Long-term outcomes, residual symptoms and quality of life in COVID-19 hospitalized patients: A 12-month longitudinal study.

The long-term impact of the coronavirus disease 2019 (COVID-19) pandemic is a critical public health concern. The presence of residual symptoms in COVID-19 survivors has been investigated with various results; however, there is limited data documenting outcomes longer than 6 months post-hospitalization. We aimed to investigate the 12-month lasting effects of COVID-19 in hospitalized patients. From October 2020 through March 2021, 92 patients were enrolled. At admission and 1, 3, 6, and 12 months post-hospitalization, demographic, clinical, laboratory and imaging data, and echocardiography and spirometry test results were recorded. Possible cognitive and functional impairment, as well as the quality of life (QoL), were also assessed. In our cohort (median age: 61 years), 31.5% had severe disease at admission, which correlated with worse laboratory findings and a longer hospital stay (p < 0.001). Inflammatory markers were associated with severity initially, but reverted to normal after 3 months. In total, 55%, 37%, 19%, and 15.5% of patients reported at least one persistent symptom in months 1, 3, 6, and 12, respectively, while "brain fog" persisted up to 12 months in 10% of patients. Spirometry and echocardiography tests returned to normal in most patients during the evaluation, and no one had substantial residual disease. Our study provides insight into the long-term effects of COVID-19 on patients' physical and mental health. Despite the lack of significant residual disease or major complications after a year of thorough follow-up, COVID-19 survivors experienced lasting symptoms and a negative impact on their QoL.

Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible?

OBJECTIVE: A preliminary definition of disease modification (DM) in lupus nephritis (LN) was recently developed focusing on long-term remission and damage prevention, with minimal treatment-associated toxicity. We aimed to further specify aspects of DM criteria in LN, assess DM achievement in a real-world setting and examine potential DM predictors and long-term outcomes. METHODS: We collected clinical/laboratory and histological inception cohort data from biopsy-proven LN patients (82% females) with ≥72 months follow-up at two joint academic centres. Specific criteria for 24-hour proteinuria, estimated glomerular filtration rate (eGFR), renal flares and glucocorticoids dose were set at three time frames (months 0-12, 13-60 and 72) to assess DM. In the first model, DM was achieved if patients fulfilled all four criteria at all three time frames (achievers). In the second model, the continued glucocorticoids reduction criterion was excluded. Logistic regression analyses were performed. Possible different trends in DM achievement between past and recent decades were also investigated. RESULTS: DM was achieved by 60% of patients, increased to 70% when glucocorticoids excluded from DM criteria. 24-hour proteinuria at 9 months predicted DM achievement (OR 0.72, 95% CI 0.53 to 0.97, p=0.03), but none of baseline characteristics. Among patients with >72 month follow-up, non-achievers had worse renal outcomes (flares, >30% proteinuria increase, eGFR decline) than achievers at the end of follow-up (median 138 months). Patients diagnosed between 1992 and 2005 were found to have significantly lower percentages of DM achievement and met less often the glucocorticoids dose reduction criterion in all three time frames, compared with those diagnosed between 2006 and 2016 (p=0.006 and p<0.01, respectively). CONCLUSIONS: DM was achieved by only 60% of LN patients in a real-life setting, partly due to lack of glucocorticoids dose target attainment, while DM failure was associated with worse long-term renal outcomes. This may imply limitations in the effectiveness or implementation of current LN treatments, supporting the need for novel therapeutic strategies.

Case report: The devil was hidden in the mastocytes - an unusually fulminant case of indolent systemic mastocytosis in a 45-year-old patient, missed for almost 20 years.

Indolent systemic mastocytosis (ISM) represents the most common form of SM, typically following a slow clinical course. While anaphylactic reactions may come up in the life course of an ISM patient, these are often moderate and do not pose a threat to patient's health. Here, we present an undiagnosed case of ISM with recurrent severe anaphylactic episodes following consumption of food and emotional stress. One of these episodes led to anaphylactic shock, necessitating temporary mechanical ventilation and intensive care unit (ICU) support. Besides hypotension, a diffuse, itchy, red rash was the only notable clinical finding. Upon recovery, we found abnormally high baseline serum tryptase level as well as 10% bone marrow (BM) infiltration by multifocal, dense clusters of CD117+/mast cell tryptase+/CD25+ mast cells (MCs), consolidating the diagnosis of ISM. Prophylactic treatment with a histamine receptor antagonist was initiated, resulting in milder episodes thereafter. Diagnosis of ISM requires a high level of suspicion; its prompt recognition and treatment are important in preventing potentially life-threatening anaphylactic episodes.

Predictors of Early Response, Flares, and Long-Term Adverse Renal Outcomes in Proliferative Lupus Nephritis: A 100-Month Median Follow-Up of an Inception Cohort.

Objective: To define predictors of response, time to response, flares, and long-term renal outcome in an inception cohort of proliferative lupus nephritis (PLN). Methods: We included 100 patients (80% female; mean age 31 ± 13 years) with biopsy-proven PLN (III, IV, III/IV + V). Clinical, laboratory, histological and therapeutical parameters were recorded at baseline, 6, 9, 12, 18, 24, 36, 72 months, time of flare, and last follow-up visit. Logistic and Cox-regression models were applied. Results: After induction treatment (69% received cyclophosphamide (CYC) and 27% mycophenolic acid (MPA)), partial (PR) or complete (CR) response was achieved in 59% (26% CR, 33% PR) and 67% (43% CR, 24% PR) of patients at 3 and 6 months, respectively; median time to PR was 3 months (IQR 5) and median time to CR was 6 months (IQR 9). Baseline proteinuria <1.5 g/day correlated with a shorter time to CR (HR 1.77) and with CR at 3, 6, and 9 months (OR 9.4, OR 5.3 and OR 3.7, respectively). During 100-month median follow-up, 33% of patients had ≥1 renal flares (median time: 38 months). Proteinuria >0.8 g/day at 12 months was associated with a higher risk of flares (OR 4.12), while MPA and mixed classes with lower risk (OR 0.14 and OR 0.13, respectively). Baseline proteinuria >2 g/day and 12-month proteinuria >0.8 g/day correlated with a shorter time to flare (HR 2.56 and HR 2.57, respectively). At the end of follow-up, 10% developed stage 3-4 chronic kidney disease (CKD), and 12% end-stage renal disease (ESRD). Twelve-month proteinuria >0.8 g/day (OR 10.8) and interstitial fibrosis/tubular atrophy >25% (OR 7.7) predicted CKD or ESRD at last visit. Conclusions: Baseline proteinuria <1.5 g/day predicted time to CR. Twelve-month proteinuria >0.8 g/day correlated with flares (ever) and time to flare and, along with baseline interstitial fibrosis/tubular atrophy >25%, predicted CKD or ESRD at the last visit.

New Insights Into an Overlooked Entity: Long-Term Outcomes of Membranous Lupus Nephritis From a Single Institution Inception Cohort.

Introduction: Pure membranous lupus nephritis (MLN) accounts for 10-20% of total cases of lupus nephritis and is generally associated with a better patient and renal survival compared to proliferative classes. Studies of MLN are limited by small sample size and heterogeneity of included populations since patients with pure MLN and those with mixed classes are usually examined together. Aim of the Study: To describe clinical and laboratory characteristics of patients with pure MLN, therapeutic regimens, response to treatment, renal relapses, and their long-term renal survival and to define prognostic factors of remission and relapse. Methods: We retrospectively studied an inception cohort of 27 patients with histologically proven pure MLN. Clinical, laboratory and therapeutical parameters were recorded at diagnosis, at different time points (3-6-9-12-18-24-36-72 months) during the course of the disease, at time of renal flare, and at last follow up visit. Results: 48.1% (13/27) of patients were treated with mycophenolic acid (MPA), 29.6% (8/27) with cyclophosphamide (CYC), and 3.7% (1/27) with cyclosporine (all in combination with corticosteroids). Five patients (18.5%) did not receive any immunosuppressive treatment. Mean duration of treatment was 4.7 ± 2.3 years. Median time to complete remission was 9 months (IQR = 7) and median time to partial remission was 4 months (IQR = 4). No clinical or laboratory parameter was found to be significantly associated with time to remission. Time to remission was not significantly affected by either of the two treatment regimens (CYC and MPA) (p = 0.43). Renal flare was observed in 6 (22%) of the 27 patients in a median time of 51 months (IQR = 63). Proteinuria >1 g/24 h at 1 year significantly correlated with risk of flare (OR 20, p = 0.02). After a median follow up period of 77 months, all patients had an eGFR > 60 ml/min/1.73 m2 (mean eGFR 100 ± 32 ml/min/1.73 m2). Conclusions: In a small cohort of patients with pure MLN, long-term renal survival was very good. With the limitation of the small sample size, we could not find any baseline clinical, biochemical or therapeutic factor that could predict time to remission. Proteinuria > 1 g/24 h at 1 year should be further examined in larger cohorts as a possible predictor of flare.

Treatment with 3-day methylprednisolone pulses in severe cases of COVID-19 compared with the standard regimen protocol of dexamethasone.

Since the outbreak of COVID-19, research has been focused on establishing effective treatments, especially for patients with severe pneumonia and hyperinflammation. The role and dose of corticosteroids remain obscure. We evaluated 58 patients with severe COVID-19 during two periods. 24 patients who received methylprednisolone pulses (250 mg/day intravenously for 3 days) were compared with 34 patients treated according to the standard dexamethasone protocol of 6 mg/day. Among non-intubated patients, the duration of hospitalization was shorter for those who received methylprednisolone pulses (9.5 vs 13.5, p<0.001). In a subgroup analysis of patients who required intubation, those treated with the dexamethasone protocol demonstrated a relative risk=1.89 (p=0.09) for dying, in contrast to the other group which showed a tendency towards extubation and discharge from the hospital. A 'delayed' need for intubation was also observed (6 vs 2 days, p=0.06). Treatment with methylprednisolone pulses significantly reduced hospitalization time. Although there was no statistically significant influence on the necessity for intubation, methylprednisolone pulses revealed a tendency to delay intubation and hospital discharges. This treatment could benefit patients in the hyperinflammatory phase of the disease.

Hypocomplementemia at Diagnosis of Pauci-immune Glomerulonephritis Is Associated With Advanced Histopathological Activity Index and High Probability of Treatment Resistance.

INTRODUCTION: Recent evidence suggests that complement activation is important in the pathogenesis of pauci-immune (PI) vasculitis. This is a retrospective investigation of the frequency of hypocomplementemia at pauci-immune glomerulonephritis (PIGN) diagnosis, in relation to vasculitic manifestations, renal histopathology, and treatment outcomes. METHODS: A total of 115 patients with biopsy-proven PIGN were categorized based on their serum complement C3 (sC3). Histopathology evaluation included activity and chronicity indexes. The primary outcome of interest was treatment resistance, defined as a progressive decline in kidney function, with persistently active urine sediment, leading to dialysis dependency or vasculitis-related death. RESULTS: In all, 20.9% of patients had low sC3 levels associated with more advanced renal impairment (P < 0.01), requiring acute dialysis (P < 0.01) more frequently compared to patients with normal sC3. Within 1 year, 85.7% of patients with normal sC3 responded to therapy, versus 58.3% of those with low sC3 (P = 0.001). The probability of treatment resistance was strongly associated with low sC3 (P = 0.004), high serum creatinine (P < 0.001), acute dialysis requirement (P < 0.001), and high histopathological score of chronicity (P < 0.01). Advanced histopathological activity was related to more intense interstitial leukocyte infiltration (P = 0.005) and higher likelihood of fibrinoid necrosis documentation in a vessel wall (P = 0.02). The probability of treatment resistance was higher in patients with low sC3 (odds ratio [OR] = 6.47, 95% confidence interval [CI] 1.47-28.35, P = 0.013), oliguria (OR = 29.57, 95% CI = 4.74-184, P < 0.0001), and high chronicity score (OR = 1.77, 95% CI = 1.23-2.54, P = 0.002). CONCLUSION: Low sC3 is emerging as an independent predictor of treatment resistance in patients with PIGN associated with higher index of histopathological activity at diagnosis compared to normal sC3.

Kidney transplantation outcomes in patients with IgA nephropathy and other glomerular and non-glomerular primary diseases in the new era of immunosuppression.

OBJECTIVES: Kidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes. METHODS: Ninety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN). RESULTS: At end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (p<0.0001) in the FSGS group, 42.1% (p = 0.17) in the IMN group, and 0% in the LN and PIGN groups (p = 0.01). IgAN recipients, who were maintained with a regimen containing tacrolimus, experienced recurrence less frequently, compared to those maintained with cyclosporine (p = 0.01). Graft loss attributed to recurrence was significantly higher in patients with FSGS versus all others. CONCLUSION: Recipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine.

The Evolution of Living Donor Nephrectomy Program at A Hellenic Transplant Center. Laparoscopic vs. Open Donor Nephrectomy: Single-Center Experience.

Since its introduction in 1995, laparoscopic nephrectomy has emerged as the preferred surgical approach for living donor nephrectomy. Given the ubiquity of the surgical procedure and the need for favorable outcomes, as it is an elective operation on otherwise healthy individuals, it is imperative to ensure appropriate preoperative risk stratification and anticipate intraoperative challenges. The aim of the present study was to compare peri-and postoperative outcomes of living kidney donors (LD), who had undergone laparoscopic nephrectomy (LDN), with a control group of those who had undergone open nephrectomy (ODN). Health-related quality of life (QoL) was also assessed using the validated SF-36 questionnaire. Data from 252 LD from a single transplant center from March 2015 to December 2020 were analyzed retrospectively. In total, 117 donors in the LDN and 135 in the ODN groups were assessed. Demographics, type of transplantation, BMI, duration of surgery, length of hospital stay, peri- and postoperative complications, renal function at discharge and QoL were recorded and compared between the two groups using Stata 13.0 software. There was no difference in baseline characteristics, nor in the prevalence of peri-and postoperative complications, with a total complication rate of 16% (mostly minor, Clavien-Dindo grade II) in both groups, while a different pattern of surgical complications was noticed between them. Duration of surgery was significantly longer in the ODN group (median 240 min vs. 160 min in LDN, p < 0.01), warm ischemia time was longer in the LDN group (median 6 min vs.2 min in ODN, p < 0.01) and length of hospital stay shorter in the LDN group (median 3 days vs. 7 days in ODN). Conversion rate from laparoscopic to open surgery was 2.5%. There was a drop in estimated glomerular filtration rate (eGFR) at discharge of 36 mL/min in the LDN and 32 mL/min in the ODN groups, respectively (p = 0.03). No death, readmission or reoperation were recorded. There was a significant difference in favor of LDN group for each one of the eight items of the questionnaire (SF1-SF8). As for the two summary scores, while the total physical component summary (PCS) score was comparable between the two groups (57.87 in the LDN group and 57.07 in the ODN group), the mental component summary (MCS) score was significantly higher (62.14 vs. 45.22, p < 0.001) in the LDN group. This study provides evidence that minimally invasive surgery can be performed safely, with very good short-term outcomes, providing several benefits for the living kidney donor, thereby contributing to expanding the living donor pool, which is essential, especially in countries with deceased-donor organ shortage.

The role of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis.

BACKGROUND: Plasma exchange (PLEX) in addition to standard immunosuppressive treatment in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AVV) remains controversial. The aim of this study is to evaluate the effect of PLEX on AVV outcomes. METHODS: Literature search was performed using Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov databases, and Google Scholar. The statistical meta-analysis and leave-one-out analysis were conducted using the Review Manager 5.3 and Open Meta-Analyst software, respectively. RESULTS: Ten studies were included in the meta-analysis comprising 1235 patients; 633 received conventional treatment and 602 were treated with PLEX in conjunction with induction therapy. PLEX was not associated with lower rates of either mortality at 3 (RR: 0.79, 95% CI: 0.19-3.25) and 12 months (RR: 0.73, 95% CI: 0.40-1.34) or ESRD at 3 (RR: 0.30, 95% CI: 0.30-2.42) and 12 months (RR: 1.32, 95% CI: 0.53-3.25). Similarly, no differences were captured concerning disease relapses (RR: 0.92, 95% CI: 0.62-1.36), the incidence of infections (RR: 1.05, 95% CI: 0.63-1.76), and severe adverse effects (RR: 1.04, 95% CI: 0.59-1.81). Time-to-event analysis revealed lower incidence of ESRD (HR: 0.71, 95% CI: 0.55-0.92) among patients who received PLEX, while the overall mortality was similar (HR: 0.96, 95% CI: 0.72-1.29) between the two groups. CONCLUSION: The present meta-analysis does not support the wide use of PLEX for the management of AAV in routine clinical practice. Future well-designed randomized controlled trials focusing on specific disease-related manifestations are necessary to reach firm conclusions about the potential efficacy of PLEX. Key Points • PLEX is not widely recommended for the management of ANCA-associated vasculitis. • PLEX performance may reduce the overall incidence of ESRD in severe ANCA-associated vasculitis. • Well-designed randomized controlled trials focusing on specific disease-related manifestations are necessary to reach firm conclusions about the potential efficacy of PLEX on AAV-related outcome.