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A prominent clinical symptom of 2019-novel coronavirus (nCoV) infection is hyposmia/anosmia (decrease or loss of sense of smell), along with general symptoms such as fatigue, shortness of breath, fever and cough. The identity of the cell lineages that underpin the infection-associated loss of olfaction could be critical for the clinical management of 2019-nCoV-infected individuals. Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2 , TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. We studied if anosmia in 2019-nCoV-infected individuals can be explained by the expression patterns associated with these host-specific moieties across the known olfactory epithelial cell types, identified from a recently published single-cell expression study. Our findings underscore selective expression of these viral entry-associated genes in a subset of sustentacular cells (SUSs), Bowman's gland cells (BGCs) and stem cells of the olfactory epithelium. Co-expression analysis of ACE2 and TMPRSS2 and protein–protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium. Furthermore, expression, structural and docking analyses of ACE2 revealed the potential risk of olfactory dysfunction in four additional mammalian species, revealing an evolutionarily conserved infection susceptibility. In summary, our findings provide a plausible cellular basis for the loss of smell in 2019-nCoV-infected patients. [ABSTRACT FROM AUTHOR]

Background. Renal papillary necrosis (RPN) is associated with a number of comorbid conditions. However, it has been rarely reported in patients with fungal infections of the kidney. Methods. We analyzed medical records of our hospital for the last two decades and identified 29 patients with fungal infections and RPN. Results. Among the 29 patients, there were 24 men and 5 women. The median (range) age at presentation was 31.2 years (2 days-73 years). Three patients (10%) were kidney transplant recipients. The remaining had varied co-existing medical conditions that included diabetes mellitus in 16 (55%) and septicemia in 4 (14%). Clinical features at presentation were fever and oliguric kidney failure in 17 patients and loin pain accompanied by passage of fleshy material per urethra in 11 (38%). Diagnosis was made ante-mortem in 17 (59%) patients. Twenty patients (69%) had infection limited to the kidneys, while in the rest, it was disseminated. Kidney involvement was bilateral in 17 patients (59%). Urinalysis showed pyuria in 23 (79%) and microhematuria in 8 (28%) patients. Fungal infections included candidiasis (69%), aspergillosis (21%) and zygomycosis (10%). Of the 17 patients in whom the diagnoses was made ante-mortem, 12 survived and 5 died. Overall mortality was observed in 48% of cases. Conclusions. We herein report a series of patients with RPN associated with fungal infections of the kidney. Presentation varies from asymptomatic urinary tract infection to severe kidney failure with poor outcome. High index of suspicion is necessary to reduce the associated high mortality in these patients. [ABSTRACT FROM AUTHOR]

Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients. [ABSTRACT FROM AUTHOR]

Odorant receptors (ORs) obey mutual exclusivity and monoallelic mode of expression. Efforts are ongoing to decipher the molecular mechanism that drives the 'one-neuron-one-receptor' rule of olfaction. Recently, single-cell profiling of olfactory sensory neurons (OSNs) revealed the expression of multiple ORs in the immature neurons, suggesting that the OR gene choice mechanism is much more complex than previously described by the silence-all-and-activate-one model. These results also led to the genesis of two possible mechanistic models i.e. winner-takes-all and stochastic selection. We developed Reverse Cell Tracking (RCT), a novel computational framework that facilitates OR-guided cellular backtracking by leveraging Uniform Manifold Approximation and Projection embeddings from RNA Velocity Workflow. RCT-based trajectory backtracking, coupled with statistical analysis, revealed the OR gene choice bias for the transcriptionally advanced (highest expressed) OR during neuronal differentiation. Interestingly, the observed selection bias was uniform for all ORs across different spatial zones or their relative expression within the olfactory organ. We validated these findings on independent datasets and further confirmed that the OR gene selection may be regulated by Upf3b. Lastly, our RNA dynamics-based tracking of the differentiation cascade revealed a transition cell state that harbors mixed molecular identities of immature and mature OSNs, and their relative abundance is regulated by Upf3b. [ABSTRACT FROM AUTHOR]

Dramatic genomic alterations, either inducible or in a pathological state, dismantle the core regulatory networks, leading to the activation of normally silent genes. Despite possessing immense therapeutic potential, accurate detection of these transcripts is an ever-challenging task, as it requires prior knowledge of the physiological gene expression levels. Here, we introduce EcTracker, an R-/Shiny-based single-cell data analysis web server that bestows a plethora of functionalities that collectively enable the quantitative and qualitative assessments of bona fide cell types or tissue-specific transcripts and, conversely, the ectopically expressed genes in the single-cell ribonucleic acid sequencing datasets. Moreover, it also allows regulon analysis to identify the key transcriptional factors regulating the user-selected gene signatures. To demonstrate the EcTracker functionality, we reanalyzed the CRISPR interference (CRISPRi) dataset of the human embryonic stem cells differentiated into endoderm lineage and identified the prominent enrichment of a specific gene signature in the SMAD2 knockout cells whose identity was ambiguous in the original study. The key distinguishing features of EcTracker lie within its processing speed, availability of multiple add-on modules, interactive graphical user interface and comprehensiveness. In summary, EcTracker provides an easy-to-perform, integrative and end-to-end single-cell data analysis platform that allows decoding of cellular identities, identification of ectopically expressed genes and their regulatory networks, and therefore, collectively imparts a novel dimension for analyzing single-cell datasets. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the leading cause of morbidity and mortality in children with chronic kidney disease (CKD). We aim to estimate the prevalence of cardiac abnormalities in children up to age 16 years with CKD and their association with various risk factors.Methods: This cross-sectional observational study was conducted on 107 CKD children. We assessed the systolic and diastolic function using 2D echocardiographic evaluation and M-mode measurements of the left ventricle (LV) indexed for BSA and z-scores were calculated. Results were compared with age, sex, stage of CKD, anaemia, estimated glomerular filtration rate (eGFR) and various laboratory parameters.Results: LV diastolic dysfunction was seen in 88%, followed by increased LV dimensions in 33.6%, LV systolic dysfunction in 16%, right ventricle systolic dysfunction in 11.2% while increased pulmonary artery (PA) systolic pressure was seen in 9.3% of cases. LV dimensions correlated directly with parathormone levels and inversely with eGFR, serum calcium and haemoglobin levels. Left ventricular hypertrophy correlated directly with parathormone while inversely with eGFR, serum calcium and haemoglobin. Ejection fraction directly correlated to eGFR and serum calcium while inversely related to parathormone. Left PA pressure directly correlated with age and inversely with eGFR. Right ventricular systolic function assessed by tricuspid annular plane systolic excursion correlated inversely with haemoglobin.Conclusion: LV diastolic dysfunction and increased LV dimensions were the most common cardiac abnormality in children with CKD. LV dimensions correlated directly with parathormone levels and inversely with eGFR, serum calcium and haemoglobin. Diastolic dysfunction positively correlated with serum creatinine and parathormone levels. [ABSTRACT FROM AUTHOR]

Background Complement 3 glomerulopathy (C3G) results from dysfunction of the alternative complement pathway (ACP). No data are available on post-transplant C3G in South Asia. Methods In this study, renal allograft biopsies of C3G patients performed from 2012 to 2017 were analysed for ACP functional assay (APFA), serum complement levels, complement factor H (CFH), complement factor B (CFB) and autoantibodies to CFH and CFB. Limited genetic screening for CFH / CFHR5 genes was carried out. All study patients were also followed up. Results A total of 21 cases of C3G were included, of which 11 had native C3G disease (that is, recurrent C3G). Of these 11 recurrent cases, 7 presented with allograft dysfunction and 4 with proteinuria and renal dysfunction. Early post-transplant recurrence (<1 month) was noted in six patients, whereas recurrence in five patients occurred within 8–17 months of transplant. Biopsies showed mild focal mesangial expansion with or without endocapillary proliferation and thrombotic microangiopathy. Rejection was also noted in six patients. APFA/C3 levels were low in all cases. Serum CFH levels were low [dense deposit disease (DDD), 44%; C3 glomerulonephritis (C3GN), 25%], whereas CFB levels were normal. Autoantibodies to CFH, CFB and C3 nephritic factor were present in 11, 0 and 44% of DDD cases, respectively, and in 17, 17 and 33% of C3GN cases, respectively. Genetic analysis revealed only non-pathogenic CFH gene variants (93%). No novel mutation was found. At follow-up (140 months), stable graft was noted in 28% of cases, progressive renal failure in 19%, graft loss in 34%, and 19% of patients died. Conclusion Post-transplant C3G can present with graft dysfunction and/or proteinuria. Subtle histological findings demand careful interpretation of immunofluorescence results. Autoantibodies to complement pathway regulatory proteins are common, and no novel mutation has been found from limited genetic workup. Clinical outcome is poor. [ABSTRACT FROM AUTHOR]

Background C3 glomerulopathy (C3G) is a heterogeneous disease caused by alternative complement pathway abnormalities without any standardized treatment. An immunosuppressive agent, mycophenolate mofetil (MMF), has been recently shown to be useful in treating C3G, mainly in studies from the west. We report the clinical outcome of 17 Indian C3G patients treated with MMF with or without steroids. Methods The clinical and histology details of the C3G patients treated with MMF for at least 6 months with a follow-up of at least 12 months were retrieved from the medical records of our center. Results The median serum creatinine and proteinuria at presentation were 0.8 mg/dL and 3.7 g/day, respectively, with the majority (88.2%) presenting as nephrotic syndrome. The mean dose of MMF was 1.65 (±0.56) g/day, and the median duration of MMF therapy was 18 months. Two-thirds (64%) of the patients responded to the treatment, with complete remission in 4 (23%) and partial remission in 7 (41%) (median time: 9 months). Three patients progressed to end-stage renal disease (ESRD) on follow-up. Of the three patients, one (33%) had an initial response in proteinuria to MMF but did not respond after a relapse and subsequently progressed to ESRD and two (67%) other patients were nonresponsive to MMF from the start of the therapy. Conclusion Despite a small sample size and lack of a control arm, this study describes the effectiveness of MMF in treating C3G patients from Asia and forms a basis for future randomized trials. [ABSTRACT FROM AUTHOR]

Summary Machine Learning-based techniques are emerging as state-of-the-art methods in chemoinformatics to selectively, effectively and speedily identify biologically relevant molecules from large databases. So far, a multitude of such techniques have been proposed, but unfortunately due to their sparse availability, and the dependency on high-end computational literacy, their wider adaptation faces challenges, at least in the context of G-Protein Coupled Receptors (GPCRs)-associated chemosensory research. Here, we report Machine-OlF-Action (MOA), a user-friendly, open-source computational framework, that utilizes user-supplied SMILES (simplified molecular input line entry system) of the chemicals, along with their activation status, to synthesize classification models. MOA integrates a number of popular chemical databases collectively harboring approximately 103 million chemical moieties. MOA also facilitates customized screening of user-supplied chemical datasets. A key feature of MOA is its ability to embed molecules based on the similarity of their local neighborhood, by utilizing a state-of-the-art model interpretability framework LIME. We demonstrate the utility of MOA in identifying previously unreported agonists for human and mouse olfactory receptors OR1A1 and MOR174-9 by leveraging the chemical features of their known agonists and non-agonists. In summary, here we develop an ML-powered software playground for performing supervisory learning tasks involving chemical compounds. Availability and implementation MOA is available for Windows, Mac and Linux operating systems. It's accessible at (https://ahuja-lab.in/). Source code, user manual, step-by-step guide and support is available at GitHub (https://github.com/the-ahuja-lab/Machine-Olf-Action). For results, reproducibility and hyperparameters, refer to Supplementary Notes. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Introduction Nearly 220000 patients are diagnosed with end-stage renal disease (ESRD) every year, which calls for an additional demand of 34 million dialysis sessions in India. The government of India has announced a National Dialysis Programme to provide for free dialysis in public hospitals. In this article we estimate the overall cost of performing hemodialysis (HD) in a tertiary care hospital. Second, we assess the catastrophic impact of out-of-pocket expenditures (OOPEs) for HD on households and its determinants. Methods The economic health system cost of HD was estimated using bottom-up costing methods. All resources, capital and recurrent, utilized for service delivery from April 2015 to March 2016 were identified, measured and valued. Capital costs were annualized after accounting for their useful life and discounting at 3% for future years. Sensitivity analyses were undertaken to determine the effect of variation in the input prices and other assumptions on the annual health system cost. OOPEs were assessed by interviewing 108 patients undergoing HD in the study hospital to account for costs from the patient's perspective. The prevalence of catastrophic health expenditures (CHEs) was computed per threshold of 40% of non-food expenditures. Results The overall average cost incurred by the health system per HD session was INR 4148 (US$64). Adjusting for capacity utilization, the health system incurred INR 3025 (US$47) per HD at 100% bed occupancy. The mean OOPE per patient per session was INR 2838 (US$44; 95% confidence interval US$34–55). The major components of this OOPE were medicines and consumables (64.1%). The prevalence of a CHE per HD session was 11.1%. Conclusion Our study findings would be useful in the context of planning for dialysis services, setting provider payment rates for dialysis under various publicly sponsored health insurance schemes and undertaking future cost-effectiveness analysis to guide resource allocation decisions. [ABSTRACT FROM AUTHOR]

Background. Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. Methods. A total of 114 adult PMN patients were studied. Anti-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by Taq- Man assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. Results. Of 114 patients, 66.7% showed elevated serum anti- PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing >90% reduction in the anti- PLA2R titer achieved remission of the nephrotic state, whereas of those showing <50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA2R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti-PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA2R levels. Conclusion. To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy. [ABSTRACT FROM AUTHOR]

Introduction Management of adults with steroid-resistant (SR) nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is a challenging task. Is tacrolimus (TAC) effective in this situation without serious adverse effects? This prospective study was done to answer this question. Materials and methods In patients with SR nephrotic syndrome due to FSGS, oral TAC (0.1 mg/kg/day) was started targeting a trough level of 5–10 ng/mL along with oral prednisolone (0.15 mg/kg/day) for 48 weeks. In patients with complete remission (CR), TAC dose was reduced to a target of 3–6 ng/mL whereas in partial responders, TAC trough levels were kept at 5–10 ng/mL. TAC was discontinued in those with no remission at 24 weeks and was deemed TAC resistant. Outcome, namely CR and partial remission (PR), was assessed at the end of 24 and 48 weeks. All patients were prospectively followed for 60 weeks. Relapses after CR or PR were recorded; adverse effects, namely nephrotoxicity (>25% rise in creatinine), cosmetic effects, infections and hyperglycemia, were recorded every month. Results A total of 44 SR-FSGS [not otherwise specified 33 (75%), tip lesion 03 (6.8%) and cellular variant 8 (18.1%)] were analyzed. Mean age was 25.16 ± 8.26 (18–51) years. Of 44 patients, CR and PR were achieved in 17 (38.6%) and 06 (13.6%) patients, respectively. TAC resistance was seen in 21 (47.7%) patients. Time taken to achieve remission was 15.2 ± 6 weeks. Five (21.7%) patients with CR had relapse on tapering the dose and seven (30.4%) after stopping TAC. Reversible nephrotoxicity was seen in seven (15.9%) and irreversible in four patients (9%). TAC-related diarrhea was the problem in 10 (22.7%), and infections were seen in 19 patients (43.1%). Impaired fasting glucose and diabetes mellitus were seen in 10 patients (22.7%). Conclusion TAC is an effective agent in the management of SR-FSGS. However, strict renal function and blood sugar monitoring is required due to its potential nephrotoxicity and diabetogenic potential. [ABSTRACT FROM AUTHOR]

Background. Cryptococcosis occurring ⩽30 days after transplantation is an unusual event, and its characteristics are not known. Methods. Patients included 175 solid-organ transplant (SOT) recipients with cryptococcosis in a multicenter cohort. Very early-onset and late-onset cryptococcosis were defined as disease occurring ⩽30 days or >30 days after transplantation, respectively. Results. Very early-onset disease developed in 9 (5%) of the 175 patients at a mean of 5.7 days after transplantation. Overall, 55.6% (5 of 9) of the patients with very early-onset disease versus 25.9% (43 of 166) of the patients with late-onset disease were liver transplant recipients (P = .05). Very early cases were more likely to present with disease at unusual locations, including transplanted allograft and surgical fossa/site infections (55.6% vs 7.2%; P < .001). Two very early cases with onset on day 1 after transplantation (in a liver transplant recipient with Cryptococcus isolated from the lung and a heart transplant recipient with fungemia) likely were the result of undetected pretransplant disease. An additional 5 cases involving the allograft or surgical sites were likely the result of donor-acquired infection. Conclusions. A subset of SOT recipients with cryptococcosis present very early after transplantation with disease that appears to occur preferentially in liver transplant recipients and involves unusual sites, such as the transplanted organ or the surgical site. These patients may have unrecognized pretransplant or donor-derived cryptococcosis. [ABSTRACT FROM AUTHOR]

Background. Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known. Methods. We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis. Results. Of 75 patients treated with polyenes as induction regimens, 55 (73.3%) received lipid formulations of amphotericin B and 20 (26.7%) received AmBd. Similar proportions of patients in both groups had renal failure at baseline (P = .94). Overall, mortality at 90 days was 10.9% in the group that received lipid formulations of amphotericin B and 40.0% in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (P = .034), renal failure at baseline (P = .016), and fungemia (P = .003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P = .007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P = .349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.02-20.80; P = .047) and fungemia (OR, 10.66; 95% CI, 2.08-54.55; P = .004) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95% CI, 0.02-0.57; P = .008). Conclusions. Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients. [ABSTRACT FROM AUTHOR]

Background. Clinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined. Methods. In a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days. Results. Renal failure (odds ratio [OR], 3.17; P = .010), diabetes mellitus (OR, 8.11; P < .001), and prior voriconazole and/or caspofungin use (OR, 4.41; P = .033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P = .002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P = .021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P ! .001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P = .023) and disseminated disease (OR, 14.6; P = .027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P = .003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables. Conclusions. The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis. [ABSTRACT FROM AUTHOR]

Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P = .048). The overall P = .048 mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P = .023), renal failure at baseline (P = .028), fungemia (P = .006 ), and disseminated infection (P = .035 ) and was lower in those receiving a calcineurin-inhibitor agent (P = .003 ). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent (P = .003) was independently associated with a lower mortality (adjusted HR, 0.21; P = .008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P = .037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients. [ABSTRACT FROM AUTHOR]

Background. We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. Methods. The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. Results. In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, my- cophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Thi proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. Conclusions. This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases. [ABSTRACT FROM AUTHOR]