To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We ...included case‐control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random‐effect models meta‐analysis served to pool data. We identified eleven case‐control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio OR = 7.26; 95% confidence interval CI = 1.05‐50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10‐2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13‐6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67‐23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37‐12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60‐37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12‐6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78‐5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46‐0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold‐active prophylaxis to this subgroup of KT recipients at highest risk.
The authors identify several risk factors associated with the development of invasive aspergillosis in kidney transplant recipients.
Coronavirus disease 2019 (COVID‐19) can lead to a massive cytokine release. The use of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this ...hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6‐point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6‐point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon‐β (adjusted odds ratio aOR: 0.23; 95% confidence interval CI: 0.06‐0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06‐0.99; P = .048) were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C‐reactive protein levels dropped by day 2. There were no TCZ‐attributable adverse events. In this observational single‐center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID‐19 pneumonia.
Highlights
COVID‐19 can lead to a hyperinflammatory state that mirrors the cytokine release syndrome.
The off‐labeluse of the anti‐interleukin‐6 receptor monoclonal antibody tocilizumab has been proposed to abrogate this deleterious inflammatory response, although the supporting evidence is scarce.
In the present single‐centre study comprising 88 consecutive patients with COVID‐19 pneumonia that received at least one dose of intravenous tocilizumab between March 16 and 27, 2020, the rates of clinical improvement (defined by discharge to home and/or a decrease of = 2 points on a six‐point ordinal scale) were 44.3% (39/88) and 73.9% (65/88) by days 7 and 14, respectively.
The previous or concomitant use of interferon‐β and baseline serum lactate dehydrogenase levels >450 U/L were negatively associated with clinical improvement by day 7. All‐cause mortality was 6.8%, with no tocilizumab‐attributable adverse events.
Background
Which are the consequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in liver transplant (LT) recipients?
Methods
We attempted to address this question by ...reviewing our single‐center experience during the first 2 months of the pandemics at a high incidence area.
Results
Nineteen adult patients (5 females) were diagnosed by May 5, 2020. Median age was 58 (range 55‐72), and median follow‐up since transplantation was 83 (range 20‐183) months. Cough (84.2%), fever (57.9%), and dyspnea (47.4%) were the most common symptoms. Thirteen patients (68.4%) had pneumonia in x‐ray/CT scan. Hydroxychloroquine was administered in 11 patients, associated with lopinavir/ritonavir and interferon β in 2 cases each. Immunomodulatory therapy with tocilizumab was used in 2 patients. Immunosuppression (IS) was halted in one patient and modified in only other two due to potential drug interactions. Five (26.3%) patients were managed as outpatient. Two patients (10.5%) died, 10 (52.6%) were discharged home, and 2 (10.5%) were still hospitalized after a median follow‐up of 41 days from the onset of symptoms. Baseline IS regimen remained unchanged in all surviving recipients, with good liver function.
Conclusions
Our preliminary experience shows a broad spectrum of disease severity in LT patients with COVID‐19, with a favorable outcome in most of them without needing to modify baseline IS.
Bacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur ...following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0-9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with reactive arthritis were frequently treated only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons). Attributable mortality was higher for patients aged ≥65 years (7.4% vs 2.1%; p = 0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was resumed in only 2 of 36 patients with available data (5.6%), with an uneventful outcome. In the absence of an apparent predictor of the development of disseminated BCG infection after intravesical therapy, and considering the protean variety of clinical manifestations, it is essential to keep a high index of suspicion to initiate adequate therapy promptly and to evaluate carefully the risk-benefit balance of resuming intravesical BCG immunotherapy.
•Laboratory diagnosis of Strongyloides stercoralis is based in combining low-sensitive parasitological techniques and serological tests.•The most sensitive parasitological test is agar-plate culture, ...to date, the required time of incubation have not been properly studied.•An incubation time of at least 7 days is required for diagnosis of strongyloidiasis.•Incubating the plates below 2 and 5 days, could miss an important percentage of patients.
Agar-plate culture (APC) remains the most sensitive parasitological technique for S. stercoralis diagnosis. Although it was first described three decades ago, the time of incubation of the plates is neither a commonly described feature nor usually standardized. The aim of the study was to analyze the required time to detect S. stercoralis larvae in APC.
A prospective laboratory-based study including all patients with at least one positive APC was performed. The plates were incubated at room temperature for 7 days. Clinical, analytical and parasitological features including results of the direct visualization of the stool (DV) after formalin-ether concentration and time-to-detection (TTD) of the larvae in APC were recorded.
A total of 141 samples from 75 patients had a positive APC. In 49 of them (65.3%) three or more stool samples were processed for direct visualization (DV) and APC. Of these 49 patients, 8 (16.3%) were also diagnosed with DV and 41 (83.7%) were diagnosed only with APC. In 38 samples from 23 (30.7%) patients, the TTD was below 2 days, while in 27 samples from 13 (17.3%) patients, the larvae were detected on the 6th and 7th day.
Direct visualization failed to detect S. stercoralis in most of the patients that were diagnosed with APC. Incubation periods below 2 and 5 days would miss an important percentage of infections. At least 7 days of incubation of the APC are required to detect presumably low-burden chronic infections in non-endemic countries.
Background
Invasive fungal infection, particularly intraabdominal candidiasis, exerts a negative impact on the outcome of pancreas transplant recipients (PTRs). Optimal antifungal prophylaxis in this ...context remains unclear.
Methods
We performed a single‐centre retrospective study to compare the incidence of invasive candidiasis during the first 6 post‐transplant months in a cohort of 218 PTRs over two periods in which different agents for antifungal prophylaxis were used: fluconazole (Fluco‐Px) from March 1995 to June 2012, and micafungin followed by fluconazole (Mica‐Px) from July 2012 to December 2018.
Results
A total of 152 and 66 PTRs received Fluco‐Px and Mica‐Px. Mean age was 39.7 ± 7.8 years, 56.4% (123/218) were males, and 85.3% (186/218) underwent simultaneous pancreas–kidney transplantation. Invasive candidiasis occurred in 21.7% (33/152) of PTRs under Fluco‐Px compared to 24.2% (16/66) of those under Mica‐Px (p‐value = .681). Median time from transplantation to infection was 8 days (interquartile range IQR: 6–16) under Fluco‐Px versus 6.5 (IQR: 3.3–15.8) under Mica‐Px (p‐value = .623). Non‐albicans Candida species comprised 27.5% (11/40) and 25.0% (4/16) of episodes under Fluco‐Px and Mica‐Px respectively (p‐value = .849). Surgical site infection was the most common form in both groups (82.5% 33/40 and 87.5% 14/16; p‐value = .954). Multivariable analysis identified cold ischaemia time of the pancreas and kidney grafts, surgical reintervention and insulin requirement after transplantation as risks factor for invasive candidiasis.
Conclusion
This retrospective study did not reveal a significant benefit from the initial use of micafungin‐based antifungal prophylaxis over fluconazole among PTRs in terms of invasive candidiasis.
Strongyloidiasis affects an estimated 600 million people worldwide, especially in tropical and subtropical areas. Single-dose ivermectin treatment has shown to be effective among immunocompetent ...patients with uncomplicated strongyloidiasis. Here, we present the protocol of the ImmunoStrong study, a prospective observational study aiming to evaluate the effectiveness and safety of a single-dose ivermectin for treatment of uncomplicated strongyloidiasis in immunosuppressed patients. The secondary objectives are to assess accuracy of molecular techniques for the follow-up of these patients and to determine the population pharmacokinetics of ivermectin. The information retrieved by this study will cover relevant information gaps in the strongyloidiasis management among immunosuppressed patients.
Previous studies have suggested an increased susceptibility of COVID-19 among certain populations. We analyzed whether COVID-19 presentation and mortality differ between Latinx migrants and Spanish ...natives. Methods and Materials. COVID-19 patients between 35-64 years old admitted between January 26th-May-5th 2020 were reviewed. Demographics, major comorbidities, symptoms, signs and analytical parameters on admission were recorded. Respiratory failure was defined as PaO2/FiO2 ≤ 200 mmHg, noninvasive or invasive mechanical ventilation requirement at any time during hospitalization. A propensity score (PS) adjustment was created between Latinx and Spanish. A multivariable logistic regression model adjusted by the PS was performed to evaluate the effects of different variables on mortality. Results. 894 patients: 425 (47.5%) Latinx and 469 (52.5%) Spanish natives were included. Latinx were younger (50 vs 55 years p < 0.001) and had less comorbidities (29.4% vs 55.0% p < 0.001) than Spanish natives. More often they exhibited fever (22.1% vs 9.8% p = 0.018) and had higher inflammatory markers (PCR) (11.3 mg/dl vs 7.7 mg/dl p < 0.001). Mortality seemed lower among Latinx (4.7% vs 8.7%, p = 0.017). No association was found between ethnicity and mortality. Respiratory failure OR = 23.978 (CI 95% 9.4-60.1) p < 0.001, LDH OR (per unitary increment) = 1.002; CI95% (1.000-1.004;p = 0.036 and PCR OR (per unitary increment) = 1.044 (CI95% 1.06-1.08); p = 0.02 were independently associated to mortality. Conclusions: We were unable to identify significant ethnic disparities between Latinx and Spanish natives in terms of COVID-19 mortality. Universal access to the health care system in Spain may have contributed to a better outcome of Latinx patients. Differences previously described might be a consequence of socioeconomic disparities.
•An increasing number of immunomodulatory therapies are being tested for COVID-19.•A survival benefit has been shown with the use of corticosteroids.•The role of combination therapy with ...corticosteroids and tocilizumab is unclear.•This study analyzed a single-center cohort of patients aged ≥65 years with severe COVID-19.•The sequential use of corticosteroids and tocilizumab was associated with better outcomes.
The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear.
A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400–600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied.
Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio HR: 0.34; 95% confidence interval CI: 0.17–0.68; P=0.002) and IPTW-weighted models (odds ratio OR: 0.38; 95% CI: 0.21–0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21–0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49–3.41; P<0.001). The occurrence of secondary infection was similar between both groups.
The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.
•Immunomodulatory treatment could improve the prognosis of COVID-19.•Patients who received anakinra as rescue therapy were compared with controls.•Anakinra did not improve in-hospital prognosis of ...patients after tocilizumab failure.
A subgroup of patients with SARS-CoV-2 infection was thought to have developed cytokine release syndrome and were treated with tocilizumab; however, a significant percentage of patients evolved. This study aimed to determine the usefulness of anakinra as a rescue treatment for patients with tocilizumab-refractory COVID-19 disease.
A prospective cohort of patients with COVID-19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) with selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline, and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a 6-point ordinal scale, from baseline to day 21.
The study included 20 cases and 20 controls (mean age 65.3 ± 12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. The in-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P = 0.527).
Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19.
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