Urinary albumin-to-creatinine ratio and serum albumin are predictors of acute kidney injury in non-ventilated COVID-19 patients: a single-center prospective cohort study

PURPOSE: Acute kidney injury (AKI) is a frequent complication among COVID-19 patients in the intensive care unit, but it is less frequently investigated in general internal medicine wards. We aimed to examine the incidence, the predictors of AKI, and AKI-associated mortality in a prospective cohort of non-ventilated COVID-19 patients. We aimed to describe the natural history of AKI by describing trajectories of urinary markers of hemodynamic, glomerular, and tubular injury. METHODS: 141 COVID-19 patients were enrolled to the study. AKI was defined according to KDIGO guidelines. Urine and renal function parameters were followed twice a week. Multivariate logistic regression was used to determine the predictors of AKI and mortality. Trajectories of urinary markers were described by unadjusted linear mixed models. RESULTS: 19.7% patients developed AKI. According to multiple logistic regression, higher urinary albumin-to-creatinine ratio (OR 1.48, 95% CI 1.04-2.12/1 mg/mmol) and lower serum albumin (OR 0.86, 95% CI 0.77-0.94/1 g/L) were independent predictors of AKI. Mortality was 42.8% in the AKI and 8.8% in the group free from AKI (p < 0.0001). According to multiple logistic regression, older age, lower albumin, and AKI (OR 3.9, 95% CI 1.24-12.21) remained independent predictors of mortality. Urinary protein-to-creatinine trajectories were diverging with decreasing values in those without incident AKI. CONCLUSION: We found high incidence of AKI and mortality among moderately severe, non-ventilated COVID-19 patients. Its development is predicted by higher albuminuria suggesting that the originally damaged renal structure may be more susceptible for virus-associated effects. No clear relationship was found with a prerenal mechanism, and the higher proteinuria during follow-up may point toward tubular damage

GestaltMatcher Database - A global reference for facial phenotypic variability in rare human diseases

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.</p

Diabetic Cardiovascular Autonomic Neuropathy, the Handgrip Test and Ambulatory Blood Pressure Monitoring Parameters: Are There Any Diagnostic Implications?

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. Cardiovascular reflex tests (CARTs) are the gold standard in the diagnosis of CAN, but the handgrip test is no longer recommended to be performed. Previously, the inverse association between the presence of hypertension and handgrip test abnormality was demonstrated and hypertension as major cause for excessive diastolic blood pressure rise during handgrip testing in diabetic individuals proposed. The aim of the present study is to describe more precisely the association between handgrip test and hypertension by performing ambulatory blood pressure monitoring (ABPM) among diabetic patients. A more comprehensive evaluation of the relationship between cardiovascular autonomic function, hypertension and the handgrip test was targeted using heart rate variability (HRV) analysis. Our study involved 163 patients with diabetes. Cardiovascular autonomic neuropathy was assessed by the CARTs and sustained handgrip test was performed. All patients underwent ABPM and HRV analysis well. CAN was diagnosed in 69 patients. Significant associations were found between the diastolic blood pressure increase in response to handgrip exercise and the 24-h (rho = 0.245, p = 0.003), daytime (rho = 0.230, p = 0.005) and night-time (rho = 0.230, p = 0.006) mean systolic and 24-h diastolic (rho = 0.176, p = 0.034) blood pressure values, systolic blood pressure load (rho = 0.252, p = 0.003) and systolic (rho = 0.236, p = 0.005) and diastolic (rho = 0.165, p = 0.047) hyperbaric impacts. Higher values of ambulatory blood pressure monitoring parameters are associated with greater increases in diastolic blood pressure during isometric handgrip exercise. Diastolic blood pressure elevations during the handgrip test are also correlated, in order to diminished heart rate variability parameters attributable to parasympathetic dysfunction highlighting the pivotal role of sympathetic overactivity in evolving handgrip test results. Our study provides further evidence on the inverse association between handgrip test abnormality and hypertension in diabetic patients

Differenciáldiagnosztikai problémák amyotrophia diabetica fennállása esetén – esetismertetés [Diabetic amyothrophy: problems of differential diagnosis – a case report]

A 74 éves, 2-es típusú cukorbetegségben szenvedő férfi beteg klinikai felvételére fél éven belül bekövetkező 25 kg-os fogyás, a test számos részén megfigyelhető, pörkkel fedett sebek, nagyfokú gyengeség miatt került sor. A tumorirányú vizsgálatok negatív eredménnyel zárultak. A bőrjelenségek ismételt bőrgyógyászati konzílium véleménye alapján bullosus pemphigoidnak bizonyultak. Biklonális gammopathia igazolódott, a cristabiopszia eredménye ugyanakkor nem igazolt malignus infiltrációt. Fél évvel későbbi, ismételt klinikai észlelése során motoros neuropathia tünetei kerültek előtérbe. Betegünk esetében összességében amyotrophia diabetica volt diagnosztizálható, a szerzők a differenciáldiagnosztikai aspektusok mellett a több kóroki tényező együttes fennállása mellett kialakuló, súlyos fokú neuropathia lehetőségére hívják fel a figyelmet. | The 74 years old male patient with type 2 diabetes was admitted to our department due to 25 kg weight loss, widespread skin injuries and severe weakness. Investigations towards malignant tumours were negative. According to repeated dermatological consultations, skin alterations were diagnosed as bullous pemphigoid. Biclonal gammopathy was found while no malignancy was detected by bone biopsy. During his second clinical hospitalization, half a year later the clinical picture was dominated by symptoms of motor neuropathy. Altogether, diabetic amyotrophy was diagnosed. The authors provide a review on differential diagnostic aspects, as well as highlighting the probability of neuropathies due to more simultaneous pathogenetic factors

Indokolt lehet-e plazmaferezis, ill. opioid készítmény kiegészítő adása a neuropathia diabetica kezelésében? [Is there any indication for plasmapheresis and opioid therapy in the treatment of diabetic neuropathy? – a case report]

A szerzők egy 72 éves, évtizedek óta 2-es típusú cukorbetegségben szenvedő férfi esetét ismertetik, diabeteses polyneuropathiája 30 éve ismert. Az évek során makrovaszkuláris szövődmények következtében több alkalommal történt coronarographia, alsó végtagi PTA és stentimplantáció. Aktuális klinikai felvételére kedvezőtlen szénhidrátanyagcsere-helyzet (HbA1c : 11%), ismételt elesések miatt került sor. Az obezitásban (BMI: 39,2 kg/m2) is szenvedő beteg esetében a korábban beállított SGLT-2-gátló, illetve GLP-1-receptor-agonista kezelés dózisát emelték, aminek hatására vércukorértékei céltartományba kerültek. Mind a négy végtagra kiterjedő, disztális túlsúlyú fájdalmas neuropathiás panaszai kapcsán a beteg már évek óta kombinált oki és tüneti kezelésben részesült: alfa-liponsav és benfotiamin, valamint duloxetin és pregabalin szedése mellett is típusos alsó végtagi, dominálóan éjszakai neuropathiás fájdalmai jelentkeztek. Neuropathiavizsgálat során súlyos hypaesthesiás típusú szenzoros károsodás volt igazolható mind a négy végtagon a Neurometerrel (Neurotron Inc, Baltimore, USA) mért áramérzet-küszöbértékek, a Vibratip, a Tiptherm, a kalibrált hangvilla és a monofilamentum, továbbá a Q-Sense (Medoc Ltd., Yamat Rishai, Israel) készülékkel mért hőérzet-küszöbértékek tekintetében is. Közepesen súlyos fokú kardiovaszkuláris autonóm neuropathia is fennállt. A gyakori elesések hátterében kóroki tényezőként egyrészt a súlyos fokú szenzoros hypaesthesia, másrészt az ortosztatikus hipotónia (32 Hgmm) volt igazolható. Az eddigiekben alkalmazott négyes kombináció nem kielégítő terápiás effektusára való tekintettel kiegészítő kezelésként plazmaferezist alkalmaztak, emellett a kezelést opioid származék adásával egészítették ki. Következtetés: A neuropathia diabetica egyes ritka esetekben járhat egyidejűleg extrém mértékű neuropathiás károsodással és neuropathiás fájdalommal. A kezelésben alapvető a megfelelő glikémiás kontroll és fontos az oki és tüneti szerek alkalmazása. Az eset arra hívja fel a figyelmet, hogy emellett egyes esetekben szükséges lehet a terápia opioid készítményekkel, valamint plazmaferezissel történő kiegészítése. | The authors report a 72-year-old patient with type 2 diabetes (T2DM), who was diagnosed with diabetic neuropathy 30 years ago. During the years, he underwent coronarography, lower limb PTA and stent implantations several times due to macrovascular complications. This time, the patient was admitted to the hospital due to poor glycaemic control (HbA1c : 11%) and falls. To achieve better metabolic control in the obese patient (BMI: 39.2 kg/m2), we titrated doses of SGLT-2-inhibitor and GLP-1 receptor agonist therapy. The patient has already been on combination therapy for severe painful diabetic neuropathy including both pathogenetically oriented (benfotiamine and alpha-lipoic acid) and symptomatic (duloxetine and pregabalin) treatment options. Despite, he still suffered from typical neuropathic pain. On neuropathy examination, severe sensory impairment was confirmed at all extremities by diminished current perception thresholds measured by Neurometer (Neurotron Inc.), by the Vibratip, Tiptherm, the monofilament, the tuning fork, as well as by higher thermal perception thresholds detected by Q-Sense (Medoc Ltd.). Moderate cardiovascular autonomic neuropathy was also detected. Based on the neuropathy studies, the frequent falls complained by our patient might have resulted from his severe distal sensorimotor neuropathy and orthostatic hypotension (32 mmHg). As the so far administered fourfold combination therapy did not provide sufficient pain relief, the patient underwent plasmapheresis and opioid therapy was initiated with sufficient result. Conclusions: Diabetic neuropathy may be characterized by extremely severe hypaesthesia and neuropathic pain simultaneously. Good glycaemic control is a cornerstone in the treatment of diabetic neuropathy. When treating painful diabetic neuropathy, both pathogenetically oriented and symptomatic therapy should be implemented. Besides, plasmapheresis and opioid supplementation should be considered for some patients