Dynamics of cytomegalovirus-specific T-cell recovery in allogeneic hematopoietic cell transplant recipients using a commercially available flow cytometry assay: A pilot study.

BACKGROUND: Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population. METHODS: In this prospective, observational, pilot study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100. RESULTS: Twenty-eight allo-HCT recipients were enrolled. The median time to first positive CMV-TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV-CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV-CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low-level CMV reactivation, the sensitivity and negative predictive value of CMV-TCIP were 90% and 87.5%, respectively, for CD4+ CMV-TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV-TCIP. CONCLUSIONS: There was significant variability in time to CMV-CMI recovery post-HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV-CMI may protect against CS-CMVi, but immunity may be lost with GVHD diagnosis and treatment.

Influence of the substitution of different functional groups on the gas sensing and light harvesting efficiency of zero-dimensional coronene quantum dot: A first principle DFT study.

The present study accounts for the structural and electronic properties of a zero-dimensional coronene quantum dot (QD) and its substituted structures with seven different functional groups. The substitution of functional groups lead to the alteration of the centrosymmetric geometry of the coronene flake and thus, incredible properties were observed for the functionalized QDs. The increment in the band gap after the substitution of the functional groups was responsible for the increase in the chemical stability. The cohesive energy however decreased for the functional QDs. Fourier transform Infrared spectra were traced for all the QDs to confirm the availability of the functional groups and their participation in the chemical reactivity. After the substitution of functional groups, the extremely enhanced light harvesting efficiency of functionalized QDs was obtained. Furthermore, the sensing capability of the functionalized QDs for CO, CO2, and NH3 was also calculated and it was found that C-cyano, C-nitro, C-nitroso, C-pyrrolidine, and C-thionyl QDs have better sensing capabilities for CO2 molecules. C-pyrrolidine had the highest value of light harvesting efficiency of about 96%. This reflects the potential photosensitive candidature of C-pyrrolidine. Therefore, the present study sets a perfect benchmark for designing and fabricating efficient photosensitive materials and gas-sensing devices using the introduced QDs in the near future.

From the discovery of helminths to the discovery of their carcinogenic potential.

Cancer involves a major aberration in the normal behaviour of cells, making them divide continuously, which interferes with the normal physiology of the body. The link between helminths and their cancer-inducing potential has been proposed in the last century. The exact pathway is still not clear but chronic inflammation in response to the deposited eggs, immune response against soluble egg antigens, and co-infection with a third party (a bacteria, a virus, or infection leading to a change in microbiome) seems to be the reasons for cancer induction. This review looks into the historical outlook on helminths along with their epidemiology, morphology, and life cycle. It then focuses on providing correlations between helminth infection and molecular mechanism of carcinogenesis by elaborating upon epidemiological, clinical, and surgical studies. While the cancer-inducing potential has been convincingly established only for a few helminths and studies point out towards possible cancer-inducing ability of the rest of the helminths elucidated in this work, however, more insights into the immunobiology of helminths as well as infected patients are required to conclusively comment upon this ability of the latter.

Expression of angiogenic factors in the placenta of heme oxygenase-1 deficient mouse embryo.

Heme oxygenase 1 (Hmox1), the inducible form of heme degrading enzymes Hmoxs, is important for establishment and maintenance of pregnancy. A growing body of evidence suggests an association between Hmox1 and angiogenesis, including placental angiogenesis. In this study, we examined the expression of two angiogenic factors in the placentas of Hmox1 deficient mouse embryos, whose expression was found to be related to that of Hmox1. Relative protein levels and localization of Hmoxs and two angiogenic factors [Vegf and Prolactin along with their receptors, and Cd31/Pecam1] were compared in the placentas of Hmox1 wildtype and knockout mouse embryos using western blotting and immunohistochemistry along with histological analysis. The results revealed tissue disorganisation, reduced area of labyrinth and smaller nuclear size of trophoblast giant cell in the placentas of knockout embryos. The levels of Hmox2, prolactin, and Cd31/Pecam1 were found to be altered in knockout placentas, whereas Vegf and its receptors seem to be unaltered in our samples. Overall, our findings imply that Hmox2 is unlikely to compensate for Hmox1 deficiency in knockout placentas, and altered levels of prolactin and Cd31/Pecam1 hint towards impaired angiogenesis in these placentas. Further investigation would be needed to understand the molecular mechanism of defective angiogenesis in the placentas of Hmox1 knockout mouse embryos.

Schistosoma japonicum Associated Colorectal Cancer and Its Management.

BACKGROUND: An association between Schistosoma japonicum and colorectal cancer in humans has been known since a long time; however, this association remains understudied and lacks comprehensive experimentation support. OBJECTIVE: Various epidemiological and pathological studies have established the role of chronic inflammation as a major factor behind the induction of colorectal cancer. The aim of this review is to present the current knowledge on the association of Schistosoma japonicum with colorectal cancer. RESULT: Mechanisms which lead to induction and progression of colorectal cancer are highlighted along with diagnosis and treatment for the same. Further, various methodologies, including mass drug administration, use of new drugs and vaccines, role of apoptosis, and histone-modifying enzymes, have been described which can either prevent the schistosomal infection itself or can check it from reaching an advanced stage. CONCLUSIONS: Epidemiological, clinical, pathological and surgical studies suggest that Schistosoma japonicum is responsible for induction of colorectal cancer. However, thorough clinical studies are required to support and globally accept this notion. Further, methodologies highlighted in this work can be employed in order to take care of schistosomal infection or address the cancer induction and progression.

Impact of Fluoroquinolone Prophylaxis on Neutropenic Fever, Infections, and Antimicrobial Resistance in Newly Diagnosed AML Patients.

INTRODUCTION: Fluoroquinolone prophylaxis is recommended during induction chemotherapy for patients with acute myeloid leukemia (AML) to reduce risk of neutropenic fever and systemic bacterial infections. We evaluated the effectiveness of primary fluoroquinolone prophylaxis in an area with high fluoroquinolone resistance. MATERIALS AND METHODS: We performed a retrospective chart review of newly diagnosed adult AML patients who received frontline therapy at Mount Sinai Hospital in New York, NY, between 2012 and 2019. Primary outcome was development of neutropenic fever. Secondary outcomes were development of systemic bacterial infections and infections with multidrug-resistant organisms and Clostridioides difficile. Infectious outcomes were collected through 6 months after therapy initiation. We estimated the effect of fluoroquinolone prophylaxis with a time-dependent Cox proportional hazards model. RESULTS: Of 121 included patients, 87 received antibiotic prophylaxis and 34 did not. There was no difference in baseline characteristics, although the prophylaxis group had longer neutropenia duration (median 30 vs. 23 days, P = .013). The prophylaxis group had a reduced risk of neutropenic fever (hazard ratio 0.59, P = .039). The prophylaxis group had fewer gram-positive (P = .043) and gram-negative (P = .049) bloodstream infections and fewer clinically documented infections during frontline therapy (P = .005) and follow-up (P = .026). There was no difference in incidence of C. difficile or infection with fluoroquinolone-resistant or multidrug-resistant organisms. There was no mortality difference between groups. CONCLUSION: In an area with high fluoroquinolone resistance, primary fluoroquinolone prophylaxis in newly diagnosed AML patients reduced the risk of neutropenic fever and systemic bacterial infections without increased antimicrobial resistance. Prospective, randomized studies are needed to confirm these observations.

Prolactin and its significance in the placenta.

Prolactin, a pituitary hormone that was discovered about 80 years ago and is primarily known for its functions in mammary gland development and lactation, is now known to participate in numerous functions across different phylogenetic groups. Fundamentally known for its secretion from lactotroph cells in adenohypophysis region of pituitary gland, newer studies have demonstrated a number of extrapituitary sites which secrete prolactin, where it acts in an autocrine, paracrine, and endocrine manner to regulate essential physiological and biochemical processes. These sites include lymphocytes, epithelial cells of lactating mammary glands, breast cancer cells of epithelial origin, and the placenta. The placenta is one of the most important organs secreting prolactin; however, its role in placental biology has not to date been reviewed comprehensively. This review elaborates upon the various facets of prolactin hormone, including prolactin production and its post-translational modifications and signaling. Major emphasis is placed on placental prolactin and its potential roles, ranging from the role of prolactin in angiogenesis, preeclampsia, maternal diabetes, and anti-apoptosis, among others.

A comprehensive exploration of pharmacological properties, bioactivities and inhibitory potentiality of luteolin from Tridax procumbens as anticancer drug by in-silico approach.

Tridax procumbens is a flowering plant of the Asteraceae family with a wide range of medicinal uses like anti-inflammatory, anti-diabetic, anti-microbial, immunomodulatory, etc. This study aimed to investigate the anti-cancerous activity of human lung cancer for targeting luteolin, a phytochemical of Tridax procumbens. The computational study has been done for studying the structural properties of luteolin. The drug-likeness of the molecule has been predicted by virtual screening of ADMET properties. The molecular docking technique of the in-silico method is performed to check the complex formation between protein and ligand. The reactivity and stability of the molecule are investigated with the help of molecular dynamics (MD) simulations. In the present work, we have tried to establish a strong candidature of any of the phytochemical of Tridax Procumbens as an inhibitor against human lung cancer. Supplementary information: The online version contains supplementary material available at 10.1007/s11224-022-01882-7.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID-19).

The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.

Isavuconazole for the prophylaxis and treatment of invasive fungal disease: A single-center experience.

BACKGROUND: Invasive fungal disease (IFD) is a serious complication among the immunocompromised population. Isavuconazole is a newer broad-spectrum antifungal agent with promising efficacy and safety. However, there remains limited data to favor its use over current first-line agents. OBJECTIVES: We aimed to evaluate isavuconazole use and describe rates of associated breakthrough invasive fungal disease (bIFD). METHODS: A single-center, retrospective study was conducted to evaluate patients receiving isavuconazole for prophylaxis or treatment of IFD between July 1, 2017 and December 31, 2018. Patient-related and outcomes data were extracted from electronic medical records. Descriptive statistics were used to analyze our findings. RESULTS: A total of 54 patients received 61 isavuconazole courses. Isavuconazole was most commonly prescribed for primary prophylaxis in the acute myeloid leukemia (AML) and allogeneic hematopoietic stem cell transplant (HSCT) population along with treatment for possible invasive fungal disease. The primary reasons for choosing isavuconazole included QTc shortening effects, decreased risk of acute kidney injury, broader spectrum of activity, and concern for breakthrough invasive fungal disease on a different prophylactic agent. We found a breakthrough rate of 8.5% for patients and 7.8% for courses. CONCLUSIONS: Isavuconazole appears to be a promising alternative for prophylaxis and treatment of invasive fungal disease. We observed similar bIFD rates and improved tolerability when compared to historical data for posaconazole and voriconazole.

Computational study of the intermolecular interactions and their effect on the UV-visible spectra of the ternary liquid mixture of benzene, ethanol and propylene glycol.

Quantum chemical calculations are well-equipped to provide answers to the questions regarding the different aspects of intermolecular interactions. We investigate the benzene, ethanol and 1,2 propanediol ternary mixture with theoretical as well as experimental UV-Vis spectroscopy. An extensive theoretical study on the molecular structure and UV-Vis spectral analysis was undertaken using density functional theory (DFT) method. Structural parameter analysis and the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) energy gap help to describe the possible interaction between molecules in dimer and in combination. Interaction energy has been calculated from topological study. Time-dependent density functional theory (TDDFT) calculations on dimer/cluster in gas phase help to understand the effect of the molecular interaction on the overall spectral shift and related intensity variation. Our results show that in the ternary mixture, the interaction energies of the interactions are π-π interaction: 0.52-2.57 kcal/mol, Hp-π interaction: 1.15 kcal/mol and H-bonding: 2.49 to 4.46 kcal/mol. The π-π interaction and H-bonding cause red shift in absorption spectra while Hp-π interaction causes blue shift. In the ternary mixture, the strength of different kinds of interaction depends on the concentration, and as each interaction has its own effect on spectral shift, the overall experimental spectra get broader and distorted from the Gaussian shape.

Practicing Antimicrobial Stewardship: De-Escalating Antibiotics in Patients With Acute Myeloid Leukemia and Neutropenic Fever.

We compared risk of recurrent fever in patients with acute myeloid leukemia undergoing induction chemotherapy with febrile neutropenia without an infectious source in which antibacterials were de-escalated before neutrophil recovery versus continued. There was less recurrent fever when antibacterials were de-escalated early with no increased adverse events.

A lymphoma patient with Cytomegalovirus retinitis and post-autologous hematopoietic cell transplantation immune reconstitution uveitis: A case report and review of the literature.

Cytomegalovirus (CMV) retinitis in hematologic malignancies in the absence of hematopoietic cell transplant (HCT) is uncommon. We report a case of a 54-year-old woman with peripheral T-cell lymphoma who develops CMV retinitis and subsequently undergoes an autologous HCT, with eventual development of immune reconstitution uveitis. We further reviewed the PubMed literature on CMV retinitis in patients with lymphoma. We describe that CMV retinitis in patients with lymphoma has variable clinical presentations, may occur at any time during the course of the disease and chemotherapy, and is associated with significant morbidity.

Higher rates of rejection in HIV-infected kidney transplant recipients on ritonavir-boosted protease inhibitors: 3-year follow-up study.

Rejection rates in HIV-infected kidney transplant (KTx) recipients are higher than HIV-negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug-drug interactions, likely influencing outcomes. This is an IRB-approved, single-center, retrospective study of adult HIV-infected KTx patients between 5/2009 and 12/2014 with 3-year follow-up, excluding antibody-depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre-transplant dialysis. All patients received IL-2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir-boosted PI-based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1-, 2-, and 3-year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy-proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV-infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.

Primary Tubercular Granulomatous Thyroiditis, Presenting as Thyroid Nodule with Hyperthyroidism, Pyrexia of Unknown Origin and Severe Anemia.

Tuberculosis of Thyroid gland is a rare entity even in countries with high prevalence of tuberculosis. The patients present with a broad spectrum of manifestations ranging from an isolated painful nodule to frank hyperthyroidism. We report an interesting case of primary tubercular granulomatous thyroiditis, presenting as a thyroid nodule with pyrexia of unknown origin, hyperthyroidism and severe anaemia which responded to anti tubercular and anti-inflammatory treatment with complete recovery, as evidenced by blood reports and CT scan reports. Thus, proper diagnosis may avoid unnecessary surgical interventions, that were a trend in the past.

Screening recipients of increased risk donor organs: A multicenter retrospective study.

Organ Procurement & Transplantation Network policy requires post-transplant screening of recipients of organs from donors at increased risk for transmission of HIV, hepatitis B virus, and hepatitis C virus. Available data suggest that follow-up testing of recipients is not routinely conducted. Data on increased risk donors and recipients of their organs from 2008 to 2012 were retrospectively collected from 6 transplant centers after IRB approval. Descriptive statistics were performed. About 363 (60%) recipients were screened for transmission of HIV, HBV, and/or HCV at some time point; 257 (70.8%) within 90 days of transplant. The type of test used to screen for infection was variable with many recipients (25%-43%) screened with serology alone. Our results reveal that post-transplant screening for HIV, HBV, and HCV in recipients of increased risk donor organs did not universally occur and testing methods were variable.

A case of late-onset cytomegalovirus myocarditis in an orthotopic heart transplant recipient; case report and review of the literature.

We describe a male patient who presents 2 years posttransplant with cough and dyspnea. A negative pulmonary workup led to an endomyocardial biopsy and the diagnosis of cytomegalovirus (CMV) myocarditis. The patient was treated with ganciclovir and intravenous immunoglobulin. This illustrates a very late presentation of posttransplant CMV myocarditis and the usefulness of myocardial biopsy in diagnosis of CMV carditis.

Elevated Serum Beta-D-Glucan with Pseudomonas, Aspergillus, and a Partially Acid-Fast Organism in Respiratory Cultures: A Case of Hickam's Dictum Over Occam's Razor.

We describe a case of a man with ectopic Cushing's syndrome, elevated serum beta-D-glucan, and respiratory cultures with Pseudomonas, Aspergillus, and a partially acid-fast organism. Our case highlights challenges in diagnosis and management of coinfection in an immunocompromised host.