Multi-organ Impairment Research Articles

Dichlorvos evokes systemic lipid dysmetabolism in Wistar rats: rescindment influence of curcumin

Organophosphorus pesticides such as dichlorvos (DDVP) are often employed to eradicate pests, especially in low and medium-income countries. However, they have several negative impacts on the visceral organs. Astonishingly, curcumin protects organs from the detrimental effects of xenobiotics via the maintenance of redox homeostasis; unfortunately, its role in dichlorvos-provoked multi-organ impairment vis-à-vis lipid homeostasis has not been examined. Therefore, this undertaking probed the remedial efficacy of curcumin on DDVP-prompted combined systemic toxicity and major lipid distribution. Randomization was engaged to dedicate rats (40) into seven groups (6 rats/group): control, DDVP only (20 mg kg-1day-1), DDVP administered with either curcumin (50 and 100 mg kg-1day-1) or reference medication atropine (0.2 mg kg-1day-1), and curcumin only (50 and 100 mg kg-1day-1). DDVP was dispensed orally for one week, followed by two weeks of curcumin treatment. Twenty-four hours after the last administration, we sacrificed the rats and collected their blood and viscera (liver, kidney, heart, lung, and brain) for bioassays. Curcumin remarkably (p<0.05) rescinded DDVP-mediated increases in plasma, LDL, and systemic cholesterol; markedly (p<0.05) attenuated DDVP-elicited decreases in HDL-cholesterol and TAG contents in all the compartments except erythrocyte and liver; and significantly (p<0.05) abated DDVP-induced plasma phospholipidaemia, multi-organ phospholipidosis, and up-regulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA-R) activity. This finding demonstrated that curcumin reverses DDVP-triggered anomalous lipid dynamics by abating cholesterogenesis and phospholipidosis and restoring HMG-CoA-R activity.

THE GLA D313Y MUTATION IN FABRY DISEASE: DIAGNOSTIC DILEMMAS AND THERAPEUTIC CONSIDERATIONS

Abstract Fabry disease is a genetic disorder caused by mutations in the GLA gene, which encodes alpha–galactosidase A, leading to enzyme dysfunction and subsequent accumulation of glycosphingolipids. In the classical form, it occurs in childhood or early adolescence with renal, cardiac, and neurological involvement, resulting in a poor prognosis. The GLA D313Y is a missense mutation resulting in a significant reduction of enzyme activity in plasma, while leukocyte enzyme activity remains within normal limits, leading to a "pseudo–deficiency" of enzyme activity with uncertain pathogenicity. In literature, it has been observed that individuals with this mutation may present predominantly with central neurologic manifestations, characterized by multifocal white matter lesions. Historically they do not receive indications for initiating enzyme replacement or molecular chaperone therapies. We present the case of a man affected by arterial hypertension and history of chronic lower limb pain who experienced a lacunar stroke at the age of 35. The GLA D313Y mutation was identified and enzyme activity assay in plasma was within normal limits, precluding the initiation of enzyme replacement therapy. Over the following years, he suffered two additional ischemic strokes, a progressive decline in renal function to stage 3, and acute coronary syndrome. Transthoracic echocardiography revealed hypertrophic non–obstructive cardiomyopathy (SIVd 20 mm) with normal biventricular ejection fraction. Cardiac magnetic resonance showed late gadolinium enhancement of inferior junctional and inferior wall in middle segment (Fig.1). Considering the patient‘s clinical conditions involving multi–organ impairment, an enzymatic activity test was performed on leukocytes, revealing a reduced activity. This prompted the decision to initiate enzyme replacement therapy. This case report supports the hypothesis that the D313Y mutation may be associated with a later presentation and not only neurological involvement. In our experience, it’s mandatory to proceed with the determination of leukocyte enzyme activity in presence of normal enzyme activity in plasma. As an alternative, the detection of glycosphingolipids’ accumulation could be useful, but myocardial and renal biopsy poses a high bleeding risk, especially in anticoagulated or antiaggregated patients. The authors propose considering the initiation of therapy in patients with the D313Y mutation who exhibit significant organ involvement.

Atypical Influx: Navigating Invasive Group A Streptococcus Cases in Emergency General Surgery

Abstract Aim To highlight the rising national incidence of iGAS infections, particularly during the post emergency phase of the COVID-19 pandemic, and emphasise its significance as a differential diagnosis in acutely unwell emergency surgical patients. Methods Data was gathered retrospectively from December 2022 - August 2023. Inclusion criteria were emergency surgical patients testing positive for GAS isolated from sterile sites, or non-sterile sites in case of septic shock. Results Six cases (four females, two males), with a mean age of 55 (36-67) were identified. Four had necrotizing fasciitis, one bacterial peritonitis in the presence of a ventriculo-peritoneal shunt, and one streptococcal bacteremia. All presented in septic shock, with metabolic acidosis and multiorgan impairment. The initial diagnosis was clinical in 66% of cases. iGAS was confirmed via wound, peritoneal fluid, tissue or blood culture in five patients and via genital swab in one. 50% of cases were sensitive to clindamycin and amoxicillin. Two received IV immunoglobulins. All cases were managed according to Sepsis 6 protocols, involving multidisciplinary teams. Five patients underwent immediate surgery for debridement and washout. The mortality rate was 16.6%. Three patients were transferred to tertiary centres once stabilised (1 for neurosurgical input, and 2 for plastics grafting). Conclusion It is crucial for frontline doctors to consider iGAS as a differential when encountering critically ill surgical patients. Simultaneous systemic resuscitation, early surgical intervention, multidisciplinary care, tailored antibiotic therapy and immunoglobulins are essential to minimise morbidity and mortality.

Obesity and COVID-19 Pandemics: Epidemiology, Mechanisms, and Management.

Obesity is a principle causative factor of various metabolic dysfunctions, chronic inflammation, and multi-organ impairment. The global epidemic of obesity has constituted the greatest threat to global health. Emerging evidence has associated obesity with an increased risk of severe infection and poor outcomes from coronavirus disease 2019 (COVID-19). During current COVID-19 pandemic, the interaction between COVID-19 and obesity has exaggerated the disease burden of obesity more than ever before. Thus, there is an urgent need for consideration of universal measures to reduce the risk of complications and severe illness from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in obesity population. In this review, we first summarized the clinical evidence on the effect of obesity on susceptibility, severity, and prognosis of COVID-19. Then we discussed and the underlying mechanisms, including respiratory pathophysiology of obesity, dysregulated inflammation, upregulated angiotensin-converting enzyme 2 (ACE2) expression, hyperglycemia, and adipokines. Finally, we proposed recommendations on how to reduce the spread and pandemic of SARS-CoV-2 infection by prevention and treatment of obesity.

Antioxidant, anti-inflammatory and antiseptic molecular actions of gedunin against lipopolysaccharide-induced sepsis in experimental rats.

Sepsis is a life-threatening organ dysfunction without effective therapeutic options. Lipopolysaccharide (LPS), a bacterial endotoxin, is known to induce sepsis. It is associated with oxidative stress, inflammation and multiple organ failure. Gedunin (GN) is a tetranortriterpenoid isolated from the Meliaceae family. Gedunin possesses numerous pharmacological properties, including antibacterial, anti-inflammatory, antiallergic, and anticancer activities. However, the molecular anti-inflammatory mechanism of GN in sepsis has not been established. The aim of the study was to explore the antioxidant and anti-inflammatory molecular actions underlying the antiseptic activity of GN in an LPS-induced rat model. Rats were randomized into 4 sets: group 1 (control) was given 1 mL of dimethyl sulfoxide (DMSO) by gavage, group 2 rats were treated with LPS (100 μg/kg body weight (BW), intraperitoneally (ip.)), group 3 rats were given LPS (100 μg/kg BW, ip.)+GN (50 mg/kg BW in DMSO), and rats in the group 4 were given GN (50 mg/kg BW in DMSO) alone. We studied hepatic markers, inflammatory cytokines and antioxidants using specific biochemical kits and analyzed their statistical significance. Histopathology of liver, lungs and kidney tissues was also explored. The mRNA levels and conducted protein investigations were performed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, respectively. Our findings revealed that GN significantly (p < 0.05) inhibited oxidative stress, lipid peroxides, toxic markers, pro-inflammatory cytokines, and histological changes, thereby preventing multi-organ impairment. Additionally, GN attenuated the HMGβ1/NLRP3/NF-κB signaling pathway and prevented the degradation of Iκβα. Gedunin is a promising natural antiseptic agent for LPS-induced sepsis in rats.

Association between Aspartate Aminotransferase to Platelet Ratio Index with Sepsis-Associated Liver Injury and Outcome in Children

BACKGROUND: Sepsis-associated liver injury (SALI) is among the major clinical characteristics of pediatric septicemia, and it is a distinct risk factor for multiorgan impairment and a high rate of death. The prompt identification and treatment of SALI in patients with septic conditions is critical. AIM: We aimed to discover the relationship between aspartate aminotransferase to platelet ratio index (APRI) and Sepsis-associated liver injury (SALI) as an early predictor. METHODS: Analytical observational study with a prospective cohort approach with primary data taken from 49 samples. Further, these results were analyzed to determine the relationship between the occurrence of SALI and laboratory results. RESULTS: The results of the analysis conducted from 49 samples, 23 people (46.9%) had SALI, and 22 people (44.9%) died. The median length of stay in the pediatric intensive care unit (PICU) was 9 days (interquartile range = 6.5–12.5). Significant relationship between aspartate aminotransferase to platelet ratio index (APRI) and the incidence of SALI with odds ratio (95% confidence interval) 2.32 (1.21: 4.44) and p = 0.011. The higher the APRI value, the longer the stay in the PICU. The correlation value (r) is 0.348 or low correlation CONCLUSION: There was a significant relationship between the APRI and sepsis-related liver injury as well as sepsis outcomes such as PICU length of stay and mortality. Increases in the APRI increase the risk of sepsis-related liver injury, mortality, and PICU length of stay.

In their own words: Safety and quality perspectives from families of hospitalized children with medical complexity.

Children with medical complexity (CMC) experience adverse events due to multiorgan impairment, frequent hospitalizations, subspecialty care, and dependence on multiple medications/equipment. Their families are well-versed in care and can help identify safety/quality gaps to inform improvements. Although previous studies have shown families identify important safety/quality gaps in hospitals, studies of inpatient safety/quality experience of CMC and their families are limited. To address this gap and identify otherwise unrecognized, family-prioritized areas for improving safety/quality of CMC, we conducted a secondary qualitative analysis of safety reporting surveys among families of CMC. Explore safety reports from families of hospitalized CMC to identify areas to improve safety/quality. We analyzed free-text responses from predischarge safety reporting surveys administered to families of CMC at a quaternary children's hospital from April 2018 to November 2020. Using a qualitative descriptive approach, we categorized responses into standard clinical categories. Three team members inductively generated an initial codebook to apply iteratively to responses. Reviewers coded responses collaboratively, resolved discrepancies through consensus, and generated themes. Outcomes: family-reported areas of safety/quality improvement. pre-discharge family surveys. Two hundred and eight/two hundred and thirty-seven (88%) families completed surveys; 83 families offered 138 free-text safety responses about medications, feeds, cares, and other categories. Themes included unmet expectations of hospital care/environment, lack of consistency, provider-patient communication lapses, families' expertise about care, and the value of transparency. To improve care of CMC and their families, hospitals can manage expectations about hospital limitations, improve consistency of care/communication, acknowledge family expertise, and recognize that family-observed quality concerns can have safety implications. Soliciting family input can help hospitals improve care in meaningful, otherwise unrecognized ways.

Experience in the diagnosis and treatment of pneumonia caused by infection with Tropheryma whipplei: A case series

Tropheryma whipplei (TW) is the root cause of Whipple’s disease (WD), a rare infectious illness leading to multi-organ impairment. A prominent feature of WD is acute pneumonia, which can be exceedingly challenging to diagnose clinically due to the pathogen’s surreptitious nature. However and significantly, with the advent of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF), it offers clinicians a potent tool at their disposal to detect TW infections. The present study conducted a retrospective analysis of clinical data gleaned from five patients in Hunan Province in China. Findings in this study demonstrated the potential of BALF-mNGS in diagnosing pneumonia caused by TW infection.

Prevalence rates of mucopolysaccharidosis in Iraq: a retrospective cross-sectional observational study

Background: Mucopolysaccharidosis (MPS) is a rare hereditary inborn error of metabolism that represents the largest heterogeneous group of lysosomal storage diseases (LSD) and is characterized by multiorgan impairment due to glycosaminoglycans (GAGs) accumulation in various tissues and organs, resulting in severe frailty and early death. This research aimed to figure out the specific and overall birth prevalence of mucopolysaccharidosis among Iraqi children, as well as the frequencies of each type, and to compare the results with epidemiological data from other Arabian countries. Methods: Information was collected and investigated from registered patients diagnosed with MPS in five metabolic centers in Iraq between 2010 and 2020. The numbers of live births in Iraq were obtained from the Ministry of Health and Environment (Health and vital statistics department) for the period mentioned above. Birth prevalence was calculated, and Poisson distribution for confidence intervals (95%) was considered through the implementation of MedCalc statistical software. The Hardy-Weinberg equation was used to calculate carrier frequency. Results: The overall prevalence of MPS at birth is 2.97 per 100,000 live births; different forms of MPS manifest at varied frequencies. MPS VI was the most often reported form in the Iraqi population (1.32 per 100,000 live births, or 44.41% of all MPS cases), followed by MPS IVA and MPS I (0.625 and 0.593 per 100,000 live births, respectively). The higher frequency rate of MPS VI was also reported in neighboring countries, including UAE and Saudi Arabia, which were 2.51 and 8.0 per 100,000 live births, respectively. Conclusions: The health systems should highly consider data obtained from prevalence studies in all affected countries, including health care specialists, clinical genetics, and workers in laboratories involved in MPS diagnosis.

Infection Induced Fetal Inflammatory Response Syndrome (FIRS): State-of- the-Art and Medico-Legal Implications-A Narrative Review.

Fetal inflammatory response syndrome (FIRS) represents the fetal inflammatory reaction to intrauterine infection or injury, potentially leading to multiorgan impairment, neonatal mortality, and morbidity. Infections induce FIRS after chorioamnionitis (CA), defined as acute maternal inflammatory response to amniotic fluid infection, acute funisitis and chorionic vasculitis. FIRS involves many molecules, i.e., cytokines and/or chemokines, able to directly or indirectly damage fetal organs. Therefore, due to FIRS being a condition with a complex etiopathogenesis and multiple organ dysfunction, especially brain injury, medical liability is frequently claimed. In medical malpractice, reconstruction of the pathological pathways is paramount. However, in cases of FIRS, ideal medical conduct is hard to delineate, due to uncertainty in diagnosis, treatment, and prognosis of this highly complex condition. This narrative review revises the current knowledge of FIRS caused by infections, maternal and neonatal diagnosis and treatments, the main consequences of the disease and their prognoses, and discusses the medico-legal implications.

Multi-organ impairment and long COVID: a 1-year prospective, longitudinal cohort study.

To determine the prevalence of organ impairment in long COVID patients at 6 and 12 months after initial symptoms and to explore links to clinical presentation. Prospective cohort study. Individuals. In individuals recovered from acute COVID-19, we assessed symptoms, health status, and multi-organ tissue characterisation and function. Two non-acute healthcare settings (Oxford and London). Physiological and biochemical investigations were performed at baseline on all individuals, and those with organ impairment were reassessed. Primary outcome was prevalence of single- and multi-organ impairment at 6 and 12 months post COVID-19. A total of 536 individuals (mean age 45 years, 73% female, 89% white, 32% healthcare workers, 13% acute COVID-19 hospitalisation) completed baseline assessment (median: 6 months post COVID-19); 331 (62%) with organ impairment or incidental findings had follow-up, with reduced symptom burden from baseline (median number of symptoms 10 and 3, at 6 and 12 months, respectively). Extreme breathlessness (38% and 30%), cognitive dysfunction (48% and 38%) and poor health-related quality of life (EQ-5D-5L < 0.7; 57% and 45%) were common at 6 and 12 months, and associated with female gender, younger age and single-organ impairment. Single- and multi-organ impairment were present in 69% and 23% at baseline, persisting in 59% and 27% at follow-up, respectively. Organ impairment persisted in 59% of 331 individuals followed up at 1 year post COVID-19, with implications for symptoms, quality of life and longer-term health, signalling the need for prevention and integrated care of long COVID.Trial Registration: ClinicalTrials.gov Identifier: NCT04369807.

Host Response of Syrian Hamster to SARS-CoV-2 Infection including Differences with Humans and between Sexes.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the importance of having proper tools and models to study the pathophysiology of emerging infectious diseases to test therapeutic protocols, assess changes in viral phenotypes, and evaluate the effects of viral evolution. This study provided a comprehensive characterization of the Syrian hamster (Mesocricetus auratus) as an animal model for SARS-CoV-2 infection using different approaches (description of clinical signs, viral load, receptor profiling, and host immune response) and targeting four different organs (lungs, intestine, brain, and PBMCs). Our data showed that both male and female hamsters were susceptible to the infection and developed a disease similar to the one observed in patients with COVID-19 that included moderate to severe pulmonary lesions, inflammation, and recruitment of the immune system in the lungs and at the systemic level. However, all animals recovered within 14 days without developing the severe pathology seen in humans, and none of them died. We found faint evidence for intestinal and neurological tropism associated with the absence of lesions and a minimal host response in intestines and brains, which highlighted another crucial difference with the multiorgan impairment of severe COVID-19. When comparing male and female hamsters, we observed that males sustained higher viral RNA shedding and replication in the lungs, suffered from more severe symptoms and histopathological lesions, and triggered higher pulmonary inflammation. Overall, these data confirmed the Syrian hamster as a suitable model for mild to moderate COVID-19 and reflected sex-related differences in the response against the virus observed in humans.

Six-month multidisciplinary follow-up in multisystem inflammatory syndrome in children: An Italian single-center experience.

A severe multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 has been described after infection. A limited number of reports have analyzed the long-term complications related to pro-inflammatory status in MIS-C. We evaluated multiorgan impairment at the 6-month follow-up in MIS-C. We enrolled 33 pediatric patients consecutively hospitalized for MIS-C and monitored for almost 6 months. The inter-relationship of patient's features and disease severity at admission with long term complications was studied by multivariate analysis. Endo-metabolic derangement, cardiac injury, respiratory, renal and gastrointestinal manifestations and neurological involvement are part of the initial presentation. The most abnormalities appear to resolve within the first few weeks, without significant long term dysfunction at the 6-months follow-up, except for endocrine (non-thyroidal illness syndrome in 12.1%, insulin resistance in 21.2%) and neurological system (27.3% cognitive or psychological, behavioral, adaptive difficulties). Endocrine and heart involvement at admission represent a significant factor on the long term sequelae; however no association between severity score and long-term outcome was noted. The severity of initial clinical presentation may be associated to organ domain, however it is not related to long term sequelae. The prevalent organ restoration supports a predominant indirect immune-mediated injury triggered by a systemic inflammatory response; however a direct damage due to the viral entry could be not excluded. Eventhought our preliminary results seem to suggest that MIS-C is not a long-term risk condition for children health, a longer follow-up is mandatory to confirm this hypothesis.

Povezanost polimorfizama glutation S-transferaza sa biomarkerima inflamacije i multiorganskog oštećenja u COVID-19

Introduction: Due to the established role of oxidative stress in the pathophysiology of COVID-19, it has been proposed that inter-individual differences in patients' clinical manifestations might be affected by variations in genes encoding antioxidant enzymes, such as glutathione S-transferases (GSTs). Aim: The aim of this study was to assess the association of polymorphisms in cytosolic GSTs (GSTA1 rs3957357, GSTM3 rs1332018 and GSTP1 rs1695) with inflammatory parameters (leukocytes, lymphocytes, monocytes, C-reactive protein (CRP), fibrinogen, ferritin) and multiorgan impairment biomarkers (urea, creatinine, AST, ALT, LDH) in COVID-19 patients at two-time points. Material and methods: GSTM3, GSTA1 and GSTP1 genotypes were determined in 150 COVID-19 patients by appropriate polymerase chain reaction (PCR) methods. Results: Inflammatory biomarkers (leukocytes, lymphocytes, monocytes) increased 7 days upon admission to the hospital (p &lt; 0.001), while CRP and fibrinogen decreased (p &lt; 0.001). Out of five analyzed multiorgan impairment biomarkers, only urea increased significantly 7 days upon admission (p &lt; 0.007), while AST showed a statistically significant drop (p &lt; 0.001). COVID-19 patients homozygous for variant GSTM3*C/C genotype had increased levels of inflammatory biomarkers such as CRP, fibrinogen and ferritin, but the borderline significance was observed only for fibrinogen (p = 0.057). COVID-19 patients homozygous for variant GSTM3*C allele had the highest levels of ALT (p = 0.021) and LDH (p = 0.045) upon admission. Conclusion: Our results on the association between GSTM3 variant genotype with parameters of systemic inflammation and liver damage in COVID-19 patients can contribute to further understanding of pathophysiological mechanisms underpinning this disease, as well as early recognition of COVID-19 patients prone to worse course of the disease.

Bardet–Biedl Syndrome: A Brief Overview on Clinics and Genetics

AbstractBardet–Biedl syndrome is a genetically pleiotropic disorder characterized by high clinical heterogeneity with severe multiorgan impairment. Clinically, it encompasses primary and secondary manifestations, mainly including retinal dystrophy, mental retardation, obesity, polydactyly, hypogonadism in male, and renal abnormalities. At least 21 different genes have been identified, all involved into primary cilium structure or function. To date, genotype–phenotype correlation is still poor.

Quantitative MRI Detects Multi-Organ Impairment in Patients with Chronic Myeloid Neoplasms

Quantitative MRI Detects Multi-Organ Impairment in Patients with Chronic Myeloid Neoplasms

Challenges in Managing Melioidosis with Fulminant Sepsis: A Case Report

Managing melioidosis with fulminant sepsis is difficult and challenging. We describe the case of a 30-year-old man with clinical presentation of non-specific septicemic shock with multi organ impairment and severe respiratory distress. The causative organism, Burkholderia pseudomallei was only identified on day 4 of ICU admission. Imaging investigation revealed multiple lung and splenic abscesses. This led to delay in the diagnosis and initiating specific antimicrobial therapy which arise from difficulties in clinical recognition and laboratory diagnosis. Our patient was managed in the ICU for 23 days with intensive antimicrobial therapy. As for now, we should increase the awareness of melioidosis in treating our patients and realize its burden to our community and hoping that a better diagnostic test will arise and helps us in achieving early confirmatory diagnosis and guide for better therapeutic efficacy and survival of the patients.

Hematological profile of COVID-19 patients in Ramanagar district, Karnataka - A cross sectional study

Introduction and Aim: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which rapidly evolved into a pandemic infecting humans all over the world. Whether hematologic and immunologic responses play a crucial role in progression of COVID-19 is still not clear. Increasing scientific evidence has shown that abnormalities in routine hematological tests, have the potential to diagnose SARS-CoV-2 infection in an economical way. Major laboratory changes indicating systemic inflammation and multi-organ impairment including hematopoietic system leading to lymphocytopenia, neutrophilia, eosinopenia, mild thrombocytopenia and ratios derived from these hematological parameters indicated severe disease and/or fatal outcomes. The aim was to study the hematological profile of Covid-19 patients admitted at a tertiary care hospital at Ramanagar district. Materials and Methods: This retrospective study included 260 confirmed cases of Covid-19 diagnosed at a tertiary health care centre. Demographic, clinical, laboratory, treatment, and outcome data were extracted from the institutional electronic medical records after obtaining permission from the concerned authorities. From CBC test results obtained neutrophil lymphocyte ratio was derived. Results: The present study revealed that majority of Covid positive patients presented with lymphopenia. While a significant association was observed between N/L ratio and disease severity, no significant association was seen between platelet count and severity of the disease. Conclusion: Since the results of the present study features lymphopenia among large proportion of patients and elevated N/L ratio among critically ill patients these markers could be utilized as useful prognostic indicators during the initial assessment of disease severity and thus appropriate management can be planned for such patients before the condition of the patient deteriorates.

Early Renal-Replacement Therapy May Reduce the All-Cause Mortality of Severe COVID-19: An Observational Cohort Study

Introduction: The efficacy of renal-replacement treatment (RRT) remains to be validated in COVID-19. In this retrospective cohort study, we aimed to assess the efficacy of early initiation of RRT in intensive care unit (ICU) adults with severe COVID-19. Methods: Fifty-eight adult patients in ICU with critically ill or severe COVID-19 with a tendency of critical illness were recruited from February 9, 2020, to March 30, 2020. Early RRT were determined by the ICU medical team based on boom in cytokines levels, increased organs injury/failure, and rapid aggravation of condition. All participants were followed up from the first day of ICU admission to March 30, 2020. The primary outcome was all-cause mortality in ICU. Results: The mean age of the cohort was 68.4 ± 14.6 years, with 81.0% having at least one comorbidity before hospitalization. Twenty patients (34.5%) initiated early RRT after 24.1 ± 10.4 days from the onset and 6.4 ± 3.6 days from ICU admission. Thirty-four of 58 participants (58.6%) died during ICU follow-up. Univariate and multivariate Cox proportional-hazards model showed that early RRT was associated with a lower risk of all-cause mortality in ICU with an adjusted HR of 0.280 (95% CI: 0.106–0.738, p = 0.010). Sudden unexpected death (SUD) was remarkably reduced in the early RRT group, compared with the control group (0.2 vs. 2.9 per 100 person-day, p = 0.02). Conclusion: Early RRT can reduce the all-cause in-hospital mortality, especially SUD in patients with severe COVID-19, but not improve multi-organ impairment or increase the risk of AKI. Early initiation of RRT merits an optional strategy in critically ill patients with COVID-19 (ChiCTR2000030773).

Fabry's Disease: The Utility of a Multidisciplinary Screening Approach.

(1) Background: As a lysosomal storage disorder, Fabry’s disease (FD) shows variable clinical manifestations. We applied our multidisciplinary approach to identify any organ damage in a sample of adult patients with different pathogenic variants. (2) Methods: 49 participants (mean age 44.3 ± 14.2 years; 37 females), underwent a multidimensional clinical and instrumental assessment. (3) Results: At diagnosis, mean enzymatic activity was 5.2 ± 4.6 nM/mL/h in females and 1.4 ± 0.5 nM/mL/h in males (normal values > 3.0), whereas globotriaosylsphingosine was 2.3 ± 2.1 nM/L in females and 28.7 ± 3.5 nM/L in males (normal values < 2.0). Overall, cardiovascular, neurological, and audiological systems were the most involved, regardless of the variant detected. Patients with classic variants (10) showed typical multiorgan involvement and, in some cases, prevalent organ damage (cardiovascular, neurological, renal, and ocular). Those with late-onset variants (39) exhibited lower occurrence of multiorgan impairment, although some of them affected the cardiovascular and neurological systems more. In patients with lower enzymatic activity, the most frequent involvement was neurological, followed by peripheral vascular disease. (4) Conclusions: FD patients exhibited wide phenotypic variability, even at single-organ level, likely due to the individual genetic mutation, although other factors may contribute. Compared to the conventional management, a multidisciplinary approach, as that prompted at our Center, allows one to achieve early clinical detection and management.