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.

Full Dynamical and Ab Initio Investigation of the Electron Transfer-Mediated Decay Mechanism of He+ in the Presence of Heavier Alkali Dimers.

We have studied the electron transfer-mediated decay (ETMD) process for the 1s ionized state of the He atom in the presence of a heavier alkali homonuclear dimer (Na2, K2, and Rb2) as well as heteronuclear dimer (LiNa, NaK, and KRb). In our computation, we have considered all the alkali dimers being in the singlet electronic ground state. The electron transfer from the alkali dimer to He (1s-1) leads to the emission of another electron from the alkali dimer into the continuum. We have investigated the impact of the distance of the He atom from the center of mass of the alkali dimer on the ETMD decay width. We also performed the Born-Oppenheimer molecular dynamics simulation to understand the impact of nuclear dynamics on the ETMD process.

Clinical course and molecular characterization of human Bocavirus associated with acute lower respiratory tract infections in tertiary care hospital of north India.

Respiratory samples from 139 hospitalized children were screened for the Human Bocavirus (HBoV) genome. Positive samples were sequenced for partial VP1/VP2 gene followed by molecular and phylogenetic analyses. HBoV positivity was noted in 7.2% (10/139) patients. All HBoV positive children presented with fever followed by cough and respiratory distress (90%; 9/10). Three children developed multisystemic viral illness with one fatality. Eight children required intensive care management and mechanical ventilation required for 5 children. Nucleotide percent identity of partial VP1/VP2 gene of HBoV study strains were ranging from 97.52% to 99.67%. Non-synonymous amino acid mutations in VP1 protein revealed T591S (n=8) and Y517S (n=1) mutations in comparison to HBoVSt1 strain where N475S (n=8) and S591T (n=2) mutations in comparison to HBoVSt2 strain. One study strain showed A556P, H556P, I561S and M562R non-synonymous mutations. All the study strains belong to HBoV1 type. Seven HBoV strains belong to same lineage and three belong to another lineage. For evolutionary dynamics, GTR+I substitution model with uncorrelated relaxed lognormal clock and Bayesian Skyline tree prior showed 9.0 x 10-4 [95% HPD interval: 3.1 x10-6, 2.1 x 10-3] nucleotide substitutions/site/year. The clinical suspicion and virological screening is necessary for identification HBoV in children.

Comprehensive quantum chemical study of the associative complex of para-aminobenzoic acid and 7-diethylamino 4-methyl coumarin by adsorption and aromatic bridges.

CONTEXT: The present study accounts for the quantum chemical and nonlinear optical properties of the combination of para-aminobenzoic acid and 7-diethylamino 4-methyl coumarin. Three different complexes were designed, surface interaction (adsorption) and two by connecting both molecules with π-bridge benzene and biphenyl. The amino and carboxyl groups were observed to behave as strong donor and acceptor sites in all the complexes. The band gap of the adsorbed complex was found more suitable. The absorption wavelength and intensity both were seen to increase with the increase in the number of benzene rings in the π-bridge. The values of first- and second-order hyperpolarizability suggest the improved nonlinear optical responses of the introduced complexes. Additionally, the negative value of second-order hyperpolarizability suggests the possibility of the occurrence of reverse saturable absorption in these combinations. The reported work gives theoretical insights into the nonlinear optical properties of the combination of para-aminobenzoic acid and 7-diethylamino 4-methyl coumarin. METHODS: The molecular modeling and the quantum chemical studies were performed with Gaussian software packages. The standard B3LYP-6-311++G(d,p) basis functionals were used for energy minimization and other spectral calculations. All the surface analyses reported here are obtained by employing Multiwfn software. The chemical reactivity was established by the global reactivity descriptors. The intramolecular interactions and charge localization were stated using inter-fragment charge transfer analysis.

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.

18F-FDG PET/CT in left ventricular assist device infections: In-depth characterization and clinical implications.

BACKGROUND: Previous retrospective studies suggest a good diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) in left ventricular assist device (LVAD) infections. Our aim was to prospectively evaluate the role of PET/CT in the characterization and impact on clinical management of LVAD infections. METHODS: A total of 40 patients (aged 58 [53-62] years) with suspected LVAD infection and 5 controls (aged 69 [64-71] years) underwent 18F-FDG-PET/CT. Four LVAD components were evaluated: exit site and subcutaneous driveline (peripheral), pump pocket, and outflow graft. The location with maximal uptake was considered the presumed site of infection. Infection was confirmed by positive culture (exit site or blood) and/or surgical findings. RESULTS: Visual uptake was present in 40 patients (100%) in the infection group vs 4 (80%) control subjects. For each individual component, the presence of uptake was more frequent in the infection than in the control group. The location of maximal uptake was most frequently the pump pocket (48%) in the infection group and the peripheral components (75%) in the control group. Maximum standard uptake values (SUVmax) were higher in the infection than in the control group: SUVmax (average all components): 6.9 (5.1-8.5) vs 3.8 (3.7-4.3), p = 0.002; SUVmax (location of maximal uptake): 10.6 ± 4.0 vs 5.4 ± 1.9, p = 0.01. Pump pocket infections were more frequent in patients with bacteremia than without bacteremia (79% vs 31%, p = 0.011). Pseudomonas (32%) and methicillin-susceptible Staphylococcus aureus (29%) were the most frequent pathogens and were associated with pump pocket infections, while Staphylococcus epidermis (11%) was associated with peripheral infections. PET/CT affected the clinical management of 83% of patients with infection, resulting in surgical debridement (8%), pump exchange (13%), and upgrade in the transplant listing status (10%), leading to 8% of urgent transplants. CONCLUSIONS: 18F-FDG-PET/CT enables the diagnosis and characterization of the extent of LVAD infections, which can significantly affect the clinical management of these patients.

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

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.

Altered Expression of Heme Oxygenase 2 in Heme Oxygenase 1-deficient Mouse Embryos.

Heme oxygenases (Hmoxs) are enzymes that catalyze the first and rate-limiting step in the degradation of heme to carbon monoxide, iron, and biliverdin. The two main isozymes, namely Hmox1 and Hmox2, are encoded by two different genes. Mutation of the Hmox1 gene in mice is known to cause extensive prenatal lethality, and limited information is available about the expression of Hmox proteins in developing mouse embryos. In this study, immunohistochemistry was used to perform a detailed investigation comparing Hmox proteins in Hmox1 wild-type and knockout (KO) mouse embryos collected from wild-type and heterozygous timed-matings. Western analysis for Hmoxs was also done in the organs of late-gestation embryos. The results demonstrated cytoplasmic and nuclear localization of Hmoxs in all the organs examined in wild-type embryos. Interestingly, Hmox2 immunoreactive protein signals were significantly low in most of the organs of mid- and late-gestation Hmox1-KO embryos. Furthermore, relative levels of Hmox2 were revealed to be significantly lower in the lung and kidney of late-gestation Hmox1-KO embryos by western analysis, which complemented the immunohistochemistry findings in these two organs. The current study provides detailed immunoexpression patterns of Hmox proteins in wild-type and Hmox1-KO mouse embryos in mid- and late-gestation.

Paradigm shift of respiratory viruses causing lower respiratory tract infection in children during COVID-19 pandemic in India.

INTRODUCTION: Acute lower respiratory tract infections (ALRTIs) are the commonest cause of mortality in children mostly attributed to respiratory viruses. During the coronavirus disease 2019 (COVID-19) pandemic, the dynamics and transmission of infections changed worldwide due to widespread public health measures. This study aimed to understand the pattern of respiratory viruses associated with ALRTIs in children pre and during COVID-19 pandemic in India. METHODOLOGY: Respiratory samples were collected from ALRTI patients during pre-pandemic period (October 2019 to February 2020; n = 166), Delta (July 2021 to December 2021; n = 78) and Omicron wave (January 2022 to July 2022; n = 111). Samples were screened for Influenza (Inf) A pdmH1N1, InfA H3N2, InfB, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human bocavirus (hBoV), human rhinovirus (hRV), and parainfluenza virus (PIV-2 and PIV-3) by nucleic acid amplification techniques (NAATs). RESULTS: Significantly higher proportion of children with ALRTIs had virus/es isolated during pre-pandemic period than during mid-pandemic period [78.9% (131/166) vs. 52.9% (100/189); p < 0.001). RSV positivity was significantly higher (51.2%) in pre-pandemic period than 10.3% and 0.9% during the Delta and Omicron waves respectively. No significant difference in positivity rate of Inf A pdmH1N1, Inf A H3N2 and Inf B was seen. The increase in positivity of hRV (39.2% vs 42.3% vs 56.8%) and hBOV (1.2% vs 5.1% vs 9%) was documented in pre-pandemic, delta wave and omicron wave respectively. CONCLUSIONS: The COVID-19 pandemic significantly impacted the frequency and pattern of respiratory viruses among hospitalized children with ALRTIs in India.

HIV-Positive Liver Transplant Does not Alter the Latent Viral Reservoir in Recipients With Antiretroviral Therapy-Suppressed HIV.

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10). All measures remained stable from baseline by 1 year posttransplant. These data demonstrate that the LVR is stable after liver transplantation in people with HIV. Clinical Trials Registration. NCT02602262 and NCT03734393.

Efficacy of ceftazidime-avibactam in solid organ transplant recipients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae.

We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P = .011) and 30-day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P = .053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.03-6.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.

Study of nonlinear optical responses of phytochemicals of Clitoria ternatea by quantum mechanical approach and investigation of their anti-Alzheimer activity with in silico approach.

Clitoria ternatea is a flowering plant with promising medicinal plants with a wide variety of active phytochemicals. The present study aimed at the computational investigation of the nonlinear optical (NLO) responses of the active phytochemicals of the Clitoria ternatea. The computational investigation of the NLO features was done by using the density functional theory (DFT) by B3LYP/6-311G + + (d, p) basis set. The structural parameters, mulliken charge distribution, and molecular electrostatic potential (MEP) surface clearly show the intramolecular charge transfer within Clitorin. The NLO properties were identified by computing the polarizability parameters. As the plant has high medicinal characteristics, the inhibiting properties of its phytochemicals were also investigated to combat Alzheimer disease (AD). The systematic in silico study identifies Clitorin as the most active and inhibiting phytochemicals of the plant. The results obtained from molecular dynamics (MD) simulation tell the stability of the complex and make it a fair selection as a drug-like molecule against AD. The cardio-toxicity analysis done for the Clitorin molecule verifies that it is harmless for the heart. Supplementary information: The online version contains supplementary material available at 10.1007/s11224-022-01981-5.

Determination and analysis of sex ratios in heme oxygenase 1 gene targeted mouse embryos.

Heme oxygenase 1 or Hmox1 enzyme is involved in catalyzing the first and rate-limiting step in heme breakdown reactions. Many studies have reported a partial lethality of Hmox1 knockout mice obtained from heterozygous breeding pairs. Similar results were obtained in our transgenic mice colony and a sex specific bias was observed in the favor of males in the adult mice. Hmox1 independent factors which could have caused this bias were initially analyzed and it was found that those factors were not a reason behind this anomaly. Certain studies involving gene knockout hinted toward a prenatal or neonatal lethality of female knockout mice embryos or pups, respectively. In order to check if this bias was occurring in embryonic stages, that is, either if mutant female embryos were dying or if heterozygous mothers were not carrying embryos to term, we analyzed the sex-ratios in mid- and late-gestational ages (9.5-13.5 dpc and 14.5-18.5 dpc, respectively). Our results did not indicate any significant difference in the sex ratios in embryonic stages; hence, it was concluded that females are not dying in embryonic stages. It can be speculated that these deaths were probably occurring at neonatal age. More studies are required to confirm that the lack of Hmox1 gene products is the sole reason for this female lethality.

The effect of induction immunosuppression for kidney transplant on the latent HIV reservoir.

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRß repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRß clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.

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.

Blood Transcriptomes of SARS-CoV-2-Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity.

BACKGROUND: Among patients with COVID-19, kidney transplant recipients (KTRs) have poor outcomes compared with non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort. METHODS: We ascertained clinical data by chart review. A single sample of blood was collected for transcriptome analysis. Total RNA was poly-A selected and RNA was sequenced to evaluate transcriptome changes. We also measured cytokines and chemokines of serum samples collected during acute infection. RESULTS: A total of 64 patients with COVID-19 in KTRs were enrolled, including 31 with acute COVID-19 (<4 weeks from diagnosis) and 33 with post-acute COVID-19 (>4 weeks postdiagnosis). In the blood transcriptome of acute cases, we identified genes in positive or negative association with COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways but downregulation of T cell and adaptive immune activation pathways. This finding was independent of lymphocyte count, despite reduced immunosuppressant use in most KTRs. Compared with acute cases, post-acute cases showed "normalization" of these enriched pathways after 4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of immunosuppression. Analysis of the non-KTR cohort with COVID-19 showed significant overlap with KTRs in these functions. Serum inflammatory cytokines followed an opposite trend (i.e., increased with disease severity), indicating that blood lymphocytes are not the primary source. CONCLUSIONS: The blood transcriptome of KTRs affected by COVID-19 shows decreases in T cell and adaptive immune activation pathways during acute disease that, despite reduced immunosuppressant use, associate with severity. These pathways show recovery after acute illness.