Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

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Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

/pdf/extrapulmonary-manifestations-of-covid-19-5gbdx3z1ea.pdf

Extrapulmonary manifestations of COVID-19.

To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.

https://link.springer.com/content/pdf/10.1007/s00405-020-05965-1.pdf

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.

To investigate safety, feasibility, and effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of COVID-19 patients with persistent olfactory dysfunction (OD). From March 2022 to July 2022, COVID-19 patients with persistent OD were consecutively recruited to benefit from PRP injection into the olfactory clefts. Patient pain, annoyance, time of procedure, and adverse events were evaluated. Olfactory function was evaluated at baseline and 2-month post-injection with the olfactory disorder questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test. Eighty-seven patients with anosmia (N = 30), hyposmia (N = 40), or parosmia (N = 17) with a mean OD duration of 15.7 months completed the evaluations. The PRP injection was successfully performed in all patients with a mean procedure time of 18.4 ± 3.4 min. The adverse events included transient epistaxis (N = 31), parosmia related to xylocaine spray (N = 10), and vasovagal episode (N = 2). The injection procedure was evaluated as somewhat or moderately painful by 41 (47%) and 22 (25%) patients, respectively. Thirty-seven patients were assessed after 2 months post-injection. The mean ODQ and TDI scores significantly improved from baseline to 2-month post-injection (p < 0.01). The olfactory improvement occurred after a mean of 3.6 ± 1.9 weeks. The injection of PRP into the olfactory clefts is safe and associated with adequate patient-reported outcomes. The findings of this preliminary study suggest possible efficacy on subjective and psychophysical evaluations, but future randomized controlled studies are needed to determine the superiority of PRP injection over placebo. 

https://link.springer.com/content/pdf/10.1007/s00405-022-07788-8.pdf

Platelet-rich plasma injection in the olfactory clefts of COVID-19 patients with long-term olfactory dysfunction

Proton pump inhibitors (PPIs) are commonly prescribed for laryngopharyngeal reflux (LPR), but their efficacy remains debated. Alginates is an option for the treatment of LPR with few adverse effects. The study aimed to investigate the non-inferiority of an alginate suspension (Gastrotuss®) compared to PPIs (Omeprazole) in reducing LPR symptoms and signs.A non-inferiority randomized controlled trial was conducted. Fifty patients with laryngopharyngeal symptoms (Reflux Symptom Index -RSI- ≥ 13) and signs (Reflux Finding Score -RFS- ≥ 7) were randomized in two treatment groups: (A) Gastrotuss® (20 ml, three daily doses) and, (B) Omeprazole (20 mg, once daily). The RSI and the RFS were assessed at baseline and after 2 months of treatment.Groups had similar RSI and RFS scores at baseline. From pre- to 2-month posttreatment, the mean RSI significantly decreased (p = 0.001) in alginate and PPI group (p = 0.003). The difference between groups in the RSI change was not significant (95%CI: - 4.2-6.7, p = 0.639). The mean RFS significantly decreased in alginate (p = 0.006) and PPI groups (p = 0.006). The difference between groups in the mean change RFS was not significant (95%CI: - 0.8; 1.4, p = 0.608).After 2 months of treatment, LPR symptoms and signs are significantly reduced irrespective of the treatment. Alginate was non-inferior to PPIs and may represent an alternative treatment to PPIs for the treatment of LPR. 

https://link.springer.com/content/pdf/10.1007/s00405-021-07219-0.pdf

Magnesium alginate versus proton pump inhibitors for the treatment of laryngopharyngeal reflux: a non-inferiority randomized controlled trial

OBJECTIVE
Deep brain stimulation (DBS) has considerable efficacy for the motor dysfunction of idiopathic Parkinson's disease (PD) on patient quality of life. However, the benefit of DBS on voice and speech quality remains controversial. We carried out a systematic review to understand the influence of DBS on parkinsonian dysphonia and dysarthria.


DATA SOURCES
A PubMed/MEDLINE and Cochrane systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Population, Intervention, Comparison, Outcome, Timing, and Setting (PICOTS) statements.


REVIEW METHODS
Three investigators screened studies published in the literature from inception to May 2022. The following data were retrieved: age, demographic, sex, disease duration, DBS duration, DBS location, speech, and voice quality measurements.


RESULTS
From the 180 studies identified, 44 publications met the inclusion criteria, accounting for 866 patients. Twenty-nine studies focused on voice/speech quality in subthalamic DBS patients, and 6 included patients with stimulation of pallidal, thalamic, and zona incerta regions. Most studies (4/6) reported a deterioration of the vocal parameters on subjective voice quality evaluation. For speech, the findings were more contrasted. There was an important heterogeneity between studies regarding the voice and speech quality outcomes used to evaluate the impact of DBS on voice/speech quality.


CONCLUSION
The impact of DBS on voice and speech quality significantly varies between studies. The stimulated anatomical region may have a significant role since the stimulation of the pallidal area was mainly associated with voice quality improvement, in contrast with other regions. Future controlled studies comparing all region stimulation are needed to get reliable findings.


LEVEL OF EVIDENCE
Level III: evidence from evidence summaries developed from systematic reviews.

Deep Brain Stimulation Impact on Voice and Speech Quality in Parkinson's Disease: A Systematic Review.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/lary.28841

In Reference to Anosmia and Ageusia: Common Findings in COVID-19 Patients.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9573806

Jerome R. Lechien

Papers

Platelet-rich plasma injection in the olfactory clefts of COVID-19 patients with long-term olfactory dysfunction

Magnesium alginate versus proton pump inhibitors for the treatment of laryngopharyngeal reflux: a non-inferiority randomized controlled trial

Deep Brain Stimulation Impact on Voice and Speech Quality in Parkinson's Disease: A Systematic Review.

In Reference to Anosmia and Ageusia: Common Findings in COVID-19 Patients.

COVID-19 related persistent olfactory disorders represent an unprecedented challenge