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Background Global oxygenation can be indirectly measured by the measurement of venous oxygen saturation. Objective To estimate the value of central venous oxygen saturation (ScvO2) to predict the outcome in type 1 acute respiratory failure (ARF) patients admitted to the respiratory ICU and to assess its potential association with mortality. Patients and methods The study included 62 type 1 ARF patients admitted to respiratory ICU with indication for a central venous catheter. ScvO2 was measured from right atrium blood samples at admission, 3 and 7 days later. Arterial blood gas was assessed simultaneously. The patients were classified into three groups according to the ScvO2 level (at admission): high more than 75%, normal 65–75%, and low less than 65% (9, 34, and 19 patients, respectively). The best ScvO2 cutoff value associated with the mortality was considered the critical value of ScvO2. Acute physiology and chronic health evaluation (APACHE) II score severity, ICU, and hospital stay, and hospital mortality were reported. Results Sixty-two type 1 ARF patients with a mean age of 60±17.4 years were included. Seventy-nine percent patients had pneumonia. Mechanical ventilation was indicated in 77.4% of the patients with a mean duration of 6±3.6 days. The mean ScvO2 at day 0, 3, and 7 were 67.7±8.1, 66±11, and 69.3±9.3, respectively. The mean hospital stay was 6.8±4 days; 72.6% of the patients died in the hospital. Overall mortality in patients with low, normal, and high ScvO2 (at admission) were 42.2, 40, and 17.8%, respectively. Abnormal low and high ScvO2 was significantly related to mortality (P

Abstract Background The aquatic Acari are known as water mites and occupy a wide range of habitats. The freshwater mites, Unionicola aegyptiaca, were collected from the freshwater mussel, Caelatura aegyptiaca, River Nile, Sohag, Egypt. The present paper focuses on the structure of the cuticle and musculature of freshwater mite, U. aegyptiaca. Results Histologically, the cuticle consists of two main layers: epicuticle and procuticle. The latter divided into two sublayers, exocuticle (exo) and endocuticle (en). The musculature of the present species, U. aegyptiaca, is divided into three regions: gnathosoma, idiosoma, and legs. The muscles of the body are classified according to their position and function. Conclusion Details of muscles of gnathosoma, coxal epimerae, genital field, and legs were all described and discussed. The cuticle and musculature of U. aegyptiaca were studied by using the light microscope, and the drawings were down with the help of a camera Lucida. It is likely to note that the cuticle and musculature of freshwater mite, U. aegyptiaca, were described and discussed for the first time in Egypt.

This study included the distribution of TORCH (T. gondii, Rubella, CMV, and HSV- 2) infections among 276 pregnant women of different ages (18 – 45 years), 184 with Bad Obstetric History (BOH) and 92 with normal obstetric history. All cases were examined serologically by ELISA for the detection of IgG and IgM antibodies against TORCH pathogens. The seropositivity of TORCH infections was significantly higher in women with BOH than those of normal pregnant women with previous normal full term deliveries. As out of 184 pregnant women with BOH, the seropositivity for anti IgG and IgM for T. gondii, CMV, Rubella and HSV-2 were 66 (35.9%) and 6 (3.3%), 159 (86.4%) and 29 (15.8%), 108 (58.7%) and 3 (1.6%) and 104 (56.5%) and 20 (10.9%), respectively. Out of 92 examined normal pregnant women, the seropositivity for anti IgG and IgM for T. gondii, CMV, Rubella and HSV-2 were 38 (41.3%) and one case (1.1%) ,79 (85.9%) and 5 (5.4%), 43 (46.7%),1 (1.1%), and48 (52.2%) and 4 (4.3%), respectively. Regarding age, young ages (25-31 years) showed higher rates of seropositivity, for T.gondii, CMV and HSV-2 which was 57.1% (105/184) than older ages(39-45 years) in which it was only 1.1% (2/184).except Rubella which showed high seropositivity among all ages. Regarding occupation, housewives showed higher seropositivity(74.3%) than employed women (40.2%). With respect to period of gestation, for all agents high infection rates (45.7%) occurred during the first trimester of pregnancy and the lowest(12.5%) was recorded in third trimester stages.

This study was performed to demonstrate the effect of TORCH agents on pregnancy outcome of 84 mothers with BOD, the number of single, twice, triple, four and more miscarriages were 102 (55.4%), 50 (27.2%), 27 (14.7%) and 5 (2.7%), respectively. Out of 102 BOH pregnant women with single miscarriage, 43 (42.2%) and 2 (4.9%) were seropositive for anti T. gondii IgG and IgM, respectively, 89 (87.3%) and 17 (16.7) were seropositive for anti CMV IgG and IgM, respectively, 63 (61.8%) and 3 (2.9%) were seropositive for anti Rubella IgG and IgM, respectively and 63(61.8%) and 14(13.7) were seropositive for HSV-2 IgG and IgM, respectively. Regarding women with twice miscarriage, 1 (2.0%), 14 (28.0%) were seropositive for T. gondii anti IgG and IgM, respectively, 16 (8.0%), 43 (86.0%) were seropositive for CMV anti IgG and IgM, 29(58.0%), respectively. The IgG of anti Rubella was recorded in 29 (58.0%) no any case for anti IgM. and 29 (58%) and 3 (6.0%) were positive for HSV-2 anti IgG and IgM, respectively. The number of cases with triple miscarriages, 8 (11.1%) were seropositive for anti T. gondii IgG antibodies, while no any case was found against IgM antibodies. Only, 3 (4.2%), 22 (30.6%) were seropositive for anti CMV IgG and IgM respectively. The seropositivity of anti Rubella, anti HSV-2 IgG and IgM antibodies in group with triple miscarriages were recorded in 12 (16.7%), 10 (13.9%), 0 (0.0%) and 3 (4.2%) respectively. The number of cases with four and more miscarriages, all (100%) were seropositive for CMV anti IgG and IgM, and one (20%) for T. gondii anti IgG and IgM, while 2 (40%) and 4 (80%),were seropositive for anti Rubella and anti HSV-2 IgG, respectively. Also the results indicated that 134 (72.8%) of all examined pregnant women with BOH have history of miscarriages,14 (7.6%) congenital malformation, 13 (7.1%) intrauterine growth retardation,10 (5.4%) premature labor and 13 (7.1%) still birth. with the predominant of anti CMV IgG and IgM antibodies.

Background: Alport syndrome (AS) is one of the most common monogenic kidney disorders. Recent studies have highlighted the modifier effect of variants involving podocyte and non-collagenous extracellular matrix (ECM) proteins in AS., Methods: We report a case series of eight patients with genetically proven AS and simultaneous variants involving podocyte and non-collagenous ECM proteins. Our aim is to describe the influence of such variants on the phenotype of patients with AS., Results: We identified 10 different type IV collagen variants. Patients were diagnosed with autosomal dominant (3/8), autosomal recessive (2/8), digenic (2/8) and X-linked AS (1/8). There were eight different variants involving podocyte and non-collagenous ECM proteins. The genes involved were CRB2, LAMA5, LAMB2, NUP107, MYO1E and PLCE1. Four patients (LAMB2, LAMA5 and PLCE1 variants) presented with nephrotic syndrome or nephrotic range proteinuria. Two patients had hearing loss. Most patients (7/8) had a family history of kidney disease. Two patients (LAMB2 and LAMA5 variants) were diagnosed with focal segmental glomerulosclerosis. Two patients developed end-stage kidney disease (LAMA5, MYO1E and NUP107 variants)., Conclusions: Although mutations of podocyte and ECM proteins do not have phenotypic expression in monoallelic form, the presence of such variants could explain the phenotypic variability of AS.

Background: Disease-related knowledge of people with multiple sclerosis (MS) can influence self-management, coping, treatment adherence, and clinical health outcomes. Studies assessing MS patients' knowledge are scarce., Objectives: The aim of this study was to evaluate the awareness and knowledge of Lebanese MS patients regarding their disease and identify the factors associated with poor knowledge., Methods: This cross-sectional, multicenter, survey-based study was conducted between June and September 2023 among Lebanese MS patients with confirmed diagnosis. MS knowledge was assessed using the validated MS knowledge questionnaire (MSKQ-25)., Results: A total of 350 patients were included. Most (92.3 %) were diagnosed with relapsing-remitting MS, and 65.1 % were female with a mean age of 39.4 ± 11.4 years. The mean MSKQ-25 score was 15.1 ± 3.9. The mean percentage of correct answers was 60.4 % ± 15.9, with 65.1 % scoring ≥60 %. Multivariate analysis identified higher education (p = 0.004) and residence in Beirut (p = 0.025) as significant predictors of increased knowledge levels., Conclusion: Lebanese MS patients demonstrated adequate disease knowledge. Higher education and residing in the capital Beirut were key contributors to improved knowledge., Competing Interests: Declaration of competing interest Maya Zeineddine has received honororia for lectures from Biologix, Biogen, Janssen, Hikma Pharmaceuticals, Novartis, Merck, Roche and Sanofi-Genyme. She received travel grants from Novartis, Merck and Roche and a research grant from Biogen. She has no conflict of interest related to this study., (Copyright © 2024. Published by Elsevier B.V.)

While the Banff classification dichotomizes kidney allograft rejection based on the localization of the cells in the different compartments of the cortical kidney tissue [schematically interstitium for T cell mediated rejection (TCMR) and glomerular and peritubular capillaries for antibody-mediated rejection (AMR)], there is a growing evidences that subtyping the immune cells can help refine prognosis prediction and treatment tailoring, based on a better understanding of the pathophysiology of kidney allograft rejection. In the last few years, multiplex IF techniques and automatic counting systems as well as transcriptomics studies (bulk, single-cell and spatial techniques) have provided invaluable clues to further decipher the complex puzzle of rejection. In this review, we aim to better describe the inflammatory infiltrates that occur during the course of kidney transplant rejection (active AMR, chronic active AMR and acute and chronic active TCMR). We also discuss minor components of the inflammatory response (mastocytes, eosinophils, neutrophils, follicular dendritic cells). We conclude by discussing whether the over simplistic dichotomy between AMR and TCMR, currently used in clinical routine, remains relevant given the great diversity of immune actors involved in rejections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Terinte-Balcan, Lebraud, Zuber, Anglicheau, Ismail and Rabant.)

Fabry disease (FD) is an X-linked rare disorder caused by mutations in the GLA gene. Women with FD have been less enrolled in studies and less treated compared with men. The aim of the present study is to describe the complete phenotype of the women cohort with FD diagnosed and evaluated in Romania and compare it to the male population. This study included all consecutive patients diagnosed with FD referred to the Expert Center for Rare Genetic Cardiovascular Diseases between 2014-2023 which included 73 consecutive Romanian FD patients: 41 women (56.2%) and 32 men (43.8%) from 33 unrelated families. Women with FD were diagnosed later and had a later symptom onset. Comparing with men, women were less often symptomatic, but with similar symptom severity. They had similar ophthalmologic and ENT involvement, but less angiokeratomas. Both women and men had similar heart failure symptoms, which were usually mild to moderate, with no difference between the age of developing of the heart failure symptoms. There were also similar rates of acroparesthesia and stroke between sexes, but women presented less renal involvement, with less requirement for renal transplant. This study demonstrates that women with Fabry disease are not just carriers of the disease, they can present symptoms as severe as men, and they have less or later access to pathogenic therapy. Further studies with more female participations are needed to better understand the burden of Fabry disease in women., (© 2024 Adriana Mursă et al., published by Sciendo.)

Introduction: Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with challenges, such as drug interactions between immunosuppression and antiretroviral (ARV) therapy. In our country, no KT has been performed thus far in this category of patients., Case Presentation: We present the case of a 29-year-old female patient with HIV and end-stage renal disease (ESRD) who performed a KT from a related living donor in March 2022. KT immediate evolution was favorable. No transplant-related complications were reported. HIV viral load remained undetectable and CD4+ T cells were constantly > 500 cell/ μL, during the 18 months of follow-up. The main challenge in our case was the drug interaction between the protease inhibitor-based regimen and tacrolimus. This led to tacrolimus overdose, and, subsequently, change in ARV therapy. ARV switching was performed on a regimen based on integrase inhibitor and nucleoside reverse transcriptase inhibitors. After the ARV change, the therapeutic level of tacrolimus was easily reached and maintained. Kidney graft function remained normal during follow-up, despite tacrolimus overexposure, and no rejection or anti-HLA antibodies were observed. Another challenge was related to the donor's hepatitis C virus status (positive antibodies, negative nucleic acid test). The recipient did not develop seroconversion or detectable viremia at 3-, 6-, 12- and 18-months post-KT., Conclusion: We reported the first case of a successful KT in an ESRD patient with HIV in Romania, in whom the post-transplant evolution was favorable., (© 2024 Bogdan Marian Sorohan et al., published by Sciendo.)

Xanthogranulomatous pleuritis is an extremely rare pathological entity, characterized by the infiltration of foamy cells and multinucleated giant cells within the pleural space. This condition often mimics infectious and neoplastic processes, presenting significant diagnostic challenges. This report details the first documented case of xanthogranulomatous pleuritis induced by recurrent biliothorax due to a biliopleural fistula, presenting a unique clinical scenario. We describe the clinical presentation, diagnostic hurdles, and both the surgical and medical management of this case. The discovery of biliothorax, evidenced by pleural fluid bilirubin levels that exceed serum bilirubin levels, underscores the importance of considering biliothorax in the differential diagnosis of recurrent pleural effusions, particularly in patients with a history of trauma. This case emphasizes the need for heightened awareness and a multidisciplinary approach in the diagnosis and treatment to effectively manage this complex condition and prevent recurrence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Competing Interests: Competing interests: None declared.

Background: Alport syndrome (AS) is a common and heterogeneous genetic kidney disease, that often leads to end-stage kidney disease (ESKD)., Methods: This is a single-center, retrospective study that included 36 adults with type IV collagen (COL4) mutations. Our main scope was to describe how genetic features influence renal survival., Results: A total of 24 different mutations were identified, of which eight had not been previously described. Mutations affecting each of the type IV collagen α chains were equally prevalent (33.3%). Most of the patients had pathogenic variants (61.1%). Most patients had a family history of kidney disease (71%). The most prevalent clinical picture was nephritic syndrome (64%). One-third of the subjects had extrarenal manifestations, 41.6% of patients had ESKD at referral, and another 8.3% developed ESKD during follow-up. The median renal survival was 42 years (95% CI, 29.98-54.01). The COL4A4 group displayed better renal survival than the COL4A3 group ( p = 0.027). Patients with missense variants had higher renal survival ( p = 0.023). Hearing loss was associated with lower renal survival ( p < 0.001)., Conclusions: Patients with COL4A4 variants and those with missense mutations had significantly better renal survival, whereas those with COL4A3 variants and those with hearing loss had worse prognoses.

Background: There is a clear need to refine the histological assessment in IgA Nephropathy (IgAN). We sought to investigate the clinical significance of the light microscopy (LM) pattern of glomerular injury and of the intensity of mesangial C3 staining in IgAN., Methods: We conducted a retrospective, observational study that included all patients with biopsy-proven primary IgAN that had at least 12 months of follow-up. The LM pattern of glomerular injury was reevaluated based on a modified HAAS classification. Mesangial C3 deposition by immunofluorescence (IF) staining was scored semi-quantitatively. The study primary composite endpoint was defined as doubling of serum creatinine or ESRD (dialysis, renal transplant or eGFR < 15 ml/min). The secondary study endpoint was eGFR decline per year., Results: This cohort included 214 patients with IgAN (mean age, 41.4 ± 12.6 years), with a mean eGFR and median 24-h proteinuria of 55.2 ± 31.5 ml/min/1.73m 2 and 1.5 g/day (IQR:0.8-3.25), respectively. The most frequent LM pattern was the mesangioproliferative (37.4%), followed by the sclerotic (22.5%) and proliferative/necrotizing patterns (21.4%). Regarding the IF findings, mild-moderate and intense mesangial C3 staining was present in 30.6% and 61.1% of patients, respectively. Those with sclerosing and crescentic patterns had the worst renal survival (5-year renal survival of 48.8% and 42.9%) and the highest rate of eGFR change/year (-2.32 ml/min/y and - 2.16 ml/min/y, respectively) compared to those with other glomerular patterns of injury. In addition, those with intense C3 staining reached the composite endpoint more frequently compared to those without intense C3 staining (35.5% vs. 21.4%, p = 0.04). After multivariate adjustment, patients with crescentic and sclerosing patterns had a 3.6-fold and 2.1-fold higher risk for the composite endpoint compared to those with mesangioproliferative pattern, while an intense mesangial C3 deposition being also associated with a worse renal outcome (HR, 3.33; 95%CI, 1.21-9.2)., Conclusions: We have shown that the LM pattern of glomerular injury and the intensity of mesangial C3 deposition might stratify more accurately the renal outcome in patients with IgAN., (© 2024. The Author(s).)

Background: Metabolic acidosis (MA) is frequently associated with chronic kidney disease (CKD) progression. Our aim was to compare the effect of oral sodium citrate (SC) with that of oral sodium bicarbonate (SB) on renal function and serum bicarbonate correction, as well as to evaluate their safety profile in patients with MA of CKD., Methods: We conducted a prospective, single-center, randomized 1:1, parallel, controlled, unblinded clinical trial of 124 patients with MA and CKD stages 3b and 4. The primary outcome was the mean change in estimated glomerular filtration rate (eGFR). The secondary outcomes were mean change in serum bicarbonate level, eGFR decrease by 30%, eGFR decrease by 50%, dialysis, death or prolonged hospitalization, and a combined endpoint., Results: No significant difference was found between the groups in terms of mean eGFR change [adjusted mean difference = -0.99 mL/min/1.73 m2 (95% CI: -2.51 to 0.93, P = .20)]. We observed a mean serum bicarbonate change of 6.15 mmol/L [(95% CI: 5.55-6.74), P < .001] in the SC group and of 6.19 mmol/L [(95% CI: 5.54-6.83), P < .001] in the SB group, but no significant difference between the 2 groups [adjusted mean difference = 0.31 mmol/L (-0.22 to 0.85), P = .25]. Cox proportional hazard analysis showed similar risks regarding eGFR decrease by 30% (P = .77), eGFR decrease by 50% (P = .50), dialysis (P = .85), death or prolonged hospitalization (P = .29), and combined endpoint (P = .57). Study drug discontinuation due to adverse events was significantly more common in the SB group (17.7% vs 4.8%, P = .02)., Conclusions: SC and SB have a similar effect on kidney function decline, both improve serum bicarbonate level, but SB is associated with higher rates of medication discontinuation due to adverse events., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Nephrotic edema stands out as one of the most common complications of nephrotic syndrome. The effective management of hypervolemia is paramount in addressing this condition. Initially, "the underfill hypothesis" suggested that proteinuria and hypoalbuminemia led to fluid extravasation into the interstitial space, causing the intravascular hypovolemia and activation of neurohormonal compensatory mechanisms, which increased the retention of salt and water. Consequently, the recommended management involved diuretics and human-albumin infusion. However, recent findings from human and animal studies have unveiled a kidney-limited sodium-reabsorption mechanism, attributed to the presence of various serine proteases in the tubular lumen-activating ENaC channels, thereby causing sodium reabsorption. There is currently no standardized guideline for diuretic therapy. In clinical practice, loop diuretics continue to be the preferred initial choice. It is noteworthy that patients often exhibit diuretic resistance due to various factors such as high-sodium diets, poor drug compliance, changes in pharmacokinetics or pharmacodynamics, kidney dysfunction, decreased renal flow, nephron remodeling and proteasuria. Considering these challenges, combining diuretics may be a rational approach to overcoming diuretic resistance. Despite the limited data available on diuretic treatment in nephrotic syndrome complicated by hypervolemia, ENaC blockers emerge as a potential add-on treatment for nephrotic edema.

Antimicrobials are administered in livestock for different uses leading to milk contamination and several undesirable effects. Because there is a lack of surveillance of antimicrobial residues (AMRs) in milk and dairy products in Lebanon, this study aims to determine the occurrence of AMRs in 90 Lebanese samples of milk and labneh (concentrated yoghurt). Multi-residue screening methods with suitable sample preparations were applied to detect 71 AMRs in milk and labneh, respectively, using LC-MS/MS. Of the total number of samples, 71% was contaminated with AMRs and (fluoro)quinolones and macrolides were the most detected families. Additional confirmation tests proved that 6.7% of the milk samples were non-compliant for the macrolides tilmicosin, tulathromycin and spiramycin. Moreover, some labneh prepared from contaminated milk samples was analysed to determine the fate of AMRs during the manufacturing process. The results showed that some AMRs could be concentrated, eliminated or degraded, based on their physicochemical characteristics.

Background: We sought to evaluate the long-term effects of COVID-19 on renal function in patients with biopsy-proven kidney diseases., Methods: A total of 451 patients with biopsy-proven kidney disease and at least 12 months of follow-up subsequent to COVID-19 pandemic onset were included in the study. The primary study endpoint was a composite of a persistent decline of more than 30% in eGFR or ESRD., Results: 23.1% of patients had COVID-19 during a follow-up period of 2.5 y (0.8-2.6), while 17.6% of patients reached the composite endpoint. Those with COVID-19 were more likely to reach the composite endpoint [26.7% vs. 14.8%; OR, 2.1 (95%CI, 1.23-3.58), p = 0.006). There was a significant eGFR change in the first year of follow-up between the two study groups [-2.24 (95%CI,-4.86; 0.37) vs. +2.31 (95%CI, 0.78; 3.85) ml/min, p = 0.004], with an adjusted mean difference of -4.68 ml/min (95%CI,-7.7; -1.59)(p = 0.03). The trend for worse renal outcomes remained consistent in patients with IgAN, MN and FSGS, but not in those with LN. After multivariate adjustment, the independent predictors of the composite endpoint were baseline eGFR (HR, 0.94; 95%CI, 0.92-0.95), COVID-19 (HR, 1.91; 1.16-3.12) and male gender (HR, 1.64; 95%CI, 1.01-2.66). In multivariate linear regression analysis, COVID-19 independently determined a reduction of eGFR at 12 months by 4.62 ml/min/1.73m2 (β coefficient, -4.62; 95%CI, -7.74 to -1.5, p = 0.004)., Conclusions: There is a significant impact of COVID-19 on long-term renal function in patients with biopsy-proven kidney diseases, leading to a greater decline of eGFR and a worse renal survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Obrișcă et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The presence of anti-Glutathione S-transferase T1 (GSTT1) antibodies (abs) has been hypothesized as a pathogenic contributor in antibody-mediated rejection (AMR)., Methods: We aimed to evaluate the relationship between genetic variants of GSTT1, anti-GSTT1 abs and AMR in a cohort of 87 kidney transplant (KTx) patients using Immucor's non-HLA Luminex assay. Patients were classified according to biopsy-proven AMR and HLA-DSA status: AMR with positive anti-HLA-DSAs (AMR/DSA+, n = 29), AMR but no detectable anti-HLA-DSAs (AMR/DSA-, n = 28) and control patients with stable allograft function and no evidence of rejection (n = 30)., Results: At an MFI cut-off of 3000, the overall prevalence of anti-GSTT1 abs was 18.3%. The proportion of patients with anti-GSTT1 abs was higher in the AMR/DSA- group (25%), compared to the control (13.3%) and AMR/DSA+ group (3.4%) (p = 0.06). Among patients with anti-GSTT1 abs, the MFI was higher in AMR/DSA- and GSTT1-Null patients. Of 81 patients who underwent GSTT1 genotyping, 19.8% were homozygotes for the null allele (GSTT1-Null). GSTT1-Null status in the transplant recipients was associated with the development of anti-GSTT1 abs (OR, 4.49; 95%CI, 1.2-16.7). In addition, GSTT1-Null genotype (OR 26.01; 95%CI, 1.63-404) and anti-GSTT1 ab positivity (OR 14.8; 95%CI, 1.1-190) were associated with AMR. Within AMR/DSA- patients, the presence of anti-GSTT1 abs didn't confer a higher risk of failure within the study observation period., Conclusion: The presence of anti-GSTT1 abs and GSTT1-Null genotype is associated with AMR, but do not appear to lead to accelerated graft injury in this cohort of early allograft injury changes, with a limited period of follow-up., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of registration 14/02/2020). Patients were treated with Budesonide at a dose of 9 mg/day for 12 months, subsequently tapered to 3 mg/day for another 12 months. The primary endpoints were change of eGFR and proteinuria at 12, 24 and 36 months. The study cohort had a mean eGFR and 24-h proteinuria of 59 ± 24 ml/min/1.73m 2 and 1.89 ± 1.5 g/day, respectively. Treatment with budesonide determined a reduction in proteinuria at 12-, 24- and 36-months by -32.9% (95% CI - 53.6 to - 12.2), - 49.7% (95% CI - 70.1 to - 29.4) and - 68.1% (95% CI - 80.6 to - 55.7). Budesonide determined an eGFR preservation corresponding to a 12-, 24- and 36-months change of + 7.68% (95% CI - 4.7 to 20.1), + 7.42% (95% CI - 7.23 to 22.1) and + 4.74% (95%CI - 13.5 to 23), respectively. The overall eGFR change/year was + 0.83 ml/min/y (95% CI - 0.54 to 4.46). Budesonide was well-tolerated, and treatment emergent adverse events were mostly mild in severity and reversible. Budesonide was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria and preserving renal function over 36 months of therapy., (© 2023. The Author(s).)

Background: Data on diuretic treatment in nephrotic syndrome (NS) are scarce. Our goal was to assess the non-inferiority of the combined oral diuretics (furosemide/hydrochlorothiazide/amiloride) compared to intravenous (i.v.) furosemide in patients with NS and resistant edema., Methods: We conducted a prospective randomized trial on 22 patients with resistant nephrotic edema (RNE), defined as hypervolemia and a FENa < 0.2%. Based on a computer-generated 1:1 randomization, we assigned patients to receive either intravenous furosemide (40 mg bolus and then continuous administration of 5 mg/h) or oral furosemide (40 mg/day) and hydrochlorothiazide/amiloride (50/5 mg/day) for a period of 5 days. Clinical and laboratory measurements were performed daily. Hydration status was assessed by bioimpedance on day 1 and at the end of day 5 after treatment initiation. The primary endpoint was weight change from baseline to day 5. Secondary endpoints were hydration status change measured by bioimpedance and safety outcomes (low blood pressure, severe electrolyte disturbances, acute kidney injury and worsening hypervolemia)., Results: Primary endpoint analysis showed that after 5 days of treatment, there was a significant difference in weight change from baseline between groups [adjusted mean difference: -3.33 kg (95% CI: -6.34 to -0.31), p = 0.03], with a higher mean weight change in the oral diuretic treatment group [-7.10 kg (95% CI: -18.30 to -4.30) vs. -4.55 kg (95%CI: -6.73 to -2.36)]. Secondary endpoint analysis showed that there was no significant difference between groups regarding hydration status change [adjusted mean difference: -0.05 L (95% CI: -2.6 to 2.6), p = 0.96], with a mean hydration status change in the oral diuretic treatment group of -4.71 L (95% CI: -6.87 to -2.54) and -3.91 L (95% CI: -5.69 to -2.13) in the i.v. diuretic treatment group. We observed a significant decrease in adjusted mean serum sodium of -2.15 mmol/L [(95% CI: -4.25 to -0.05), p = 0.04]), favored by the combined oral diuretic treatment [-2.70 mmol/L (95% CI: -4.89 to -0.50) vs. -0.10 mmol/L (95%CI: -1.30 to 1.10)]. No statistically significant difference was observed between the two groups in terms of adverse events., Conclusions: A combination of oral diuretics based on furosemide, amiloride and hydrochlorothiazide is non-inferior to i.v. furosemide in weight control of patients with RNE and a similar safety profile.

(1) Background. Hepatitis C infection often leads to extrahepatic manifestations, including cryoglobulinemic vasculitis. This systematic review aimed to assess the efficacy and safety of rituximab in treating hepatitis C-associated cryoglobulinemic vasculitis. (2) Methods. Following PRISMA guidelines, databases were searched for relevant studies. Eligibility criteria included studies on hepatitis C-associated cryoglobulinemic vasculitis treated with rituximab. (3) Results. Nine studies met the eligibility criteria and were included in this analysis. Rituximab was commonly administered at 375 mg/m 2 weekly for one month. The results consistently demonstrated the efficacy of rituximab, whether as a standalone treatment or as part of a therapeutic regimen. The combination of rituximab with Peg-IFN-α and ribavirin significantly increased the complete response rate compared to Peg-IFN-α and ribavirin alone (54.5% vs. 33.3%, p < 0.05). The 3-year sustained response rate was notably higher in the rituximab combination group (83.3% vs. 40%). In another trial, rituximab achieved remission in 83.3% of patients at 6 months, compared to only 8.3% in the control group. The efficacy of rituximab was supported by long-term experience, with clinical benefits in patients with severe cryoglobulinemic vasculitis, including those resistant to standard therapies. Mild adverse events were generally reported, with rare severe reactions in some studies. (4) Conclusions: In conclusion, rituximab appeared to be effective and safe in managing hepatitis C-associated cryoglobulinemic vasculitis, either alone or with antiviral therapy.

Tuberous sclerosis complex is a rare multisystem genetic disorder characterized by multiorgan involvement, frequently associated with intellectual impairment and epilepsy. The aim of our study was to describe the neurological and dermatological manifestations of TSC in 32 adult patients (of whom 19 were females) who attended the Neurology and Nephrology Clinics of Fundeni Clinical Institute in Romania from 2015 to 2020. Seventeen patients were diagnosed with epilepsy, nine patients had intellectual impairment, and complete neuroimaging was available for twenty-two patients. As expected, the most frequent dermatological lesions were cutaneous angiofibromas in 20 patients, but with a lower frequency than described in the current literature. Statistical analysis was performed considering the small number of patients. Cortical tubers in neuroimaging seemed to be associated with the diagnosis of epilepsy, while subependymal nodules represented a risk factor for intellectual impairment. Males showed a larger number of dermatological types of lesions, especially café -au-lait patches. Interestingly, we found a statistically significant positive association between epilepsy and the presence of cutaneous angiofibromas, as well as total dermatological involvement. Females had significantly higher Charlson comorbidity index scores, indicating a higher burden of disease. Everolimus seemed to be a well-tolerated treatment and showed promising results in controlling epileptic seizures alone in two patients. More studies, with the inclusion of a larger number of patients, are needed to confirm these results.

Purpose of Study: The purpose of this review is to provide the current state of immunosuppression therapy in kidney transplant recipients (KTR) with HIV and to discuss practical dilemmas to better understand and manage these patients., Recent Findings: Certain studies find higher rates of rejection, which raises the need to critically assess the approach to immunosuppression management in HIV-positive KTR. Induction immunosuppression is guided by transplant center-level preference rather than by the individual patient characteristics. Earlier recommendations expressed concerns about the use of induction immunosuppression, especially utilizing lymphocyte-depleting agents; however, updated guidelines based on newer data recommend that induction can be used in HIV-positive KTR, and the choice of agent be made according to immunological risk. Likewise, most studies point out success with using first-line maintenance immunosuppression including tacrolimus, mycophenolate, and steroids. In selected patients, belatacept appears to be a promising alternative to calcineurin inhibitors with some well established advantages. Early discontinuation of steroids in this population carries a high risk of rejection and should be avoided., Summary: Immunosuppression management in HIV-positive KTR is complex and challenging, mainly because of the difficulty of maintaining a proper balance between rejection and infection. Interpretation and understanding of the current data towards a personalized approach of immunosuppression could improve management in HIV-positive KTR., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hantavirus infection is a rare zoonosis in South-Eastern Europe. Depending on the serotype involved, the virus can cause hemorrhagic fever with renal syndrome which is also known as endemic nephropathy, and cardiopulmonary syndrome. Prompt diagnosis of the disease is essential for reducing the risk of severe manifestations and complications like chronic kidney disease, secondary hypertension or even death because there is no specific treatment or vaccine approved. The present study reported two cases of hemorrhagic fever with renal syndrome diagnosed in the Department of Nephrology of The Fundeni Clinical Institute (Romania). In both patients, kidney needle biopsy played a major role in establishing the diagnosis. The difficulties encountered in diagnosing this disease were also emphasized, taking into consideration the rarity of this infection in South-Eastern Europe. The key literature data on the epidemiology, pathogenesis and management of this infection were further reviewed., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Lupuşoru et al.)

BACKGROUND Hemorrhagic cholecystitis is a rare cause of abdominal pain, which can result from malignancy, bleeding, or trauma. The presentation, which includes right upper-quadrant pain, nausea, and vomiting, can overlap with other disease states, thereby rendering the diagnosis challenging. CASE REPORT We describe a patient taking apixaban wo had paroxysmal atrial fibrillation with history of joint pain on long-term steroids who developed hemorrhagic cholecystitis following an episode of pneumonia secondary to SARS-CoV-2 virus (COVID-19) infection. The hospital COVID-19 pneumonia protocol included the administration of steroids and symptomatic care. Following discharge, he presented to our hospital with a sudden onset of severe abdominal pain and distention accompanied by elevated liver enzymes and a low hemoglobin level of 78 g/L. Magnetic resonance cholangiopancreatography revealed a distended gallbladder and intraluminal layering, early subacute blood products, and increased wall thickness, which was thought to represent non-calcular hemorrhagic cholecystitis. Furthermore, a stable 18×16×20 mm cyst in the tail of the pancreas was also located posteriorly, with indentation to the splenic vein. The patient was managed conservatively, and the pain subsided on day 3 after admission. CONCLUSIONS Hemorrhagic cholecystitis is rarely reported with the use of the direct oral anticoagulants (DOACs). In our case the combination of a recent COVID-19 hospitalization, steroid use, and possible pancreatic cancer (CA 19-9 288.4 kU/L) may have contributed to such incidence in the setting of apixaban utilization; however, it is not possible to make definitive correlations. Investigating hemorrhagic cholecystitis in the setting of DOAC use in patients with multiple risk factors such as those that existed in our patient is imperative for proper diagnosis and management.

Background: The occurrence of autoantibodies in human immunodeficiency virus (HIV)-infected patients has been previously reported, with a prevalence ranging from 20 to 83%. There are also a few reports of clinically relevant autoantibody profiles in HIV-positive patients that lead to true systemic autoimmune disease; these possible life-threatening diseases have to be considered and treated accordingly., Case Presentation: Here, we present the case of a 29-year-old female patient with a history of well-controlled HIV infection in the last 6 years who was admitted to our department for the evaluation of acute kidney injury and nephrotic syndrome with active urinary sediment. A diagnosis of systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with renal and pulmonary involvement was established. The patient was treated with cyclophosphamide, rituximab and tapering glucocorticoids,and the diffuse alveolar hemorrhage resolved, but the evolution of kidney function was unfavorable, which led to the need to initiate hemodialysis. We highlight the importance of establishing the correct diagnosis, treating the disease accordingly and the possible clinical issues that can appear in a patient with HIV infection during immunosuppressant treatment as induction treatment. Additionally, we performed a thorough literature review of ANCA positivity in HIV-infected patients to properly understand the current evidence., Conclusions: Although it is not clear whether HIV infection and AAV are causally or coincidentally related, the possibility of this systemic autoimmune phenomenon should be acknowledged by physicians to establish the correct diagnosis and treat the disease accordingly by maintaining a balance between the risks and benefits of immunosuppression in this category of patients, with treatment decisions being made by the members of a multidisciplinary team in centers with experience in AAV., (© 2023. The Author(s).)

The most common manifestation of skeletal tuberculosis is tuberculosis spondylitis. Symptoms may progress insidiously from back pain to cause many severe complications. Early diagnosis and management of spinal tuberculosis have special importance in prevention. We report a case of a 24-year-old female who was diagnosed with tuberculous spondylitis, complicated with psoas abscess and grade 1/5 of lower limb weakness. The patient was treated with anti-tuberculous drugs and underwent surgical debridement, interbody fusion and internal fixation accompanied by fibular autografting using a posterior-only approach and supplemental posterior spinal stabilisation on an infected background. Within 14 years of follow-up, full bone graft spinal fusion has been achieved with no major complications. According to its clinical efficacy and feasibility, this procedure is suggested to be an alternative treatment for Pott's disease., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.)

While community participation may serve as a vehicle to improve health and socioeconomic outcomes for residents in poor communities, little research exists on the individual factors that influence community participation, particularly in contexts where violence is exceptionally high. This study examined the relationship between sociodemographic characteristics, perceptions, and experiences of violence, neighborhood attachment, and community participation in a low-income, under-resourced neighborhood in Johannesburg South Africa. The study used baseline data from 300 randomly selected households and multiple linear regression to assess the relationship between individual factors and community participation. The results suggest a high level of community participation, with religious organizational membership the most common. Being female, employed, and fear of violent crime were positively associated with community participation. Future research should include mixed methods and transdisciplinary research approaches for building our understandings of social justice and transformation-oriented community participation., (© 2022 The Authors. Journal of Community Psychology published by Wiley Periodicals LLC.)

(1) Background: We sought to investigate the impact of the COVID-19 pandemic in patients with lupus nephritis (LN); (2) Methods: A total of 95 patients with LN actively monitored in our department between 26 February 2020, when the first case of COVID-19 was diagnosed in Romania, and 1 May 2021, were included in the study. Multivariate logistic regression analysis was performed to identify the independent risk factors for SARS-CoV-2 infection; (3) Results: A total of 15 patients (15.8%) had a confirmed SARS-CoV-2 infection during a total follow-up time of 105.9 patient-years (unadjusted incidence rate: 14.28 SARS-CoV-2 infections per 100 patient-years). Median time to SARS-CoV-2 infection was 9.3 months (IQR: 7.2-11.3). The majority of patients had a mild form of SARS-CoV-2 infection (73.3%), while the remaining had moderate forms. None of the patients had a severe infection or a SARS-CoV-2-related death. The most frequent symptom was fatigue (73.3%), followed by loss of taste/smell (53.3%) and fever (46.7%). Forty percent of those with SARS-CoV-2 infection were hospitalized for a median 11.5 days (IQR:3.75-14). In the multivariate logistic regression analysis, a current oral corticosteroid dose ≥ 15 mg/day was associated with a 7.69-fold higher risk (OR, 7.69; 95%, 1.3-45.46), while the use of hydroxychloroquine was associated with a 91% lower risk for a SARS-CoV-2 infection (OR, 0.09; 95%CI, 0.01-0.59). (4) Conclusions: Our study confirms that the SARS-CoV-2 infection-associated morbidity might only be moderately increased in patients with LN. The current oral corticosteroid dose was the only independent predictor of infection occurrence, while use of hydroxychloroquine was associated with a protective effect.

Tuberculosis (TB) in kidney transplant (KT) recipients is an important opportunistic infection with higher incidence and prevalence than in the general population and is associated with important morbidity and mortality. We performed an extensive literature review of articles published between 1 January 2000 and 15 June 2022 to provide an evidence-based review of epidemiology, pathogenesis, diagnosis, treatment and outcomes of TB in KT recipients. We included all studies which reported epidemiological and/or outcome data regarding active TB in KT, and we approached the diagnostic and treatment challenges according to the current guidelines. Prevalence of active TB in KT recipients ranges between 0.3-15.2%. KT recipients with active TB could have a rejection rate up to 55.6%, a rate of graft loss that varies from 2.2% to 66.6% and a mortality rate up to 60%. Understanding the epidemiological risk, risk factors, transmission modalities, diagnosis and treatment challenges is critical for clinicians in providing an appropriate management for KT with TB. Among diagnostic challenges, which are at the same time associated with delay in management, the following should be considered: atypical clinical presentation, association with co-infections, decreased predictive values of screening tests, diverse radiological aspects and particular diagnostic methods. Regarding treatment challenges in KT recipients with TB, drug interactions, drug toxicities and therapeutical adherence must be considered.

Donor specific anti-HLA antibodies (DSA) and donor-derived cell-free DNA (dd-cfDNA) have lead to substantial progress in the non-invasive monitoring of the renal allograft by being able to detect or rule out subclinical rejection and guide immunosuppressive changes. In this study we sought to analyze the clinical, de novo DSA (dnDSA) and histological determinants of dd-cfDNA levels. The study included a cohort of stable renal function kidney transplant (KT) recipients who underwent anti-HLA dnDSA and dd-cfDNA testing between September 2017-December 2019. Statistical models were constructed to detect association with predictors of dd-cfDNA levels and other clinical characteristics. 171 renal allograft recipients were tested for dd-cfDNA and dnDSA at a median 1.06 years posttransplant (IQR: 0.37-4.63). Median dd-cfDNA was 0.25% (IQR: 0.19-0.51), 18.7% of patients having a dd-cfDNA ≥ 1%. In a multivariate linear regression model the presence of dnDSA MFI ≥ 2500 was the best independent determinant of dd-cfDNA level (p < 0.001). Among patients tested, 54 had concurrent dd-cfDNA determination at the time of an allograft biopsy. dd-cfDNA had an AUC of 0.82 (95% CI 0.69-0.91; p < 0.001) and of 0.96 (95% CI 0.87-0.99) to discriminate any rejection and ABMR, respectively. After multivariate adjustment, the models that included ABMR (R = 0.82, R 2  = 0.67, p < 0.001), or ptc (R = 0.79, R 2  = 0.63, p < 0.001) showed the best correlation with dd-cfDNA level. We are confirming a strong association of dd-cfDNA with dnDSA and underlying alloimmune-mediated injury in renal allograft recipients in a cohort of patients with unsuspecting clinical characteristics for rejection and excellent allograft function. Our findings support the need for noninvasive biomarker surveillance in KT recipients and we propose that dd-cfDNA may complement dnDSA screening., (© 2022. The Author(s).)

Distal renal tubular acidosis (DRTA) has been reported in association with autoimmune diseases, such as Sjögren's syndrome, systemic lupus erythematosus (SLE), autoimmune hepatitis, primary biliary cirrhosis, rheumatoid arthritis and autoimmune thyroiditis. Whether we talk about the complete or incomplete form of DRTA associated with autoimmune diseases, the real incidence is unknown because asymptomatic patients usually are not identified, and most of the reported cases are diagnosed due to severe symptoms secondary to hypokalemia, a frequent finding in these cases. The mechanisms involved in DRTA in patients with autoimmune diseases are far from being fully elucidated and most of the data has come from patients with Sjögren's syndrome. This review will present different hypotheses raised to explain this association. Also, aiming for a better understanding of the association between autoimmune diseases and DRTA, our review summarizes data from 37 case reports published in the last five years. We will emphasize data regarding clinical presentation, biological alterations, treatment and outcome. A very important question is whether immunosuppressive therapy is helpful in DRTA associated with autoimmune diseases. Because the pathology is rather rare, treatment is not standardized, and reported results are often contradictory. Corticosteroids are frequently used, but multiple other immunosuppressive drugs have been proposed and will be approached in this review.

Background: The aim of this study is investigate the antimicrobial effect of plant oils against bacterial strains isolated from neonatal asymptomatic bacteriuria (ABU) and to evaluate the antiseptic effect of the most potent one., Methods: The antimicrobial effect of 17 plant oils were tested against 15- gram-negative bacterial strains recovered from cases of neonatal ABU (11 Escherichia. coli, 3 Klebsiella pneumonia, and 1 Pseudomonas aeruginosa) using the agar well diffusion method. The micro-dilution method was performed to investigate the minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) in concentrations ranging from 1.95 μg/ml to 500 μg/ml. The evaluation of the antiseptic activity of the Eruca sativa (arugula) seed oil was investigated using time-kill assay in concentrations ranging from 50 μg/ml to 0.195 μg/ml., Results: All tested oils showed variable antimicrobial activities against the tested strains. Arugula, wheat germ, cinnamon, parsley, dill, and onion oils were the most active oils. Among them, arugula oil was the most active oil with MIC 50 and MIC 90 were 3.9 μg/ml and 31.3 μg/ml respectively. MBC 50 and MBC 90 of arugula oil were 15.6 μg/ml and 125μg/ml respectively. The time-kill assay of arugula oil indicated that a concentration of 100 μg/ml completely killed nine of the tested strains after 10 min and reduced the CFU/ml of the rest of the strains by 3 log 10 at the same time interval., Conclusion: Arugula seed oil could be a potentially used as an antiseptic especially for neonates., (© 2022. The Author(s).)

Background: This study assessed the influence of social, economic, and psychological factors on South African's responsiveness to the COVID-19 pandemic. Although the South African government responded quickly to manage the pandemic, the strict lockdown placed a significant burden on the population. Understanding the converging influence of social, economic, and psychological factors on the population's responsiveness is important for improving people's cooperation in controlling COVID-19 and for supporting individuals and communities during the ongoing and future pandemics., Methods: Using data collected from a national telephonic survey (December 2020 to March 2021), we assessed whether selected social, economic and psychological factors were related to: 1) adoption of COVID-19 behavioural measures (hand hygiene, wearing of face masks, and physical distancing), and 2) adherence to government restrictions on movement., Results: South Africans were highly responsive to the pandemic with respondents generally reporting that they very often engaged in the protective behaviours and often to very often adhered to government restriction on movement. However, those from the white population group; with a higher education; living in uncrowded households; who perceived less vulnerability to contracting COVID-19; supported the measures; trusted the scientists; thought the measures by government were implemented fairly and fairly enforced by the police; felt more anxious, sad, hopeless, isolated, angry or had trouble sleeping; inclined to engage in coping behaviour, were more likely to adopt COVID-19 protective behaviours. Furthermore, females, those with a lower education, those less likely to have experienced poverty since the beginning of lockdown; who perceived greater vulnerability to COVID-19, trusted government, and were more supportive of the behavioural measures were more likely to adhere to the restrictions of movement., Conclusions: Strengthening the South African population's responsiveness to the pandemic requires supporting those living in poor socioeconomic circumstances, promoting trust in the scientific evidence, and ensuring that the measures by government are perceived to be fairly implemented and fairly enforced by the police. Due to the impact on livelihoods, restrictions of movement should only be considered if necessary, and this will require trust and confidence in government and strategies to support those experiencing financial hardship., (© 2022. The Author(s).)

While females can suffer serious complications of Fabry disease, most studies are limited to males to avoid confounding by mosaicism. Here, we developed a novel unbiased method for quantifying globotriaosylceramide (GL3) inclusion volume in affected podocytes (F+) in females with Fabry disease independent of mosaicism leading to important new observations. All podocytes in male patients with Fabry are F+. The probability of observing random profiles from F+ podocytes without GL3 inclusions (estimation error) was modeled from electron microscopic studies of 99 glomeruli from 40 treatment-naïve males and this model was applied to 28 treatment-naïve females. Also, podocyte structural parameters were compared in 16 age-matched treatment-naïve males and females with classic Fabry disease and 11 normal individuals. A 4 th degree polynomial equation best described the relationship between podocyte GL3 volume density and the estimation error (R 2  =0.94) and was confirmed by k-fold cross-validation. In females, this model showed that age related directly to F+ podocyte GL3 volume (correlation coefficient (r = 0.54) and podocyte volume (r = 0.48) and inversely to podocyte number density (r = -0.56), (all significant). F+ podocyte GL3 volume was significantly inversely related to podocyte number density (r = -0.79) and directly to proteinuria. There was no difference in F+ podocyte GL3 volume or volume fraction between age-matched males and females. Thus, in females with Fabry disease GL3 accumulation in F+ podocytes progresses with age in association with podocyte loss and proteinuria, and F+ podocyte GL3 accumulation in females with Fabry is similar to males, consistent with insignificant cross-correction between affected and non-affected podocytes. Hence, these findings have important pathophysiological and clinical implications., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Purpose: We sought to investigate the utility of anti-PLA2R antibody as a non-invasive screening method for the diagnosis of primary MN in patients with nephrotic syndrome (NS)., Methods: All consecutive patients with NS admitted in our department, between 01.01.2015 and 31.12.2019 were screened for anti-PLA2R antibodies by an ELISA assay (EUROIMMUN, Lübeck, DE). A positive anti-PLA2R serology was defined as an ELISA value over 2 RU/ml. Subsequently, all patients underwent kidney biopsy to confirm the histological diagnosis., Results: Of the 203 patients with NS, we identified 67 patients with "high" titer of anti-PLA2R antibodies (> 20 RU/ml) and 47 patients with "intermediate" titer (2-20 RU/ml). In the entire cohort, the area under the curve (AUC) was 0.83 (95% CI 0.78-0.89; p < 0.001). With a cutoff of 20 RU/ml, the anti-PLA2R antibodies had a 64% sensitivity (95% CI 53-73%) and 94% specificity (95% CI 88-97%) to discriminate MN from other causes of NS. In addition, the PPV and NPV were 91% (95% CI 82-95%) and 75% (95% CI 69-79%). When analyzing the posttest effect, we identified a LR+ of 11.56 (95% CI 5.2-25.2) and LR- of 0.38 (95% CI 0.29-0.5). The overall accuracy of the test was 80.3% (95% CI 74-85%) and the diagnostic odds ratio was 30.42. When performing subgroup analysis, we identified that in younger patients, in those with preserved renal function or with negative workup for secondary causes, the diagnostic performance of anti-PLA2R antibodies was improved, the sensitivity increasing to 68-71%, the PPV to 93-95% and the LR+ to 12.23-15.4., Conclusion: Serum anti-PLA2R antibody screening in patients with NS is a useful method for the diagnosis of primary MN. In younger patients (less than 60 years old) who have a preserved renal function and a negative workup for secondary causes of NS, a positive anti-PLA2R test highly predicts a diagnosis of primary MN., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Renal involvement is a frequent complication of systemic lupus erythematosus (SLE). It occurs in up to two-thirds of patients, often early during the disease course, and is the most important predictor of the morbidity and mortality of SLE patients. Despite tremendous improvements in the approach of the lupus nephritis (LN) therapy, including the recent approval of two new disease-modifying therapies, up to 50% of patients do not obtain a renal response and up to 25% will eventually progress to end-stage renal disease (ESRD) within 10 years of diagnosis. Given the lack of correlation between clinical features and histological lesions, there is an increasing need for a histology-guided approach to the management of patients with LN. Apart from the initial diagnosis of type and severity of renal injury in SLE, the concept of a repeat kidney biopsy (either in a for-cause or a per-protocol scenario) has begun to gain increasing popularity in the nephrology community. Herein, we will provide a comprehensive overview of the most important areas of utility of the kidney biopsy in patients with LN.

Rationale: Since mass-scale severe acute respiratory syndrome coronavirus 2 vaccination, there have been case reports of several immune-mediated reactions, including new-onset and flares of glomerular disorders following immunization with mRNA coronavirus disease 2019 vaccines. Here, we report two cases, the first to our knowledge, of relapsing cryoglobulinemic vasculitis with new-onset severe renal involvement following mRNA coronavirus disease 2019 vaccination., Patient Concerns: The relapse of the cutaneous and the new onset of severe renal involvement of cryoglobulinemic vasculitis occurred three weeks after the second dose of the mRNA Moderna coronavirus disease 2019 vaccination and two days after the first dose of mRNA Pfizer coronavirus disease 2019 vaccination in the first and second patient, respectively., Diagnosis: Kidney biopsies were performed. The first pacient's kidney biopsy showed a membranoproliferative pattern of glomerular injury with extensive mesangial and endocapillary hypercellularity, while severe endothelial swelling, loss of fenestrations and widening of subendothelial space were identified by electron-microscopy. The second patient's kidney biopsy was consistent with cryoglobulin associated membrano-proliferative pattern of glomerular injury., Interventions: Our patients were managed with a combination of immunosuppressants consisting of corticosteroids, Cyclophosphamide and Rituximab with a favourable outcome at the end of the induction period., Outcomes: Clinical and immunological response was achieved in both patients after four months of follow-up., Lessons: The temporal association of the relapse of the cryoglobulinemic vasculitis to mRNA coronavirus disease 2019 vaccination suggest that the vaccine might have been a trigger for the reactivation of the disease in our cases. This possible association should be acknowledged by physicians in order to provide optimal monitoring and treatment in case of reactivation of the disease post-immunization., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Several SARS-CoV-2 variants with increased transmissibility and/or potential immune escape have emerged and rapidly spread worldwide. Ongoing surveillance analyses are performed worldwide to designate new variants of concern (VOC) of coronavirus., Main Text: This report identifies the first Egyptian patient with a confirmed SARS-CoV-2 omicron variant. The patient showed positivity on reverse transcriptase-polymerase chain reaction and full genome sequencing was performed to confirm the variant. The mutations found in the variant were compared with the GISAID reference strain hCoV-19/Wuhan/WIV04/2019. Genome BLAST showed the highest similarity to omicron variants isolated in South Africa. Phylogenetic analysis revealed that the variant belongs to the 21K clade., Conclusions: The study indicates the importance of information-sharing among global public health partners. Moreover the importance of implementation of full genome sequencing to rapidly identify and track the new SARS-CoV-2 variants., (© 2022. The Author(s).)

Background: Identifying patients with BRCA mutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming., Methods: The Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer., Results: Oncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1 or BRCA2, and there was no difference between psychosocial measures for carriers in both arms., Conclusion: The MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Violence among youth is a major health and safety burden globally. There is a dearth in the development and evaluation of targeted interventions that addresses the multi-faceted nature of youth violence to ensure effectiveness and replicability. This study aims to systematically evaluate the fidelity of implementation of the Building Bridges Mentoring intervention that focuses on the prevention of youth violence in two low-income communities in South Africa. This study employed a mixed methods concurrent triangulation design. Qualitative data were analysed using deductive thematic analysis, and quantitative data using descriptive statistics and T -tests. The results indicate that for all the intervention components, implementation fidelity (i.e. adherence, exposure, quality of programme delivery, and participant responsiveness) was generally moderate to high, suggesting a 'good' implementation of the programme in the real world. Evaluating the fidelity of implementation is vital to obtain a comprehensive insight into whether an intervention was implemented according to its design, and to verify and validate the findings and outcomes, and accord credibility and integrity of the study.

Background: Although automated urine cultures (UCs) following urinalysis (UA) are often used in emergency departments (EDs) to identify urinary tract infections (UTIs), results are often reported as no organism growth or the growth of clinically insignificant organisms, leading to the overdetection and overtreatment of asymptomatic bacteriuria (ASB)., Methods: A process change was implemented at a US Department of Veterans Affairs medical center ED that automatically cancelled UCs if UAs had < 5 white blood cells per high-power field (WBC/HPF). An option for do not cancel (DNC) UC was available. Data were prospectively collected for 3 months postimplementation and included UA/UC results, presence of UTI symptoms, antibiotics prescribed, and health care utilization., Results: Postintervention, 684 UAs (37.2%) were evaluated from ED visits. Postintervention, of 255 UAs, 95 (37.3%) were negative with UC cancelled, 95 (37.3%) were positive with UC processed, 43 (16.9%) were ordered as DNC, and 22 (8.6%) were ordered without a UC. UC processing despite a negative UA significantly decreased from 100% preintervention to 38.6% postintervention ( P < .001). Inappropriate prescribing of antibiotics for ASB was reduced from 10.2% preintervention to 1.9% postintervention (odds ratio = 0.17; P = .01). In patients with negative UA specimens, antibiotic prescribing decreased by 25.3% postintervention. No reports of outpatient, ED, or hospital visits for symptomatic UTI were found within 7 days of the initial UA postintervention., Conclusions: The UA to reflex culture process change resulted in a significant reduction in processing of inappropriate UCs and unnecessary antibiotic use for ASB. There were no missed UTIs or other adverse patient outcomes., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article., (Copyright © 2022 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

We sought to evaluate the association between de novo donor-specific antibodies (dnDSAs) class and their mean fluorescence intensity (MFI) with donor-derived cell-free DNA (dd-cfDNA), aiming to further clarify the biomarker utility of these noninvasive tests in relation to renal allograft function and histology., Methods: The study included kidney transplant recipients (n = 171) who underwent surveillance testing with DSA and dd-cfDNA as part of their clinical care between September 2017 and December 2019 at our center., Results: We identified dnDSA in 43 patients (25%) at a median of 4.63 y (IQR, 1.5-7) posttransplant. The presence of DSA with MFI >2500 was associated with a median dd-cfDNA of 0.96% (IQR, 0.26-2.95) significantly higher than in patients with DSA MFI <2500 (0.28%; IQR, 0.19-0.39) or without detectable DSA (0.22%; IQR, 0.17-0.37; P < 0.001). Class II dnDSAs were the most prevalent dnDSA (88.3%), the majority with MFI >2500 (82.9%). Patients with DQ-dnDSAs (47.4%) had higher MFI and dd-cfDNA levels than other class II dnDSAs. By comparison, all patients that developed only class I DSAs had MFI <2500 and a low dd-cfDNA. In addition, the serum creatinine was 1.55 ± 0.48 mg/dL in those dnDSA-negative, 1.15 ± 0.37 mg/dL in those with dnDSA MFI <2500, and 1.53 ± 0.66 mg/dL in those with dnDSA MFI >2500 ( P = 0.05). After multivariate adjustment, an elevated dd-cfDNA was independently associated with the presence of dnDSA with MFI ≥2500. We identified that both dd-cfDNA and dnDSAs were strongly associated with antibody-mediated rejection, whereas for individual Banff histological lesions, DSA MFIs ≥2500 had the strongest association with C4d staining score and dd-cfDNA >1% with microvascular inflammation., Conclusions: Our study identifies class II dnDSA as being strongly associated with late alloimmune injury post kidney transplant independent of allograft dysfunction and shows that dd-cfDNA may complement the clinical significance of dnDSAs., Competing Interests: N.L. received institution level funding from CareDx, Natera, Novartis, TGI, Angion, and BMS. The remaining authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)