Thirty-day mortality of patients with hip fracture during COVID-19 pandemic and pre-pandemic periods: A systematic review and meta-analysis

BACKGROUNDTimely intervention in hip fracture is essential to decrease the risks of perioperative morbidity and mortality. However, limitations of the resources, risk of disease transmission and redirection of medical attention to a more severe infective health problem during coronavirus disease 2019 (COVID-19) pandemic period have affected the quality of care even in a surgical emergency.AIMTo compare the 30-d mortality rate and complications of hip fracture patients treated during COVID-19 pandemic and pre-pandemic times.METHODSThe search of electronic databases on 1^st August 2020 revealed 45 studies related to mortality of hip fracture during the COVID-19 pandemic and pre-pandemic times. After careful screening, eight studies were eligible for quantitative and qualitative analysis of data.RESULTSThe pooled data of eight studies (n = 1586) revealed no significant difference in 30-d mortality rate between the hip fracture patients treated during the pandemic and pre-pandemic periods [9.63% vs 6.33%; odds ratio (OR), 0.62; 95%CI, 0.33, 1.17; P = 0.14]. Even the 30-d mortality rate was not different between COVID-19 non-infected patients who were treated during the pandemic time, and all hip fracture patients treated during the pre-pandemic period (OR, 1.03; 95%CI, 0.61, 1.75; P = 0.91). A significant difference in mortality rate was observed between COVID-19 positive and COVID-19 negative patients (OR, 6.99; 95%CI, 3.45, 14.16; P < 0.00001). There was no difference in the duration of hospital stay (OR, -1.52, 95%CI, -3.85, 0.81; P = 0.20), overall complications (OR, 1.62; P = 0.15) and incidence of pulmonary complications (OR, 1.46; P = 0.38) in these two-time frames. Nevertheless, the preoperative morbidity was more severe, and there was less use of general anesthesia during the pandemic time.CONCLUSIONThere was no difference in 30-d mortality rate between hip fracture patients treated during the pandemic and pre-pandemic periods. However, the mortality risk was higher in COVID-19 positive patients compared to COVID-19 negative patients. There was no difference in time to surgery, complications and hospitalization time between these two time periods.     

Conserved features of intermediates in amyloid assembly determine their benign or toxic states

Some amyloid-forming polypeptides are associated with devastating human diseases and others provide important biological functions. For both, oligomeric intermediates appear during amyloid assembly. Currently we have few tools for characterizing these conformationally labile intermediates and discerning what governs their benign versus toxic states. Here, we examine intermediates in the assembly of a normal, functional amyloid, the prion-determining region of yeast Sup35 (NM). During assembly, NM formed a variety of oligomers with different sizes and conformation-specific antibody reactivities. Earlier oligomers were less compact and reacted with the conformational antibody A11. More mature oligomers were more compact and reacted with conformational antibody OC. We found we could arrest NM in either of these two distinct oligomeric states with small molecules or crosslinking. The A11-reactive oligomers were more hydrophobic (as measured by Nile Red binding) and were highly toxic to neuronal cells, while OC-reactive oligomers were less hydrophobic and were not toxic. The A11 and OC antibodies were originally raised against oligomers of Aβ, an amyloidogenic peptide implicated in Alzheimer's disease (AD) that is completely unrelated to NM in sequence. Thus, this natural yeast prion samples two conformational states similar to those sampled by Aβ, and when assembly stalls at one of these two states, but not the other, it becomes extremely toxic. Our results have implications for selective pressures operating on the evolution of amyloid folds across a billion years of evolution. Understanding the features that govern such conformational transitions will shed light on human disease and evolution alike.     

Impact of COVID-19 pandemic and national lockdown on ocular trauma at a tertiary eye care institute

Purpose:To evaluate the impact of the COVID-19 pandemic and the national lockdown on the demographic and clinical profile of patients presenting with ocular trauma.Methods:In this retrospective, hospital-based, comparative analysis, patients presenting to the emergency department with ocular trauma in the following COVID-19 period (March 25, 2020 to July 31, 2020) were compared with patients in the pre-COVID-19 period (March 25, 2019 to July 31, 2019).Results:Overall, 242 patients (COVID-19 period: 71 and pre-COVID-19 period: 171) presented with ocular trauma. The mean age of the patients in COVID-19 and pre-COVID-19 periods were 26.7 ± 17.3 and 34.1 ± 20.3 years, respectively (P = 0.008). A majority of patients (68.6%) in both groups were from the rural background. Home-related injuries were common in the COVID-19 period (78.8%) as compared to pre-COVID-19 period (36.4%) (P < 0.0001). Iron particles (29.5%) were the common inflicting agents in the COVID-19 period while it was plant leaves (25.5%) in the pre-COVID-19 period. The most common ocular diagnosis was open globe injury (40.8%) in the COVID-19 period and microbial keratitis (47.9%) in the pre-COVID-19 period. Surgical intervention was required in 46.4% of patients in the COVID-19 period and 32.1% of patients in the pre-COVID-19 period (P = 0.034).Conclusion:During the COVID-19 period, there was a significant decline in the number of patients presenting with ocular trauma. In this period, a majority of patients sustained ocular trauma in home-settings. About half the patients required surgical intervention which was most commonly rendered in the form of primary wound repair.     

Role of Chemistry and Crystal Structure on the Electronic Defect States in Cs-Based Halide Perovskites

The electronic structure of a series perovskites ABX₃ (A = Cs; B = Ca, Sr, and Ba; X = F, Cl, Br, and I) in the presence and absence of antisite defect X_B were systematically investigated based on density-functional-theory calculations. Both cubic and orthorhombic perovskites were considered. It was observed that for certain perovskite compositions and crystal structure, presence of antisite point defect leads to the formation of electronic defect state(s) within the band gap. We showed that both the type of electronic defect states and their individual energy level location within the bandgap can be predicted based on easily available intrinsic properties of the constituent elements, such as the bond-dissociation energy of the B–X and X–X bond, the X–X covalent bond length, and the atomic size of halide (X) as well as structural characteristic such as B–X–B bond angle. Overall, this work provides a science-based generic principle to design the electronic states within the band structure in Cs-based perovskites in presence of point defects such as antisite defect.     

Recombinant adenoviral vector expressing HCV NS4 induces protective immune responses in a mouse model of Vaccinia-HCV virus infection: A dose and route conundrum

Hepatitis C virus (HCV) leads to chronic infection in the majority of infected patients presumably due to failure or inefficiency of the immune responses generated. Both antibody and cellular immune responses have been suggested to be important in viral clearance. Non-replicative adenoviral vectors expressing antigens of interest are considered as attractive vaccine vectors for a number of pathogens. In this study, we sought to evaluate cellular and humoral immune responses against HCV NS4 protein using recombinant adenovirus as a vaccine vector expressing NS4 antigen. We have also measured the effect of antigen doses and routes of immunization on the quality and extent of the immune responses, especially their role in viral load reduction, in a recombinant Vaccinia-HCV (Vac-HCV) infection mouse model. Our results show that an optimum dose of adenovirus vector (2 × 10⁷ pfu/mouse) administered intramuscularly (i.m.) induces high T cell proliferation, granzyme B-expressing CD8⁺ T cells, pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-2 and IL-6, and antibody responses that can significantly reduce the Vac-HCV viral load in the ovaries of female C57BL/6 mice. Our results demonstrate that recombinant adenovirus vector can induce both humoral and cellular protective immunity against HCV-NS4 antigen, and that immunity is intricately controlled by route and dose of immunizing vector.     

Molecular targeting and treatment of EGFRvIII-positive gliomas using boronated monoclonal antibody L8A4.

PURPOSE: The purpose of the present study was to evaluate a boronated EGFRvIII-specific monoclonal antibody, L8A4, for boron neutron capture therapy (BNCT) of the receptor-positive rat glioma, F98(npEGFRvIII). EXPERIMENTAL DESIGN: A heavily boronated polyamido amine (PAMAM) dendrimer (BD) was chemically linked to L8A4 by two heterobifunctional reagents, N-succinimidyl 3-(2-pyridyldithio)propionate and N-(k-maleimidoundecanoic acid)hydrazide. For in vivo studies, F98 wild-type receptor-negative or EGFRvIII human gene-transfected receptor-positive F98(npEGFRvIII) glioma cells were implanted i.c. into the brains of Fischer rats. Biodistribution studies were initiated 14 days later. Animals received [(125)I]BD-L8A4 by either convection enhanced delivery (CED) or direct i.t. injection and were euthanized 6, 12, 24, or 48 hours later. RESULTS: At 6 hours, equivalent amounts of the bioconjugate were detected in receptor-positive and receptor-negative tumors, but by 24 hours the amounts retained by receptor-positive gliomas were 60.1% following CED and 43.7% following i.t. injection compared with 14.6% ID/g by receptor-negative tumors. Boron concentrations in normal brain, blood, liver, kidneys, and spleen all were at nondetectable levels (<0.5 microg/g) at the corresponding times. Based on these favorable biodistribution data, BNCT studies were initiated at the Massachusetts Institute of Technology Research Reactor-II. Rats received BD-L8A4 ( approximately 40 microg (10)B/ approximately 750 mug protein) by CED either alone or in combination with i.v. boronophenylalanine (BPA; 500 mg/kg). BNCT was carried out 24 hours after administration of the bioconjugate and 2.5 hours after i.v. injection of BPA for those animals that received both agents. Rats that received BD-L8A4 by CED in combination with i.v. BPA had a mean +/- SE survival time of 85.5 +/- 15.5 days with 20% long-term survivors (>6 months) and those that received BD-L8A4 alone had a mean +/- SE survival time of 70.4 +/- 11.1 days with 10% long-term survivors compared with 40.1 +/- 2.2 days for i.v. BPA and 30.3 +/- 1.6 and 26.3 +/- 1.1 days for irradiated and untreated controls, respectively. CONCLUSIONS: These data convincingly show the therapeutic efficacy of molecular targeting of EGFRvIII using either boronated monoclonal antibody L8A4 alone or in combination with BPA and should provide a platform for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors.     

Structure-activity relationships of the antimalarial agent artemisinin. 8. design,synthesis, and CoMFA studies toward the development of artemisinin-based drugs against leishmaniasis and malaria

Artemisinin (1) and its analogues have been well studied for their antimalarial activity. Here we present the antimalarial activity of some novel C-9-modified artemisinin analogues synthesized using artemisitene as the key intermediate. Further, antileishmanial activity of more than 70 artemisinin derivatives against Leishmania donovani promastigotes is described for the first time. A comprehensive structure-activity relationship study using CoMFA is discussed. These analogues exhibited leishmanicidal activity in micromolar concentrations, and the overall activity profile appears to be similar to that against malaria. Substitution at the C-9beta position was shown to improve the activity in both cases. The 10-deoxo derivatives showed better activity compared to the corresponding lactones. In general, compounds with C-9alpha substitution exhibited lower antimalarial as well as antileishmanial activities compared to the corresponding C-9beta analogues. The importance of the peroxide group for the observed activity of these analogues against leishmania was evident from the fact that 1-deoxyartemisinin analogues did not exhibit antileishmanial activity. The study suggests the possibility of developing artemisinin analogues as potential drug candidates against both malaria and leishmaniasis.     

Patterns of self-reported symptoms in pancreatic cancer patients receiving chemoradiation

Pancreatic cancer is a lethal disease characterized by multiple disease-related symptoms. Chemoradiation therapy is a standard of treatment for locally advanced pancreatic cancer. Although shown to prolong survival, there is little information about treatment-related symptoms or the palliative benefits of chemoradiation. We assessed symptoms of patients with locally advanced pancreatic cancer receiving chemoradiation to determine the prevalence, and co-occurrence, of symptoms and to identify the extent to which symptoms interfered with function. Forty-eight patients were treated with chemoradiation on a Phase I protocol. Patients received radiotherapy (50.4 Gy in 28 fractions), capecitabine (median dose 825 mg/m(2) twice daily), and bevacizumab (2.5-10 mg/kg). Symptom severity and its interference with function were prospectively assessed (at presentation, during, and after chemoradiation) in 43 consenting patients using the M.D. Anderson Symptom Inventory. Results showed that 95% of patients reported at least one of the 13 symptoms assessed at presentation. The most commonly reported symptoms of moderate to severe (>or=5 on a 0-10 scale) intensity at presentation were lack of appetite (24%), pain (19%), fatigue (19%), and sleep disturbance (10%). We observed an increase in patients reporting moderate to severe fatigue, nausea, and sleep disturbance during chemoradiation. McNemar tests for paired binary observations showed the proportion of patients reporting moderate to severe symptoms significantly (P<0.001) decreased after chemoradiation at 94 days follow-up (lack of appetite=7%, pain=7%, fatigue=13%, sleep disturbance=7%). This study demonstrates the feasibility and usefulness of symptom assessment in chemoradiation protocols. Future studies with larger cohorts are needed to further characterize multiple symptoms associated with chemoradiation.