Background. The physical signs of impending death have not been well characterized in cancer patients. A better understanding of these signs may improve the ability of clinicians to diagnose impending death. We examined the frequency and onset of 10 bedside physical signs and their diagnostic performance for impending death. Methods. We systematically documented 10 physical signs every 12 hours from admission to death or discharge in 357 consecutive patients with advanced cancer admitted to two acute palliative care units. We examined the frequency and median onset of each sign from death backward and calculated their likelihood ratios (LRs) associated with death within 3 days. Results. In total, 203 of 357 patients (52 of 151 in the U.S., 151 of 206 in Brazil) died. Decreased level of consciousness, Palliative Performance Scale #20%, and dysphagia of liquids appeared at high frequency and .3 days before death and had

Background Accurate survival prediction is essential for decision-making in cancer therapies and care planning. Objective physiologic measures may improve the accuracy of prognostication. In this prospective study, we determined the association of phase angle, hand grip strength, and maximal inspiratory pressure with overall survival in patients with advanced cancer. Methods We enrolled hospitalized patients with advanced cancer who were seen by palliative care for consultation. We collected information on phase angle, hand grip strength, maximal inspiratory pressure and known prognostic factors including Palliative Prognostic Score (PaP), Palliative Prognostic Index, serum albumin and body composition. We conducted univariate and multivariate survival analysis, and examined the correlation between phase angle and other prognostic variables. Results 222 patients were enrolled: average age 55 (range 22–79), female 59%, mean Karnofsky Performance Status 55, and median overall survival 106 days (95% confidence interval [CI] 71–128 days). The median survival for patients with phase angle 2–2.9°, 3–3.9°, 4–4.9°, 5–5.9° and ≥6° was 35, 54, 112, 134 and 220 days, respectively (P=0.001). In multivariate analysis, phase angle (hazard ratio [HR]=0.86 per degree increase; 95% CI 0.74–0.99; P=0.04), PaP (HR=1.07; 95% CI 1.02–1.13, P=0.008), serum albumin (HR=0.67, 95% CI 0.50–0.91; P=0.009), and fat free mass (HR=0.98, CI=0.96–0.99; P=0.02) were significantly associated with survival. Phase angle was only weakly (γ<0.4) associated with other prognostic variables. Conclusions Phase angle was a novel predictor of poor survival, independent of established prognostic factors in the advanced cancer setting. This objective and non-invasive tool may be useful for bedside prognostication.

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Background We recently reported 5 highly specific physical signs associated with death within 3 days among cancer patients that may aid the diagnosis of impending death. In this study, we examined the frequency and onset of an additional 52 bedside physical signs and their diagnostic performance for impending death. Methods We enrolled 357 consecutive patients with advanced cancer admitted to acute palliative care units at two tertiary care cancer centers. We systematically documented 52 physical signs every 12 hours from admission to death or discharge. We examined the frequency and median time of onset of each sign from death backwards, and calculated their likelihood ratios (LRs) associated with death in 3 days. Results 203/357 (57%) patients died at the end of the admission. We identified 8 physical signs that were highly diagnostic of impending death. These signs occurred in 5-78% of patients in the last 3 days of life, had a late onset, and had a high specificity (>95%) and high positive LR for death within 3 days, including non-reactive pupils (positive LR 16.7, 95% confidence interval 14.9-18.6), decreased response to verbal stimuli (8.3, 7.7-9), decreased response to visual stimuli (6.7, 6.3-7.1), inability to close eyelids (13.6, 11.7-15.5), drooping of nasolabial fold (8.3, 7.7-8.9), hyperextension of neck (7.3, 6.7-8), grunting of vocal cords (11.8, 10.3-13.4), and upper gastrointestinal bleed (10.3, 9.5-11.1). Conclusion We identified 8 highly specific physical signs associated with death within 3 days in cancer patients. These signs may inform the diagnosis of impending death.

Acute lung injuries due to acute lung infections remain a major cause of mortality. Thus a combination of an antibiotic and a compound with immunomodulatory and anti-inflammatory activities can help to overcome acute lung infection-induced injuries. Curcumin derived from the rhizome of turmeric has been used for decades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatory properties by downregulation of various inflammatory mediators. Keeping these properties in mind, we investigated the anti-inflammatory properties of curcumin in a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillation of bacteria in this mouse model of acute pneumonia-induced inflammation resulted in a significant increase in neutrophil infiltration in the lungs along with increased production of various inflammatory mediators [i.e. malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), tumour necrosis factor (TNF)-a] in the lung tissue. The animals that received curcumin alone orally or in combination with augmentin, 15 days prior to bacterial instillation into the lungs via the intranasal route, showed a significant (P ,0.05) decrease in neutrophil influx into the lungs and a significant (P ,0.05) decrease in the production of MDA, NO, MPO activity and TNF-a levels. Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-a levels significantly (P .0.05) as compared to the control group. We therefore conclude that curcumin ameliorates lung inflammation induced by K. pneumoniae B5055 without significantly (P ,0.05) decreasing the bacterial load in the lung tissue whereas augmentin takes care of bacterial proliferation. Hence, curcumin can be used as an adjunct therapy along with antibiotics as an anti-inflammatory or an immunomodulatory agent in the case of acute lung infection.

The urgent need for a cure for early phase COVID-19 infected patients critically underlines drug repositioning strategies able to efficiently identify new and reliable treatments by merging computational, experimental, and pharmacokinetic expertise. Here we report new potential therapeutics for COVID-19 identified with a combined virtual and experimental screening strategy and selected among already approved drugs. We used hydroxychloroquine (HCQ), one of the most studied drugs in current clinical trials, as a reference template to screen for structural similarity against a library of almost 4000 approved drugs. The top-ranked drugs, based on structural similarity to HCQ, were selected for in vitro antiviral assessment. Among the selected drugs, both zuclopenthixol and nebivolol efficiently block SARS-CoV-2 infection with EC 50 values in the low micromolar range, as confirmed by independent experiments. The anti-SARS-CoV-2 potential of ambroxol, amodiaquine, and its active metabolite ( N -monodesethyl amodiaquine) is also discussed. In trying to understand the “hydroxychloroquine” mechanism of action, both p K a and the HCQ aromatic core may play a role. Further, we show that the amodiaquine metabolite and, to a lesser extent, zuclopenthixol and nebivolol are active in a SARS-CoV-2 titer reduction assay. Given the need for improved efficacy and safety, we propose zuclopenthixol, nebivolol, and amodiaquine as potential candidates for clinical trials against the early phase of the SARS-CoV-2 infection and discuss their potential use as adjuvant to the current (i.e., remdesivir and favipiravir) COVID-19 therapeutics.

BackgroundSuccess of biofilm dwelling bacteria in causing persistent and chronic infections is attributed to their resistance towards antibiotics and immune defences. Free iron is critical for the growth of biofilm associated bacteria. Therefore in the present study, the effect of limiting iron levels by addition of divalent Co[II] ions in combination with a bacteriophage was used for preventing/disrupting Klebsiella pneumoniae biofilms.ResultsA significantly higher reduction (p < 0.005) in bacterial numbers in the younger as well as older biofilms treated with Co[II] and depolymerase producing phage in combination was observed in comparison to when either of the agents was used alone. The role of phage borne depolymerase was confirmed, as an insignificant eradication of biofilm by non-depolymerase producing bacteriophage in combination with cobalt ions was observed. The results of viable count were further confirmed by visual examination of biofilms.ConclusionFrom the study it can be concluded, that iron antagonizing molecules and bacteriophages can be used as adjunct therapy for preventing biofilm development.