $B^0_s\to\phi\mu^\pm\tau^\mp$ is presented, using a sample of proton-proton collisions at center-of-mass energies of 7, 8, and 13 TeV, collected with the LHCb detector and corresponding to a total integrated luminosity of $9\,\text{fb}^{-1}$. The $\tau$ leptons are selected using decays with three charged pions. No significant excess is observed, and an upper limit on the branching fraction is determined to be ${\cal B}( B^0_s\to\phi\mu^\pm\tau^\mp) < 1.0\times 10^{-5}$ at 90% confidence level

Study of b−b-hadron decays to Λc+h−h′−\Lambda_c^+h^-h^{\prime -} final states

Decays of $\Xi_{b}^{-}$ and $\Omega_{b}^{-}$ baryons to $\Lambda_{c}^{+} h^- h^{\prime -}$ final states, with $h^- h^{\prime -}$ being $\pi^{-}\pi^{-}$, $K^{-}\pi^{-}$ and $K^{-}K^{-}$ meson pairs, are searched for using data collected with the LHCb detector. The data sample studied corresponds to an integrated luminosity of $8.7 \rm fb^{-1}$ of $pp$ collisions collected at centre-of-mass energies $\sqrt{s} = 7$, $8$ and $13 \rm TeV$. The products of the relative branching fractions and fragmentation fractions for each signal mode, relative to the $B^{-} \rightarrow \Lambda_{c}^{+} \bar{p} \pi^{-}$ mode, are measured, with $\Xi_{b}^{-} \rightarrow\Lambda_{c}^{+} K^{-} \pi^{-}$, $\Xi_{b}^{-} \rightarrow\Lambda_{c}^{+} K^{-} K^{-}$ and $\Omega_{b}^{-} \rightarrow\Lambda_{c}^{+} K^{-} K^{-}$ decays being observed at over $5\,\sigma$ significance. The $\Xi_{b}^{-} \rightarrow\Lambda_{c}^{+} K^{-} \pi^{-}$ mode is also used to measure the $\Xi_{b}^{-}$ production asymmetry, which is found to be consistent with zero. In addition, the $B^{-} \rightarrow \Lambda_{c}^{+} \bar{p} K^{-}$ decay is observed for the first time, and its branching fraction is measured relative to that of the $B^{-} \rightarrow \Lambda_{c}^{+} \bar{p} \pi^{-}$ mode.Decays of $\Xi_b^-$ and $\Omega_b^-$ baryons to $\Lambda_c^+ h^- h^{\prime -}$ final states, with $h^- h^{\prime -}$ being $\pi^-\pi^-$, $K^-\pi^-$ and $K^-K^-$ meson pairs, are searched for using data collected with the LHCb detector. The data sample studied corresponds to an integrated luminosity of $8.7\,\mathrm{fb}^{-1}$ of $pp$ collisions collected at centre-of-mass energies $\sqrt{s} = 7$, $8$ and $13\,\mathrm{Te\kern -0.1em V}$. The products of the relative branching fractions and fragmentation fractions for each signal mode, relative to the $B^- \to \Lambda_c^+ \overline{p} \pi^-$ mode, are measured, with $\Xi_{b}^- \to\Lambda_{c}^+ K^- \pi^-$, $\Xi_{b}^- \to\Lambda_{c}^+ K^- K^-$ and $\Omega_{b}^- \to\Lambda_{c}^+ K^- K^-$ decays being observed at over $5\,\sigma$ significance. The $\Xi_{b}^- \to\Lambda_{c}^+ K^- \pi^-$ mode is also used to measure the $\Xi_{b}^-$ production asymmetry, which is found to be consistent with zero. In addition, the $B^- \to \Lambda_{c}^+ \overline{p} K^-$ decay is observed for the first time, and its branching fraction is measured relative to that of the $B^- \to \Lambda_{c}^+ \overline{p} \pi^-$ mode

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit