Shahid Husain

Bio: Shahid Husain is an academic researcher from University Health Network. The author has contributed to research in topics: Transplantation & Rietveld refinement. The author has an hindex of 62, co-authored 437 publications receiving 14444 citations. Previous affiliations of Shahid Husain include The Aga Khan University Hospital & St Mary's Hospital.

IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia

Abstract: Emerging evidence supports the concept that T helper type 17 (TH17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the TH17 lineage, and both were crucial for maintaining local control of the Gram-negative pulmonary pathogen, Klebsiella pneumoniae. Although both cytokines regulated CXC chemokines and granulocyte colony–stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury. These data support the concept that the TH17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites.

Infections Due to Scedosporium apiospermum and Scedosporium prolificans in Transplant Recipients: Clinical Characteristics and Impact of Antifungal Agent Therapy on Outcome

Abstract: Background. Unique characteristics, impact of therapy with antifungal agents, and outcome of infections with Scedosporium species were assessed in transplant recipients.Methods. The patients comprised a total of 80 transplant recipients with Scedosporium infections, including 13 patients from our institutions (University of Pittsburgh Medical Center [Pittsburgh, PA], University of Maryland [Baltimore], Duke University Medical Center [Durham, NC], Emory University [Atlanta, GA], and Hospital Gregorio Maranon [Madrid, Spain]) and 67 reported in the literature. The transplant recipients were compared with 190 non—transplant recipients with scedosporiosis who were described in the literature.Results. Overall, 69% of the infections in hematopoietic stem cell transplant (HSCT) recipients and 53% of the infections in organ transplant recipients were disseminated. HSCT recipients, compared with organ transplant recipients, were more likely to have infections caused by Scedosporium prolificans (P = .045), to have an earlier onset of infection (P = .007), to be neutropenic (P < .0001), and to have fungemia (P = .04). Time elapsed from transplantation to Scedosporium infection in transplant recipients has increased in recent years (P = .002). The mortality rate among transplant recipients with scedosporiosis was 58%. In a logistic regression model using amphotericin B as comparison treatment, voriconazole was associated with a trend towards better survival (odds ratio [OR], 10.40; P = .08). Presence of disseminated infection (OR, 0.20; P = .03) predicted lower survival, and receipt of adjunctive surgery as treatment (OR, 5.52; P = .02) independently predicted a better survival in this model.Conclusions. Scedosporium infections in transplant recipients were associated with a high rate of dissemination and a poor outcome overall. The use of newer triazole agents warrants consideration as a therapeutic modality for these infections.

Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome.

Abstract: Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C. neoformans infection in organ transplant recipients.

Risk Factors, Clinical Characteristics, and Outcome of Nocardia Infection in Organ Transplant Recipients: A Matched Case-Control Study

Abstract: Background. Risk factors for Nocardia infection in organ transplant recipients have not been formally assessed in the current era of transplantation.

Opportunistic Mycelial Fungal Infections in Organ Transplant Recipients: Emerging Importance of Non-Aspergillus Mycelial Fungi

Abstract: To determine the spectrum and impact of mycelial fungal infections, particularly those due to non-Aspergillus molds, 53 liver and heart transplant recipients with invasive mycelial infections were prospectively identified in a multicenter study. Invasive mycelial infections were due to Aspergillus species in 69.8% of patients, to non-Aspergillus hyalohyphomycetes in 9.4%, to phaeohyphomycetes in 9.4%, to zygomycetes in 5.7%, and to other causes in 5.7%. Infections due to mycelial fungi other than Aspergillus species were significantly more likely to be associated with disseminated (P=.005) and central nervous system (P=.07) infection than were those due to Aspergillus species. Overall mortality at 90 days was 54.7%. The associated mortality rate was 100% for zygomycosis, 80% for non-Aspergillus hyalohyphomycosis, 54% for aspergillosis, and 20% for phaeohyphomycosis. Thus, non-Aspergillus molds have emerged as significant pathogens in organ transplant recipients. These molds are more likely to be associated with disseminated infections and to be associated with poorer outcomes than is aspergillosis.

IL-17 and Th17 Cells.

Abstract: CD4+ T cells, upon activation and expansion, develop into different T helper cell subsets with different cytokine profiles and distinct effector functions. Until recently, T cells were divided into Th1 or Th2 cells, depending on the cytokines they produce. A third subset of IL-17-producing effector T helper cells, called Th17 cells, has now been discovered and characterized. Here, we summarize the current information on the differentiation and effector functions of the Th17 lineage. Th17 cells produce IL-17, IL-17F, and IL-22, thereby inducing a massive tissue reaction owing to the broad distribution of the IL-17 and IL-22 receptors. Th17 cells also secrete IL-21 to communicate with the cells of the immune system. The differentiation factors (TGF-β plus IL-6 or IL-21), the growth and stabilization factor (IL-23), and the transcription factors (STAT3, RORγt, and RORα) involved in the development of Th17 cells have just been identified. The participation of TGF-β in the differentiation of Th17 cells places ...

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America

Abstract: The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews,” and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.