Background: Leptospirosis is an important health problem in Thailand. People infected with leptospirosis may not have any mild symptoms, whereas some people have acute and severe illnesses. It is crucial to strengthen critical patients’ diagnosis and treatment to prevent severe complications and reduce mortality. This study was performed to explore a set of parameters for the prediction of severe leptospirosis illness under routine clinical practice. Methods: A case-control study was conducted in eight general hospitals in Thailand. Retrospective collection data were used, and key information was retrieved from inpatient medical files. Patients were grouped into two severity categories, severe and non-severe infection. Backward elimination was used to reach the final multivariate model. Results: The six significant predictors identified in the study were hemoptysis , hypotension (blood pressure < 90/60 mmHg) , platelet count < 100,000/µL , white blood cell count (WBC) > 14,000/µL , hematocrit ≤ 30% , and jaundice . These predictors could correctly predict the severity of leptospirosis infection in 91.31% of the area under the receiver operation curve (AuROC). Conclusions: The results of this study showed that severe leptospirosis infections have identifiable predictors. The predictors may be used to develop a scoring system for predicting the level of severity. Leptospirosis is an emerging zoonosis of global importance and manifests with a wide clinical spectrum. Most cases are asymptomatic or mild and self-limited, with some progressing to severe and potentially fatal ,2. leptoIn Thailand, the morbidity rate of leptospirosis was from 3.26 to 7.76 per 100,000 population from 2010 to 2019. The mortality rate ranged from 0.87% to 2.49%. Most of the patients were aged 45–54 years, followed by 35–44 years, and 25–34 years. The studies presented that their occupation was mainly farming. The most prevalence was found in the Southern Region and followed by the Northeast, the North, and the Central Regions. However, the proportion of patients in the Southern Region has increased more than last year, from 36.5% to 55.6% [The symptoms are diverse, typically include fever, and are similar to those of other infectious diseases, such as the common cold, dengue fever, acute fever, headache, and muscle pain. Sometimes patients take medicine; symptoms may be improved until they progress to the second stage of the disease and are severe symptoms or complications . TraditiPrevious studies have reported prognostic factors for predicting the severity of disease, including abnormal lung sound ,9,10,11,This study was performed to explore a set of parameters for predicting severe leptospirosis illness in adult patients. Thailand is predominantly an agricultural country, located in a tropical zone; the country has a hot and humid climate which has different epidemiology from other countries. Because the transmission and clinical presentations of leptospirosis vary in different environmental and socioeconomic situations areas , predictA case-control study in prognostic research conducted by retrospective data collection. The medical records of patients with leptospirosis were registered between January 2017–December 2020. We performed the study at eight provincial hospitals located in the Northeast and Southern region of Thailand, including Loei hospital, Yasothon hospital, Buriram hospital, Roi Et hospital, Krabi hospital, Ranong hospital, Trang hospital, and Phatthalung hospital.Patients diagnosed with leptospirosis aged >15 years were confirmed by laboratory tests and admitted to general or central hospitals as mentioned previously. The Diagnostic Criteria of Leptospirosis  [on (WHO) .Clinical Criteria for Diagnosis-Acute febrile illness, chill with headache, and prostration associated with any of the following symptoms including myalgia, conjunctival suffusion, meningeal irritation, anuria or oliguria and/or proteinuria, jaundice, hemorrhages , cardiac arrhythmia or failure, skin rash;-A history of exposure to infected animals or an environment contaminated with animal urine;-Other common symptoms include nausea, vomiting, abdominal pain, diarrhea, and arthralgia.Laboratory Criteria for Diagnosis-Screening test positive in one way or another (Latex agglutination test (LA), Dipstick test, Immuno chromatography test (ICT), ELISA test for leptospirosis positive);-Confirmatory test positive in one way or another , or urine, Polymerase Chain Reaction (PCR), Microscopic agglutination test (MAT); single serum sample > 1:400/paired sera: four-fold rising, Immunofluorescent antibody test (IFA); single serum: sample IgM > 1:400/paired sera: a four-fold or greater increase in IgM and IgG antibody titers).Patients with co-infection, thalassemia, liver disease, chronic kidney disease, and patients who are missing medical records.Severe leptospirosis was defined by serological confirmation and based on WHO clinical criteria with the presence of at least one of the following criteria: serum creatinine > 3 mg/dL, respiratory failure, and death ,17.We calculated the sample size based on a multivariate logistic regression analysis of the predictive factor for severe leptospirosis from the previous study . This caThe patients were classified into two groups: the severe group and the non-severe group.Case (severe group): Patients defined by the WHO case definition of leptospirosis with at least one positive laboratory test and the presence of renal failure (serum creatinine > 3 mg/dL) and/or respiratory failure, death. Control (non-severe group): Patients defined by the WHO case definition of leptospirosis with at least one positive laboratory test did not develop any of the symptoms of severe leptospirosis listed above.During the study period, a total of 486 patients with confirmed leptospirosis were recruited. Six patients were excluded due to case notes not being found, and 480 patients were included and compatible with the inclusion definition. Of these patients, 318 (66.3%) were non-severe cases, and 162 (33.7%) were severe cases. All demographic data, clinical presentations, hemodynamic factors, and routine laboratory tests were recorded .In routine clinical practice, the traditional question of the physician is, “What prognostic indicators can be used to classify the leptospirosis infected patients into non-severe and severe groups?” This classification will affect the management of patients. In the non-severe group, outpatient close follow-up and proper education might be appropriate. In the severe group, hospitalization for disease monitoring and the proper treatment will be required.This study is under the philosophical context of prognostic prediction research. Determinants or causes of disease outcome can be called prognostic factors and aimed to explore prognostic factors of leptospirosis infection severity. The severity of leptospirosis infection (interesting outcome) was categorized into two groups. An occurrence relation can be written as follows.Demographic characteristics, clinical data, and hemodynamic factors including gender, age, smoking, alcohol, previous medical history, fever, headache, myalgia, vomiting, cough, diarrhea, abdominal pain, calf tenderness, jaundice, oliguria, anuria, dark yellow urine, redness of the conjunctiva, rash, hemoptysis, systolic blood pressure, and diastolic blood pressure within the first day of admission. Simple laboratory tests: hematological factors and biochemical factors including hematocrit, white blood cells, platelets, PMN (neutrophil), AST (Aspartate aminotransferase), ALT (Alanine aminotransferase), serum bicarbonate, total bilirubin, and serum creatinine within the first day of admission.p-value < 0.05 was considered significant. In order to identify predictors of severe leptospirosis infection, univariable analysis was performed. All variables were transformed into binary form. Continuous variables were also categorized into two binary forms. Cut-off points developed from clinically meaningful, statistically significant, using the LOWESS method and AuROC to identify the appropriate cut-off point to separate the non-severe and severe disease. Variables with a p-value < 0.05 from the univariable analysis were then tested in multivariable models using a backward elimination model, in which factors with the largest p-value  were sequentially deleted until only significant predictors remained in the final model. The ability of prediction was presented with an area under the receiver operation curve (AuROC).All data such as the baseline characteristics of the patients, clinical presentations, and simple laboratory tests were entered and recorded in an Excel spreadsheet. Numerical variables were presented with mean and standard deviation (SD) for normally distributed data. The median and interquartile range (IQR) were used for non-normally distributed data. Categorical variables were expressed as numbers and percentages. Patients’ characteristics were compared between groups using an exact probability test for categorical variables and t-tests or the Mann–Whitney U test for numerical variables. A p = 0.007), abdominal pain (p = 0.026), jaundice (p < 0.001), oliguria (p < 0.001), anuria (p < 0.001), hemoptysis (p < 0.001), SBP (p < 0.001), DBP (p < 0.001), hypotension (blood pressure < 90/60 mmHg) (p < 0.001), hematocrit (p < 0.001), WBC (p < 0.001), platelet (p < 0.001), neutrophils (p < 0.001), AST (p < 0.001), ALT (p < 0.001), bicarbonate (p < 0.001) and total bilirubin (p < 0.001) (We studied 480 leptospirosis patients in the development data set. Adult patients with leptospirosis infection were categorized as non-severe (n = 318) and severe groups (n = 162). Baseline characteristics, clinical presentation, hemodynamic, hematological, and biochemical laboratory data were observed at the time of admission. The overall mean age was 43.2 years, most individuals were male. The most common symptoms in both groups were fever (100%), and headache (100%), among the severe group, 35 (21.6%) had diarrhea and abdominal pain, 71 (43.8%) had jaundice, 12 (7.4%) had oliguria, 25 (15.4%) had anuria, 46 (28.4%) had hemoptysis, and twelve of these severe cases (7.4%) died. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the severe group were lower than in the non-severe group . Laboratory results displayed that hematocrit, platelets, and bicarbonate were lower in severe cases, while white blood cells (WBC), neutrophils, aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin, and creatinine were higher. Comparison between the severe and non-severe groups showed similar demographic data, clinical characteristics, and laboratory results, including gender, age, smoking, alcohol drinking, previous medical history, fever, headache, myalgia, vomiting, cough, calf tenderness, dark yellow urine, redness of the conjunctiva, and rash. The differences between groups included diarrhea (< 0.001) .p-value of <0.05 since there were several supported studies that indicated that these variables were significantly associated with severity. All variables were transformed into binary form. Continuous variables were also categorized into two binary forms using the cut-off points developed from clinically meaningful and statistical significance using the LOWESS method and area under the receiver operation curve (AuROC). In order to identify predictors of severe leptospirosis infection, univariable analysis was performed. Potential prognostic factors in this study were male gender, age, diarrhea, abdominal pain, jaundice, hemoptysis, hypotension (systolic blood pressure < 90 mmHg and diastolic blood pressure < 60 mmHg), hematocrit, white blood cell count, platelet count, and total bilirubin. Male gender and age were decided prior to include in the final model whether or not these variables were significantly associated with severe leptospirosis infection at the p = 0.006), abdominal pain (p = 0.024), jaundice (p < 0.001), hemoptysis (p < 0.001), hypotension (p < 0.001), hematocrit ≤ 30% (p < 0.001), white blood cell (WBC) count >14,000/µL (p < 0.001), platelet count < 100,000/µL (p < 0.001), and total bilirubin > 2.5 mg/dL (p < 0.001). Although age and gender were not statistically significant, it is found clinically significant in many studies. We decided to select this variable to include in our model. , hypotension (blood pressure < 90/60 mmHg) , platelet count < 100,000/µL , white blood cell (WBC) count > 14,000/µL , hematocrit ≤ 30% , and jaundice . These predictors could predict the severity of leptospirosis infection correctly in 91.31% of the area under the receiver operation curve (AuROC)    .Several predictors for severe leptospirosis have been identified in previous studies. This study was performed to explore a set of parameters for the prediction of severe leptospirosis illness in adult patients. We selected predictor variables by using simple clinical laboratory data in routine practice obtained on the day of admission, including demographic, clinical presentation, hemodynamic, hematological, and biochemical laboratory. The predictors could be different between geographic areas worldwide depending on the socio-demographic parameters, Leptospira species, and serovar.In our study, the significant predictors identified in the study were hemoptysis, hypotension (blood pressure < 90/60 mmHg), platelet count < 100,000/µL, hematocrit ≤ 30%, jaundice, and white blood cell (WBC) count > 14,000/µL.The previous study found that adult males were the principal risk group for leptospirosis . They haA retrospective study found that smoking was a risk factor for alveolar hemorrhage by increasing the permeability of lung capillaries, damaging the alveolar basement membrane, increasing the local inflammatory response, and respiratory distress in severe leptospirosis ,28. ThisLeptospirosis patients typically present with fever, headache, myalgia, vomiting, cough, diarrhea, abdominal pain, calf tenderness, oliguria, anuria, dark yellow urine, redness of the conjunctiva, and rash . PreviouJaundice is a common condition in severe leptospirosis. This was seen in previous studies ,12,13. IPneumonia and acute respiratory distress syndrome (ARDS) are the main respiratory symptoms of severe leptospirosis, particularly hemoptysis, which occur in 20–70% . By damaHypotension was found in 60.00% of leptospirosis patients, leading to renal and pulmonary complications. This study found that blood pressure was less than 90/60 mmHg is a predictive factor for severe leptospirosis infection, as in many studies ,9,11. HyThrombocytopenia Thrombocytopenia is a frequent complication of leptospirosis, and this condition was present in more than half of patients at the time of hospital admission . This coLeukocytosisHigher WBC and neutrophil counts have been demonstrated in patients with severe disease . LeukocyAnemia (hematocrit ≤ 30%)A decrease in hemoglobin levels is a common finding in leptospirosis patients and has been associated with severe disease and poor outcomes [. Anemia was found in severe and dead cases of leptospirosis, probably because endothelial cell damage and occult hemorrhage occurred from lung pathology. Low hemoglobin, a common finding, is caused by several factors including blood loss and hemolysis. Hemorrhage is related to death in patients with leptospirosis [. Leptospirosis patients with hemorrhage are 71.17 times more likely to die [; it leads to anemia due to blood loss, and decreased hematocrit. This was found in previous studies [. Declining hemoglobin can alert the physician of the possibility that the patient might end up with severe leptospirosis [outcomes ,44. Anemspirosis . Leptospy to die ; it lead studies ,14,15. Dspirosis .There are limitations in our study. Firstly, accurate symptoms and signs might not be captured due to the nature of the retrospective design. Secondly, some variables are various depending on age such as blood pressure or hematocrit; therefore, cut-off points may also be varied. Thirdly, since the clinical data were collected only on the day of admission, we were not able to associate the time period taken to get to the critical illness outcome from the point of enrollment. Further studies should be conducted as a prospective cohort study in order to completely collect useful data.However, the present study used clinical signs, symptoms, and simple laboratory test values which can be obtained routinely and are usually available in all levels of patient care centers to predict the severity of leptospirosis infection. This scheme may be beneficial to subdistrict hospitals, district hospitals, and provincial hospitals where confirmation is difficult due to the cost of an investigation.The severity of leptospirosis infection is significantly associated with some routine clinical parameters. Hemoptysis, jaundice, hypotension (blood pressure < 90/60 mmHg), platelet count < 100,000/µL, white blood cell (WBC) count > 14,000/µL, and hematocrit ≤ 30% are the predictors that increase severe dengue infection. They may guide clinicians to pay some attention to leptospirosis patients with these risks. In the future implications, these predictors may be used to develop a scoring system for predicting the level of severity and managing leptospirosis infection severity early in the course of the illness.


Delayed graft function (DGF) after renal transplantation is a relevant clinical problem affecting long-term organ function. The early detection of patients at risk is crucial for postoperative monitoring and treatment algorithms. In this prospective cohort study, allograft perfusion was evaluated intraoperatively in 26 kidney recipients by visual and formal perfusion assessment, duplex sonography, and quantitative microperfusion assessment using O2C spectrometry and ICG fluorescence angiography. The O2C tissue spectrometry device provides a quantitative method of microperfusion assessment that can be employed during kidney transplantation as an easy-to-use and highly sensitive alternative to ICG fluorescence angiography. Intraoperative microvascular flow and velocity in the allograft cortex after reperfusion predicted DGF with a sensitivity of 100% and a specificity of 82%. Threshold values of 57 A.U. for microvascular flow and 13 A.U. for microvascular velocity were identified by an ROC analysis. This study, therefore, confirmed that impairment of microperfusion of the allograft cortex directly after reperfusion was a key indicator for the occurrence of DGF after kidney transplantation. Our results support the combined use of intraoperative duplex sonography, for macrovascular quality control, and quantitative microperfusion assessment, such as O2C spectrometry, for individual risk stratification to guide subsequent postoperative management. Delayed graft function (DGF) after kidney transplantation is an increasing clinical problem. The rising incidence rate of DGF correlates with the introduction of expanded criteria donors (ECDs) and donation after cardiac death (DCD) in the context of organ shortage . DGF is To date, the only intraoperative quality control officially requested by procurement authorities in Europe is visual assessment of the color after reperfusion and the amount of intraoperative urine production. Doppler ultrasound is commonly added to judge macrovascular perfusion of the renal allograft ,15,16. DThe aim of this study was to evaluate different methods of intraoperative perfusion assessment for predicting DGF after kidney transplantation.n = 54). Provided the absence of exclusion criteria, namely known allergy to iodine or ICG, severe hepatic dysfunction, pregnancy, hyperthyroidism, pulmonary hypertension, and the logistical availability of both technical tools for quantitative perfusion assessment (O2C and SPY Elite) and the existence of written informed consent, 26 patients were prospectively enrolled in the study  during a time period of 2 years (October 2019–September 2021) were screened for study inclusion , organ procurement, and the transplantation procedure. Postoperative care was conducted along a standardized treatment pathway  in all pFormal evaluation of the “color after reperfusion” was performed as required by the German Organ Procurement Organization (DSO) and marked on the “Kidney Quality Form” as “homogeneous”, “marbled”, or “dark blue”.A sterile ultrasound probe , BK Medical ApS, Herlev, Denmark) was connected to the bk5000 Ultrasound System . The probe was placed directly on the surface of the graft. All anastomosis, the inflow and outflow vessels, as well as the cortex and parenchyma of the kidney were closely examined for stenosis, dissection, kinking of vessels, or lack of perfusion within all areas of the graft. The result was recorded by two experienced transplant surgeons.Cortical graft microperfusion was assessed quantitatively using the O2C device . The device has been approved as a medical device class IIa according to regulation (EU) 2017/745. Micro-Lightguide O2C combines white light tissue spectrometry  and laser Doppler flowmetry (830 nm). The probe simultaneously measures the following four parameters of microcirculation from the tissue surface: postcapillary oxygen saturation of hemoglobin , relative microvascular amount of hemoglobin ), relative microvascular blood flow  and microvascular blood flow velocity .The intraoperative measurements were conducted with a sterile LFX-29 probe (catchment volume 3 mm) that was placed directly onto the surface of the allograft. The measurements were performed, according to a standardized protocol, 5 min after reperfusion at three different sites , each for a duration of 10 s. The parameter values were immediately shown on the display of the O2C device. The measurement results from the three sites were averaged to obtain a single value to represent the kidney. The measurements were only performed once, i.e., no serial scans were performed.Subsequently, the SPY Elite System  was used for intraoperative fluorescence angiography to visualize cortical microperfusion of the graft, as described in previous studies ,18,19. TThe need for postoperative hemodialysis and the parameters of early kidney function (serum creatinine levels on postoperative days (PODs) 1–10; estimated glomerular filtration rate (eGFR) on PODs 1 and 7; cumulative diuresis in the first 24 h after transplantation; and diuresis on PODs 1, 2 and 7) were monitored. DGF was defined as the need for two or more sessions of hemodialysis postoperatively, according to Schnuelle et al. .All statistical calculations were performed using SAS statistical software, release 9.4 . Continuous variables are presented as mean values together with standard deviations or  as median values together with minimum and maximum. For categorical variables, absolute and relative frequencies (percentages) are given. The comparison of two independent groups  was performed using Fisher’s exact test or the Mann–Whitney U test, as appropriate. The CKD-EPI equation was used to estimate GFR.In order to investigate the correlation between two continuous variables of perfusion assessment, Pearson’s correlation coefficient was assessed.Furthermore, logistic regression analyses were performed in order to identify parameters potentially associated with DGF. A receiver operating characteristic (ROC) curve was generated for the O2C parameters “flow” and “velocity”. For each ROC curve, the AUC (area under the curve) was estimated together with 95% confidence intervals.p < 0.05 was considered to show a statistically significant test result.For all statistical tests, This prospective cohort study contains the assessment and associated data of 26 transplanted kidneys (22 deceased-donor kidney transplantations from donation after brain death and 4 living-donor kidney transplantations). Patient and donor characteristics are displayed in DGF occurred in five patients (19%). None of the four patients after living-donor kidney transplantation developed DGF. None of the common perioperative parameters and comorbidities were found to be significantly associated with DGF, nor was the immediate urine production after reperfusion (none vs. moderate vs. good), or the type of donation or vascularization .p = 0. 8392). The average postoperative diuresis on days 0, 1, and 2 was significantly different (p = 1.0000).The average postoperative creatinine levels of both groups were significantly different on PODs 2–10 a. There ifferent b. There p = 0.3538).Concerning the visual aspect of the graft after reperfusion , 24 grafIn all grafts, perfusion was classified as “homogenous”. No major arterial, venous, or anastomotic problems were documented.In the DGF group, surprisingly, the average value for the absolute ICG perfusion parameter Ingress was higher, but the IngressRate characterizing the quality of inflow of blood into the kidney allograft was nearly half as low as in the non-DGF group. The outflow parameters Egress and EgressRate were lower in the DGF group. However, all of the four intraoperative ICG perfusion parameters were not associated significantly to DGF .p = 0.0497), flow , and velocity  .The following O2C parameters correlated significantly positively with ICG IngressRate: SO2  . There wThe mean values for the O2C parameters “flow” c and “vep = 0.1299) for the prediction of DGF.The ROC analysis of the O2C perfusion parameter “flow” yielded an optimal cutoff value of 57.34 A.U., with a sensitivity of 100% and a specificity of 82%  for the prediction of DGF. However, these associations failed to reach statistical significance.The ROC analysis of the O2C perfusion parameter “velocity” yielded an optimal cutoff of 13.33 A.U., with a sensitivity of 100% and a specificity of 82% (AUC = 0.891, CI , The results of this prospective comparative cohort study suggest that even experienced transplant surgeons cannot predict DGF by means of intraoperative visual inspection or by duplex sonography. Quantitative perfusion assessment of microperfusion should be employed to enable an accurate individual risk stratification concerning the occurrence of DGF after kidney transplantation.Concordant with the literature, the incidence of DGF in our study was about 19%. In our study population, the common risk factors were not associated with DGF. Despite the fact that postoperative serum creatinine levels and urine outputs were significantly different in patients with a normal postoperative graft function as opposed to DGF, they vary considerably in the early postoperative period. Therefore, these parameters may not allow for the prediction of short- and long-term graft function, or the individual risk stratification of DGF. Consequently, extensive postoperative monitoring is necessary for all kidney recipients until patients at risk can be identified.As known from gastrointestinal procedures, the surgeons’ clinical judgement is of limited value in predicting postoperative outcome , presumaWe assume that quantitative intraoperative assessment of the graft’s microperfusion after reperfusion is a more precise tool for predicting postoperative early graft function because it can be interpreted as a surrogate parameter reflecting the combination of risk factors present in an individual patient , organ qFluorescence angiography with ICG is an imaging modality with a predictive ability for DGF, as supported by prospective trials ,19. The To the best of our knowledge, so far, there has not been a study comparing different modalities of intraoperative perfusion assessment during kidney transplantation with regard to a patient-specific prediction of DGF. In the present study, the ICG IngressRate correlated significantly with the O2C parameters flow and velocity. Consequently, these parameters had significantly lower values in the DGF group. We were able to deliver threshold values for the parameters flow and velocity, allowing for the prediction of DGF. The results of intraoperative risk stratification via O2C can be used to guide postoperative care. Patients with a flow exceeding 57 A.U. or a velocity exceeding 13 A.U. can be transferred to normal wards earlier, conserving valuable IMC/ICU space without endangering patient safety. On the other hand, kidney recipients with a critical microvascular flow or velocity should be monitored more closely, potentially on IMC units with a focus on systemic hemodynamics, renal blood flow, sufficient hydration, and early discussion of a percutaneous biopsy to rule out acute rejection, since IRI can trigger immunologic responses predisposing to acute graft rejection ,44.The O2C method is limited by the selective measurements and the depths of penetration. This seems to apply in particular to the parameters SO2 and rHb, derived from the tissue surface by white light spectroscopy. In case of a subcapsular hematoma or an abundance of fatty tissue, the measurements of superficial parameters might fail. Therefore, we still routinely combine microperfusion measurement with duplex sonography. Even in this comparably small cohort, the O2C method showed promising results.This pilot trial delivers a solid basis for larger prospective trials with the aim of validating O2C threshold values and investigating the optimal point in time for employing intraoperative quantitative microperfusion assessment of the renal allograft for individual risk stratification concerning postoperative transplant function in order to guide postoperative management after kidney transplantation. O2C probe specifications should be reported exactly in further publications in order to allow for a comparison between different studies.


Hypertension causing thrombotic microangiopathy (TMA) is one of the several etiologies of TMA, which causes endothelial damage and thrombosis of microvasculature, leading to hemolytic anemia, thrombocytopenia, and ischemic organ damage. Renal microvasculature involvement leading to renal dysfunction is most frequently seen in TMA but the degree of dysfunction varies with etiology. If left untreated, TMA carries a risk of high mortality, so it is extremely important for early identification of the cause of TMA. Plasma exchange is a commonly used treatment modality for TMA; however, it is not always necessary. Hypertension-induced TMA can be safely treated with antihypertensives, without the need for invasive plasma exchange. We report a 37-year-old African American hypertensive lady presenting with hypertensive emergency and TMA with rapidly progressing renal dysfunction. The patient had improvement in her platelet count after her blood pressure was reduced in a controlled manner. Thrombotic microangiopathy (TMA) is a pathological entity caused by a heterogeneous group of diseases and is characterized by abnormalities in the vessel wall of capillaries and arterioles leading to microvascular thrombosis. This results in mechanical hemolysis and platelet consumption and presents as hemolytic anemia, thrombocytopenia, and tissue injury associated most commonly with renal dysfunction . The priSevere hypertension, which is defined as a systolic blood pressure > 180 mmHg and/or a diastolic blood pressure > 120 mmHg, remains an important and preventable cause of TMA . HyperteA 37-year-old African American female presented to our emergency department with complaints of intractable nausea and non-bilious, non-projectile vomiting for a duration of two weeks; she also had frontal dull headaches. Her medical history was significant for hypertension, which was diagnosed 20 years prior and evaluation for secondary hypertension in the past had been negative. She endorsed a history of long-standing poor blood pressure control due to medication non-compliance and was on amlodipine 10 mg daily and carvedilol 12.5 mg twice daily. Other medical problems included type 2 diabetes mellitus on oral anti-hyperglycemic medication. No other significant surgical or family history was noted. On examination, her blood pressure was 230/142 mmHg without right-left arm variation and tachycardic with a pulse rate of 132/min, a respiratory rate of 18 breaths per minute, and was afebrile. She had clear breath sounds, her heart rate was regular without any murmurs, and the neurologic examination was normal. The rest of the physical examination was unremarkable.Further investigation revealed elevated blood urea nitrogen (BUN) of 49 mg/dl, creatinine of 6.74 mg/dl, hemolytic anemia with hemoglobin of 7.4 g/dl, haptoglobin < 8 g/dl, lactate dehydrogenase (LDH) of 721 IU/L, and total bilirubin of 1.9 mg/dl with normal liver enzymes. Coombs test was negative and the peripheral smear showed schistocytes, suggestive of microangiopathic hemolytic anemia. Furthermore, she was thrombocytopenic with a platelet count of 33,000 per microliter. As she had a triad of features concerning TMA, there was a high suspicion of hypertension-induced TMA due to severe hypertension at the time of presentation; however, further workup was done to identify etiology. The PLASMIC score was calculated while awaiting ADAMTS  activity results. The PLASMIC score was 4, i.e., low probability for TTP , and ADAAfter excluding all possible etiologies, our patient was diagnosed with hypertension-induced TMA. She was initiated on intravenous labetalol for management of hypertensive emergency in a controlled manner (with a target reduction in her systolic blood pressure of not greater than 25% in the first 24 hours). She was transitioned to oral antihypertensive medications with a target systolic blood pressure of not less than 150 mmHg. Hence, the patient's blood pressure slowly improved in a timely manner. She required one unit of packed red blood cell transfusion on day five of the hospital course; however, her platelets improved without any transfusion and LDH trended down with controlling her blood pressure (Table TMA has various etiologies and is diagnostically challenging. Hypertensive TMA is one of the several etiologies of TMA causing thrombosis of microvasculature leading to fragmentation of red blood cells causing microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ damage . InvolveDifferent etiologies of TMAs can be excluded based on their presentations and diagnostic workup. All the TMAs are commonly associated with a triad of features with hemolytic anemia with schistocytes on peripheral smear, thrombocytopenia, and end-organ damage. TTP can have characteristic findings of fever, altered mental status, and renal dysfunction; if it is due to acquired ADAMTS-13 deficiency, ADAMTS-13 levels are diagnostic for TTP. Shiga-meditated HUS patients usually present with diarrhea and Shiga toxin levels are diagnostic in these patient populations. Shiga-meditated HUS can be managed with supportive care. A complement factor workup can be done to rule out C-TMA. C-TMAs are treated with anti-complement therapy like eculizumab . Other sTTP and hypertensive TMA share many similarities; hence, it is important to differentiate them, as emergent plasmapheresis is required for TTP whereas severe hypertension-induced TMA can be managed by effective blood pressure control with antihypertensive medications . MedicalIn our case, our patient's etiology of hypertension-induced TMA was confirmed with her history of uncontrolled blood pressure with a severely elevated blood pressure of 230/142 mmHg at presentation; she had a classic triad of thrombocytopenia, hemolytic anemia, and renal dysfunction, with a low PLASMIC score of 4; she had normal ADAMTS-13 activity and complement levels; and workup for secondary etiologies of TMAs, i.e., HIV, hepatitis, paraproteinemia, and blood and urine cultures, was unrevealing. We treated her with antihypertensives in a controlled manner and her platelet count improved without requiring plasma exchange. The patient's kidney function remained stable and did not require initiation of hemodialysis. She was discharged and was closely followed by nephrologists for monitoring her kidney function.TMAs have various etiologies, and it is extremely important for the early identification of the cause of TMA. As TTP is a life-threatening hematological condition, it requires immediate treatment with plasma exchange; however, hypertension-induced TMA does not necessarily require plasma exchange. Due to the rarity of hypertension-induced TMA, it poses a diagnostic challenge to clinicians. Prompt diagnosis of hypertension-induced TMA and initiation of antihypertensive therapy in a timely manner have a favorable prognosis.


Conventional Doppler measurements have limitations in predicting left ventricular diastolic dysfunction (LVDD) in patients with mitral regurgitation (MR). Recently, electrocardiographic P‐wave peak time (PWPT) has been proposed as a parameter of detecting LVDD. This study aimed to evaluate the association between PWPT and left ventricular end‐diastolic pressure (LVEDP) in patients with MR.n = 40) and high LVEDP group (H‐LVEDP) . We evaluated LVDD and PWPT based on echocardiographic and electrocardiographic findings in both groups.We performed echocardiography and cardiac catheterization in 82 patients with moderate or severe MR. We classified patients into two groups: low LVEDP group (L‐LVEDP)  was significantly longer in patients in the H‐LVEDP group than in those in the L‐LVEDP group . Using correlation analysis, LVEDP was positively correlated with PWPTII . Using multivariate analysis, PWPTII was found to be an independent predictor of increased LVEDP . Using receiver operating characteristic (ROC) curve analysis, the optimal cutoff value of PWPTII for predicting elevated LVEDP was 58.9 ms, with a sensitivity of 80.0% and a specificity of 73.8% .The PWPT in lead II  and left ventricular end‐diastolic pressure (LVEDP) in patients with MR. LVEDP is positively correlated with PWPTII.Conventional Doppler measurements have some limitations in predicting left ventricular diastolic dysfunction (LVDD) in patients with mitral regurgitation (MR). Electrocardiographic P‐wave peak time (PWPT) has been proposed as a parameter of LVDD. We evaluated correlation between the PWPT in lead II (PWPT This abnormality can develop adverse cardiovascular events, such as heart failure and arrhythmia  is variable and depends on a combination of factors including regurgitation volume, myocardial status, and etiology of the underlying disorder. In asymptomatic patients with primary severe MR, the rate of progression of symptoms including left ventricular (LV) dysfunction, pulmonary hypertension, or atrial fibrillation (AF) is 30%–40% at 5 years Bonow, . Recent Electrocardiography (ECG) is used in the diagnosis and management of cardiovascular diseases. Although there are no specific ECG findings unique to the presence of diastolic dysfunction, certain ECG findings, such as electrocardiographic left ventricular hypertrophy voltage criteria and P‐wave terminal force (PWTF) in lead V1, are associated with LVDD  classification and diagnosis of heart failure were established according to the Framingham criteria , according to the standard imaging techniques recommended by the American Society of Echocardiography (ASE) , left ventricular nadir pressure (diastolic LVP), and LVEDP were measured at rest in a steady state. LVEDP was measured at end‐diastole, which was defined electrocardiographically by the onset of the next cycle's QRS wave from LVP tracing recorded with a 40‐mmHg scale. We classified the patients into two groups: the low LVEDP (L‐LVEDP) group (LVEDP <16 mmHg) and the high LVEDP (H‐LVEDP) group (LVEDP ≥16 mmHg). Aortic pressure was measured with a 4‐Fr catheter or 5‐Fr pigtail catheter via the radial artery or femoral artery. Pulmonary capillary wedge pressure (PCWP), pulmonary arterial pressure (PAP), right ventricular pressure (RVP), and right atrial pressure (RAP) were measured using a 7‐Fr Swan‐Ganz catheter via the jugular or femoral vein.2.4A 12‐lead high‐resolution surface ECG was obtained using an electrocardiograph  in all participants in the supine position with a filter range of 100 Hz, paper speed of 25 mm/s, and amplitude of 10 mm/mV. All measurements were performed by two independent cardiologists, blinded to the patients' clinical information. All patients breathed freely but were not allowed to speak during the ECG recordings. Measurements were performed using a magnifying lens. The QRS duration was defined as the interval from the start of the QRS complex until the J point. The beginning of the P wave was defined as the point at which the initial deflection of the P wave crossed the isoelectric line, and the end of the P wave was defined as the point at which the final deflection of the P wave crossed the isoelectric line. We measured maximal P‐wave duration time, minimal P‐wave duration time, and average P‐wave duration time in each case. PWPT was defined as the duration between the beginning and the peak of the P wave. In the biphasic P‐wave morphology, which was defined as a P wave with positive and negative deflections, or negative P‐wave morphology, PWPT was measured from the beginning of the P wave to the nadir of the negative deflection. In case of the biphasic or negative P‐wave morphology in lead V1, PWTF was calculated by multiplying the amplitude (milliampere) and time (millisecond) of the terminal negative component of the P wave in lead V1  curve analysis was used to calculate the PWPT value that predicted the H‐LVEDP group with the highest specificity and sensitivity.Easy R (EZR) version 1.54  was used to analyze the data Kanda, . The Kol32, p = .05). The cardiac catheterization findings are presented in Table p = .01). Systolic LVP, systolic aortic pressure, diastolic aortic pressure, mean aortic pressure, A‐wave pressure in the PCWP, V‐wave pressure in the PCWP, mean PCWP, systolic PAP, diastolic PAP, mean PAP, systolic RVP, RVEDP, and A‐wave in the RAP were found to be significantly higher in the H‐LVEDP group than those in the L‐LVEDP group (p < .05 in each case). Echocardiographic findings are presented in Table p = .52). There was no significant difference between the two groups in terms of MR severity, primary MR, secondary MR, AS, AR, and TR except of the number of patients with mitral valve prolapse . Left atrial diameter (LAD), LAVI, E/A ratio, septal e′ velocity, E/e′ ratio, and TR peak velocity were similar between the two groups (p > .05 in each case). Table V1 (p > .05), PWPTII in the H‐LVEDP group was significantly longer than that in the L‐LVEDP group . Using the correlation analysis, A‐wave pressure in the PCWP, V‐wave pressure in the PCWP, mean PCWP, and LVEDP were positively correlated with PWPTII . The mean PAP and mean PCWP showed mild positive correlation with PWTF in lead V1 . Univariate logistic regression analyses were performed to determine the clinical variables that associated with increased LVEDP. The clinical variables included body mass index, hemodialysis, paroxysmal AF, moderate or severe AS, LAD, E/e′ ratio, systolic aortic pressure, mean PCWP, average P‐wave duration, PWTF in lead V1, PWPTII, and PWPTV1. Multivariate logistic regression analyses were performed for those variable  that showed significant association with H‐LVEDP. Using multivariate analyses, systolic aortic pressure and PWPTII were found to be independent predictors of H‐LVEDP   and conducted in accordance with the guidelines of the Declaration of Helsinki on February 24, 2021.An opt‐out method on our website was used in the recruitment of participants.Reproduction in any form or by any means, electronic, mechanical, or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.None.


Electroconvulsive therapy (ECT) remains the mainstay treatment option for patients with psychiatric diseases, such as severe depression. Although various anesthetic techniques provide adequate therapeutic seizures, hyperventilation is a useful adjunct to augment seizure duration and improve seizure quality. We investigated how to efficiently use a facemask to accomplish protocolized hyperventilation and evaluate its effect on ECT seizure.n = 30) and two-handed (n = 30) groups. Following anesthesia induction under preoxygenation conditions, hyperventilation induced hypocapnia in the one-handed facemask group with manual bag ventilation was compared to that in the two-handed facemask group with assisted pressure-controlled ventilation. Ictal and peri-ictal electroencephalogram parameters and cardiovascular responses were monitored and compared between the one-handed and two-handed groups.We studied 60 patients aged ≥18 years who underwent ECT. The patients were divided into two groups according to the technique of facemask ventilation used: the one-handed (p <  0.005). At the end of ECT treatment, all parameters of blood pressure and heart rate increased significantly in both groups equally, with lower SpO2 and more ST-segment depression on the electrocardiogram in the one-handed group. Comparing baseline values before anesthesia, ECT treatment significantly depressed ST-segment in both groups, while the degree of depression in ST-segment increased significantly in the one-handed group compared to that in the two-handed group.The two-handed technique demonstrated better electroencephalogram regularity and minimized cardiovascular stress compared to the one-handed technique. These conclusions come from the fact that the one-handed technique induced a substantial volume of leaks around the facemask (201.7 ± 98.6 mL/breath), whereas minimal leaks (25.8 ± 44.6 mL/breath) with stabler and higher ventilation rate led to greater inhaled minute ventilation in the two-handed group (the one-handed group, 9.52 ± 3.94 L/min; the two-handed group, 11.95 ± 2.29 L/min; End-tidal carbon dioxide monitoring for hyperventilation can reliably ensure hypocapnia only in the two-handed group. In ECT, the two-handed technique assisted by pressure-controlled ventilation is an effective and practical method for hyperventilation to induce adequate therapeutic seizures. While, the two-handed group with sufficient preoxygenation did not cause more cardiovascular stress than the one-handed group.UMIN Clinical Trials Registry 000046544, Date of registration 05/01/2022. Electroconvulsive therapy (ECT) is a clinically proven procedure, wherein small electric currents pass through the brain and intentionally trigger a short seizure. These neurological alterations include neuronal stimulation and depolarization as well as changes in cerebral blood flow, regional metabolism, and the blood-brain barrier . ECT is To decrease the physical risks of therapeutic seizures in ECT, general anesthesia is induced with an intravenous agent and muscle relaxant combined with bag-facemask ventilation for respiratory support during the resulting apneic period , 3. PreoEvidence suggests that greater ECT stimulus intensity with respect to the seizure threshold leads to more effective treatment and faster recovery , althougSome authors have suggested that a laryngeal mask could be a first-line option to manage airway and ventilation in ECT because of its minimal leaks, better airway control, and better ventilation features , 9. In pAlthough the minimum duration of the seizure required for optimal therapeutic effects has never been established, typical recommended minimal seizure durations have been 20–25 seconds for motor response and 25 seconds for ictal electroencephalogram (EEG) response. Recently, other features of the seizure, besides duration, have emerged as promising measures of seizure quality. For example, a greater regularity predominantly shows high amplitude spikes during the slow-wave phase, greater postictal EEG suppression, and higher activation of the sympathetic nervous system . Based oAlthough major cardiovascular complications are relatively rare with ECT, they may occur in older patients and in those with underlying cardiovascular diseases. Seizure activity is characteristically associated with prolonged sympathetic discharge following initial parasympathetic discharge, resulting in tachycardia and hypertension. Thus, we also compared the acute cardiovascular response to ECT between both facemask techniques.n = 30, between March 2020 and May 2020) and the two-handed group . Written informed consent was obtained from all patients. Demographic, clinical, and infusion data were prospectively entered into the Department of Anesthesiology Information System and were retrospectively analyzed. The Institutional Review Board of the NHO Kure Medical Center approved the retrospective analysis of clinically acquired data and this study was approved by the Ethics Committees .The inclusion criteria of this the study were as follows; patients aged ≥18 years who were referred to receive index ECT by their treating psychiatrist, those receiving thiopental alone as an anesthetic . The exclusion criteria were pregnancy, chronic obstructive pulmonary disease, bronchial asthma, abuse of alcohol or other toxic substances, inability to cooperate, and current major neurological illness or injury. The patients were 60 Japanese in-patients who underwent ECT at NHO Kure Medical Center, Japan. Patients were classified into two groups according to the facemask ventilation technique; the one-handed group  in the one-handed group and to another anesthesia machine  in the two-handed group, making the patients hyperventilate. Anesthesia was induced with intravenous thiopental (2–4 mg/kg). Before administrating the muscle relaxant, a tourniquet was placed on the ankle to allow visual and tactile observation of the motor component of seizure activity in that foot. Succinylcholine (1–2 mg/kg) was administered for muscle relaxation. Muscle relaxation was monitored using a peripheral nerve stimulator. In the one-handed group, the facemask was usually held with the left hand, and the right hand was freely used to provide patients with manual ventilation using a breathing bag. The number of insufflations and ventilation volumes were arbitrarily determined by each anesthesiologist. This technique was employed in the psychiatric ward.2O; ventilation rate, 25 breaths/min) was provided by an anesthesia machine in the operating suite. The left hand was positioned on one side of the facemask in the same way as in the one-handed technique, and the right hand was placed on the other side of the facemask in an identical conformation.In the two-handed group, pressure-controlled ventilation . Assisted ventilation was performed until the seizure ended and the patient recovered from anesthesia. Complete return of neuromuscular function allowing recovery from general anesthesia was ensured using quantitative monitoring of the degree of the residual blockade, with an adductor pollicis train-of-four ratio of at least 0.90.Prior to discharge from the post-anesthetic recovery area, the patients were assessed using White’s fast-tracking score system. A score ≥ 12  and respiration rate ≥ 12 breaths/min were required before transfer to the inpatient floor.2) monitoring was performed using a capnograph in the breathing circuit that was connected to the facemask. The tidal volume was obtained using a spirometer connected directly to the facemask via a heat and moisture exchanger.During the ECT sessions, blood pressure, heart rate, oxygen saturation, electrocardiogram, and ventilation gases (oxygen and carbon dioxide) were recorded automatically before, during, and after the seizure. End-tidal carbon dioxide  and brief pulse bi-frontal electrode placement in all patients. We used the stimulus program Low 0.5 of the device, which set pulse width at 0.5 ms and automatically adjusted the lowest frequency (max 70 Hz) for longest train duration (max 8.0 s) to achieve charge dose. The length and characteristics of the seizure were determined by two-channel EEG with electrodes at the Fp1 and Fp2 sites. Motor movement was monitored by an electromyogram using the isolated limb technique with a tourniquet.ECT was administered using a ThymatronThe typical recommended minimal durations were 20–25 seconds for the motor response and 25 seconds for the ictal EEG response. Ictal and peri-ictal EEG parameters, such as regularity and postictal suppression, were manually rated using standard methods from the literature –13. IctaThe ECT stimulus and subsequent seizures both exert cardiovascular effects. First, the parasympathetic system is activated, leading to a decrease in blood pressure and heart rate at the end of the clonic phase. These events are followed by sympathetic hyperactivity, which in contrast, increases blood pressure and heart rate. The activation of the sympathetic nervous system was rated from 0 (poor) to 1 (good) (1 means increases in both blood pressure and heart rate which indicates adequate seizures).2).The cardiovascular response of patients was monitored before anesthesia, at the end of ECT treatment, and in the recovery settings, including blood pressure, heart rate, electrocardiogram, and peripheral oxygen saturation  and mean ± standard deviation. Statistical analysis was performed using EZR , a graphical user interface for R . More precisely, it is a modified version of the R commander designed to add statistical functions frequently used in biostatistics .p <  0.05.The Mann–Whitney U test and Wilcoxon signed-rank test were used to compare variables, as appropriate. Categorical variables were compared using the Fisher’s exact test. Statistical significance was set at 2 was substantially lower in the one-handed group, which seemed to contradict its poor inhaled ventilation. This discrepancy may arise due to the intrusion of external air accompanying greater leaks around the facemask during expiration in the one-handed group; therefore, these EtCO2 data were not allowed to detect CO2 release at the end of the exhaled breath or did not properly represent hypocapnia arising from hyperventilation in the one-handed group. In the two-handed group, EtCO2 of approximately 30 mmHg was reliable because of the minimal leaks shown in this study , while the degree of depression in the ST-segment increased significantly in the one-handed group (p <  0.001) compared to that in the two-handed group. In the recovery area, the one-handed group showed significantly higher blood pressure and heart rate, with lower SpO2 than the two-handed group. Following discharge from the recovery area, in the one-handed group two patients developed atrial fibrillation transiently and the other two patients had their SpO2 dropping to 89% on the inpatient floor.Before anesthesia, there was no significant difference in cardiovascular parameters between the two groups, except for SpOAppropriate anesthesia is a critical part of successful ECT which is now a clinically established therapy for selection of psychiatric patients. This therapy is usually administered two or three times a week and can be extended up to 12 times as a course of one ECT treatment, depending on the individual’s continuing review. This ECT course is determined by psychiatrists in our institution. Since the seizure threshold gradually increases over the treatment course, a relatively high stimulation dose becomes necessary, which may result in a more rapid or effective treatment but can also possibly cause accentuation of cognitive disturbances. If the maximum stimulus intensity cannot create adequate seizures and they remain missed or inadequate, efforts should be directed at decreasing the seizure threshold, increasing seizure duration, or improving seizure quality . First, Facemask ventilation is a straightforward, non-invasive airway management technique that is used as a primary mode of ventilation for short-duration anesthesia, such as ECT. Whether by one-handed or two-handed technique, 100% oxygen must be provided at an adequate flow rate to prevent rebreathing with no leaks around the facemask present to ensure adequate preoxygenation before induction of general anesthesia. In this study, we compared the effects of facemask ventilation between one-handed and two-handed techniques. In addition to fewer leaks around the facemask using the two-handed technique, a stable ventilation rate was previously determined and set with pressure-controlled ventilation, leading to greater inhaled minute ventilation in the two-handed group.2 reflects the maximum CO2 concentration at the end of exhalation, which is close to the arterial CO2 value, EtCO2 monitoring is supposed to be a useful parameter of hyperventilation during ECT procedures [2, excessive hypocapnia may increase the risk of cerebral and coronary vasoconstriction. By assessing ictal and postictal EEG parameters in the current study, both one-handed and two-handed techniques have a certain CO2 lowering effect because of an increase in seizure duration, a reduction in stimulus doses, and high numbers of ictal EEG characteristics. According to several studies, a target EtCO2 value of < 30 mmHg may not show any additional benefits of hyperventilation on seizure duration in ECT [2 of approximately 30 mmHg by the two-handed technique may be an ideal target value caused by hyperventilation because of the significantly higher regularity of ictal EEG characteristics. However, the use of a laryngeal mask may be a more effective approach because it demonstrated hyperventilation with higher ictal intensity or a higher postictal suppression index and amplitude in ECT [2 levels compared with the two-handed technique, which can be explained by the intrusion of external air accompanying massive facemask leaks during expiration; thus, EtCO2 is ineffective in monitoring hypocapnia when using a one-handed technique.Because EtCOocedures . Althougn in ECT , 18, 21.e in ECT . However2 and more ST-segment depression than the two-handed group, indicating that lower SpO2 induced by the one-handed technique subsequently elicited transient myocardial ischemia. In the recovery room, the one-handed group showed higher systolic pressure, tachycardia, and lower SpO2, which challenged the cardiovascular system, resulting in transient atrial fibrillation in two one-handed patients. The risks of cardiac arrhythmias, ischemia, and hypertension can be diminished by sufficient preoxygenation using the two-handed technique.We also explored the relationship between hyperventilation and hemodynamic parameters. ECT stimulus and the induced seizure both potentiate sympathetic discharge, which increases the heart rate and blood pressure, placing an increased demand on the cardiovascular system. Sudden onset of new changes in electrocardiograms after ECT might be reflective of myocardial ischemia due to myocardial oxygen consumption or non-uniform myocardial repolarization secondary to increased sympathetic activity due to massive release from the hypothalamus . CoustetWe demonstrated the efficacy of this two-handed technique during ECT. As a practical disadvantage, the two-handed technique depends on either an assistant or the use of pressure-controlled ventilation with an anesthesia machine to provide positive pressure ventilation. However, the use of pressure-controlled ventilation offers many advantages, including lower peak airway pressures and reduced inspiratory flow rates, which provide an additional safety measure against gastric insufflation compared with manual ventilation . Since tThere are limitations of the trial that need to be addressed. First, the current study is the inability to draw clear conclusions regarding the effect of the two-hand technique on overall ictal parameters except for regularity. This study was a single-center investigation, and our dataset was a collection of response or observations from the entire population in both groups. Due to the small number of patients, the analysis might have been underpowered to detect differences in seizure quality and side effects. The main reason for the small number was to limit the patients to those receiving thiopental alone as an anesthetic. While we used thiopental as the primary anesthetic agent in ECT, other anesthetics were selected as alternative, including propofol, the combination of propofol and remifentanil, and ketamine, in patients with compromised pulmonary status or medical complications after earlier courses of anesthesia or ECT. Various anesthetics induce different advantages and disadvantages in ECT, which makes it difficult to compare the effects of one- and two-handed techniques among patients with other anesthetics. The protocols for other anesthetics may be assessed separately. Second, this study did not include data on psychiatric outcomes or cognitive side effects. As most clinical symptoms varied on a weekly basis, the effect of ECT was not always clarified the day after treatment. Thus, it is not clear whether the response to ECT by the two-handed technique is high enough to allow for fewer treatments. Further prospective research is needed to confirm the utility of the two-handed technique in ECT safety management. Third, we used pressure-controlled ventilation in the two-handed technique. Pressure control can change the tidal volumes depending on the patient’s lung compliance, resulting in variations in both ventilatory volume during one breath, and minute ventilation. As volume control attempts to maintain ventilation by increasing pressure, it can result in the movement of a large amount of air into the stomach if the airway is not opened properly, leading to vomiting and aspiration after ECT. In pressure-controlled ventilation, the setting of inspiratory pressure, and therefore, lower peak pressure, is prospective against barotrauma and gastric insufflation.2 can effectively monitor hyperventilation in two-handed facemask ventilation systems.In this study, we investigated methods to improve protocolized hyperventilation using a facemask in ECT. The two-handed technique with minimum facemask leaks is more effective at allowing hyperventilation than one-handed ventilation, leading to better EEG regularity. While, the two-handed group with sufficient preoxygenation did not cause more cardiovascular stress than the one-handed group. Furthermore, EtCO


We evaluated the effects of visit‐to‐visit variability of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on macrovascular and microvascular complications among patients with type 2 diabetes.A total of 11 043 patients with type 2 diabetes from primary healthcare institutions between January 2010 and June 2020 were included. The visit‐to‐visit blood pressure variability was calculated using three metrics: SD, coefficient of variation (CV), and average real variability (ARV), obtained over a 12‐month measurement period. The associations of visit‐to‐visit blood pressure variability with macrovascular and microvascular complications were evaluated using multivariate‐adjusted Cox proportional hazards models, and hazard ratio (HR) with 95% confidence interval (CI) were reported.There were 330 macrovascular events and 542 microvascular events. Compared to those for participants with the lowest quartile of SD of SBP and DBP, increased risks were observed in patients with the highest quartile of SD of SBP and DBP for macrovascular complications  and microvascular complications . CV and ARV of SBP and DBP also had statistically significant associations with macrovascular and microvascular complications. The optimal variability of blood pressure target was SD of SBP <6.45 mm Hg and SD of DBP <4.81 mm Hg.Visit‐to‐visit blood pressure variability may be a potential predictor for macrovascular and microvascular complications in patients with type 2 diabetes. HighlightsEvidence on the associations between visit‐to‐visit variability of blood pressure and risks of macrovascular and microvascular complications in patients with type 2 diabetes was insufficient and controversial.This study showed that greater variability of blood pressure was related to increased risks of macrovascular and microvascular complications for patients with type 2 diabetes.Our findings identified the optimal variability of blood pressure target for patients. Clinical professionals should also remain vigilant about the visit‐to‐visit fluctuation of blood pressure. Several studies have reported that VVV of SBP is a risk factor for CVD in patients with type 2 diabetes,The total number of adults (20–79 years) with diabetes in China was up to 140.9 million in 2021, which now has the largest number of adults with diabetes worldwide.2This study was approved by the ethics committee of Huazhong University of Science and Technology (Number: 2022S004).2.1Our data were drawn from the medical records of HMPD in Community Health Service Centers from Xixiang subdistrict, Shenzhen, China. A total of 38 community healthcare centers are located at Xixiang subdistrict, covering 33 communities and providing medical service for over 1.5 million residents. According to guidelines of the HMPD, general practitioners in the community healthcare centers carry out health management for patients with diabetes in the catchment, including regular follow‐up evaluations and health examinations. The main procedures of HMPD are conducted as follows. First, general practitioners set up health records for patients with type 2 diabetes, which contain information including demographics (such as age and sex), physical checkup information , and disease‐related information (such as duration of diabetes and history of CVD). Patients are then followed up every 3 months and undergo health checkups every year. The quarterly follow‐up evaluations gather information on physical checkups , lifestyle characteristics (such as smoking status and drinking habit), treatment modalities of the patients , and disease status (diagnosed with macrovascular and microvascular complications). Annual health checkups contain diagnosis of diabetes‐related complications .2.2BP measurement period was defined as 12 months. During this period, patients were followed up quarterly, and BP was measured during each follow‐up. One BP value for each patient was recorded during each follow‐up examination. However, we performed multiple BP measurements for each patient. The procedure of obtaining BP value for patients with type 2 diabetes followed standardized guidelines, which were applicable to all general practitioners.n stands for the number of blood pressure measurements. xi stands for the blood pressure value for certain measurement.SD was used as the main metric of BPV, coefficient of variation (CV) and average real variability (ARV) were used as supplementary metrics. Detailed information for all metrics of BPV was as follows. To recognize the effects of different degrees of BPV, all patients were categorized into four groups based on their SD, CV, and ARV quartiles.2.3International Classification of Diseases, Tenth Revision (ICD‐10) coded macrovascular and microvascular complications, which derived from two sources. First, cardiovascular diseases were diagnosed by physicians based on laboratory examinations, imaging examinations, and clinical symptoms during annual health examinations. The diagnosis results were then uploaded to the medical records. Second, doctors asked patients whether they had been diagnosed with cardiovascular diseases in other medical institutions and uploaded responses to their medical records. Macrovascular complications included stroke  and myocardial infarction (ICD‐10 I21). Microvascular complications covered diabetic kidney disease (ICD‐10 E11.2), diabetic retinopathy (ICD‐10 E11.3), and diabetic neuropathy (ICD‐10 E11.4). The end point of outcomes assessment was June 2021.The outcomes of this research consisted of 2.4N = 120); (2) patients aged >80 years or < 18 years (N = 414); (3) patients who were not followed up every 3 months or had >1 missing BP value during the 12‐month measurement period (N = 1736); and (4) patients who developed macrovascular or microvascular complications during the time of 12‐month measurement period (N = 565). It is important to note that we did not exclude patients with history of CVD before the beginning of this study. A total of 11 043 patients with type 2 diabetes were included in the final analysis  patients with cancer at the time of enrollment . Statistical significance was set at p < 0.05.In the descriptive analysis, data were expressed as means (SD) for continuous variables or as frequencies (percentages) for categorical variables. We used analysis of variance or chi‐square tests to compare the baseline characteristics of participants. The survival and disease‐free probability of primary outcomes according to BPV categories were calculated using Kaplan–Meier curves, and a log‐rank test was performed to explore the differences among the groups. The proportional‐hazards assumption was evaluated using the Schoenfeld residuals test with the logarithm of the cumulative hazards function based on Kaplan–Meier estimates for each BPV category. There was no significant departure from the proportionality hazard assumptions over time. Multivariate Cox proportional hazards regression models were then used to calculate the hazard ratios (HR) and 95% confidence intervals (95% CI) between BPV and macrovascular complications and microvascular complications, where the lowest quartile of BPV was defined as the reference. To control for potential confounding factors, we adjusted for age and sex in the first model. The second model was adjusted for the demographic characteristics, lifestyle characteristics, disease information, treatment modalities of the patients, and cumulative mean of SBP and DBP. Restricted cubic spline curves were performed to visualize the associations between BPV and the risks of macrovascular and microvascular complications with the use of the “Hmisc” packages in the R program . We also performed a stratified analysis by age (<65 vs ≥65 years), sex , the use of antihypertensive drugs (with vs without), and history of CVD (with vs without). Statistical analyses were performed using SAS version 9.4  and R software version 3.6.3 (33.1Characteristics of the 11 403 patients with type 2 diabetes included in this study were shown in Table 3.2p for trend <0.05). In contrast to participants with lowest quartile of SD of SBP and DBP, higher risks were observed in patients with the highest quartile of SD of SBP and DBP for macrovascular complications  and microvascular complications . The CV and ARV of SBP and DBP also had significant associations with macrovascular and microvascular complications.There were 330 macrovascular complications and 542 microvascular complications. To demonstrate the role of BPV in CVD in more detail, we reported HR and 95% CI for macrovascular and microvascular complications across quartiles of SD‐SBP, SD‐DBP, CV‐SBP, CV‐DBP, ARV‐SBP, and ARV‐DBP in Table p for nonlinear >0.05).We further evaluated the relationships between BPV and macrovascular and microvascular events using a restricted cubic spline curve with SD of SBP and DBP as a continuous variable. Consistent with the results in Table 3.3p for trend <0.05). Only significant associations between BPV and microvascular events in patients under 65 years were observed . However, higher BPV had no significant increase in risk for CVD in patients with history of CVD . However, no significant associations were observed among patients with use of antihypertensive drugs , sex , the use of anti‐hypertensive drugs (with vs without), and history of CVD (with vs without). Among participants over 65, with the increase of the VVV of SBP and DBP, the risks of macrovascular and microvascular events were higher, and the trend was statistically significant  were more likely to participate in the regular health service. Third, our study did not cover patients without diabetes. Therefore, we could not perform analysis among non‐diabetic individuals and explore the difference on cardiovascular outcomes caused by BPV between diabetic and nondiabetic individuals. Finally, we did not consider whether the BPV could change during the follow‐up period, which might have potential effects on the results.Our study was one of the few studies conducted on BPV and CVD among Chinese patients with type 2 diabetes. Meanwhile, we acknowledged several limitations to our study. First, with a mean follow‐up of only 43.57 months, it is possible that we observed insufficient outcomes. Therefore, we might have underestimated the incidence of CVD. Second, selection of study participants who had received 12‐month follow‐up evaluation might be a source of selection bias because patients with insurance (43.40% vs 36.97%, 5In conclusion, we explored the effect of BPV on the risk of CVD among patients with type 2 diabetes and found that VVV of SBP and DBP may be potential predictors for the development of macrovascular and microvascular complications in patients with type 2 diabetes. In addition to monitoring BP targets for patients with type 2 diabetes, clinical professionals should also remain vigilant about the visit‐to‐visit fluctuation of BP.No conflicts of interest in this work.


It is not clear which Traditional Chinese Medicine- (TCM-) related elements affect primary IgA nephropathy (IgAN) progression. Here, we explored the risk factors, based on TCM syndrome elements, related to the prognosis of primary IgAN patients. 2, dialysis, or kidney transplantation) and/or eGFR decreased by >30% from baseline. Kaplan‒Meier survival analysis was used to explore the role of TCM syndrome elements in IgAN progression. Multivariate Cox regression analysis with adjustment for traditional risk factors was performed to explore TCM syndrome elements that may influence patient prognosis. The factors correlated with TCM syndrome elements in IgAN patients were further evaluated by logistic regression analysis.  We analyzed patients with newly diagnosed, biopsy-proven IgAN at a single institution from December 2013 to September 2021. Basic clinical and pathological characteristics were assessed at the time of renal biopsy. The study endpoint was end-stage renal disease (ESRD: eGFR <15 ml/min per 1.73 mP=0.012) after adjustment for traditional risk factors. Furthermore, logistic regression analysis identified being female , older age , low hemoglobin levels , and cellular/fibrocellular crescents  as factors affecting Yang-deficiency in IgAN patients.  During a median follow-up of 22.0 months, 53 (12.5%) of the 423 included IgAN patients reached the study endpoint. The main IgAN disease location elements were the kidney, liver, and spleen. The main IgAN disease nature elements were Yin-deficiency and Qi-deficiency, dampness, Yang-deficiency, phlegm, and Blood-deficiency. Kaplan‒Meier analysis identified three disease locations  and four disease natures  as elements associated with poor renal survival in IgAN patients. In multivariate Cox regression analysis, baseline Yang-deficiency was an independent risk predictor of poor prognosis in primary IgAN patients (hazard ratio 2.338; 95% confidence interval [CI]: 1.208–4.525;  Yang-deficiency independently predicts the risk of poor prognosis in primary IgAN patients. Being female, older age, low hemoglobin levels, and cellular/fibrocellular crescents were independently associated with Yang-deficiency in IgAN patients. IgA nephropathy (IgAN) is the most common primary glomerular disease in the world , 2, withAt present, the Kidney Disease International Global Outcomes (KDIGO) guidelines  recommenTraditional Chinese Medicine (TCM) uses syndrome differentiation and treatment as the core and has unique advantages in delaying the progress of IgAN –10. SyndTCM syndrome element differentiation is a new syndrome differentiation system put forward by professors Wenfeng Zhu and Yongyan Wang –13, whicIn the past, numerous studies have investigated the prognosis of IgAN in the context of TCM, mostly focusing on exploring the prognostic differences between different syndrome types , 18. How2 at the time of renal biopsy; (2) age 18 years or older at the time of renal biopsy, regardless of sex; and (3) availability of records of the four diagnoses of TCM. The exclusion criteria were as follows: (1) fewer than eight glomeruli available at biopsy; (2) secondary IgA nephropathy, such as hepatitis B-associated nephritis, anaphylactoid purpura nephropathy, systemic lupus erythematosus nephritis, and so on; (3) systemic diseases, such as diabetes, connective tissue disease, and so on; (4) patients with follow-up of less than 90 days; (5) lack of results of TCM syndrome factor evaluation; and (6) incomplete medical records. According to the inclusion and exclusion criteria, 423 patients were included in the analysis  estimated glomerular filtration rate (eGFR) ≥15 ml/min per 1.73 manalysis . This stBaseline clinical and laboratory data were collected at the time of renal biopsy. This information included sex, age, body mass index (BMI), mean arterial pressure (MAP) that was calculated as diastolic blood pressure (BP) + 1/3 (systolic BP − diastolic BP), total serum protein, serum albumin (ALB), blood urea nitrogen(BUN), serum creatinine, serum uric acid (SUA), eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation adjusted for Asian populations , total cThe pathological diagnosis was confirmed by two pathologists and was reevaluated according to the Oxford classification . Both pa2, dialysis, or kidney transplantation).The primary outcome was a composite event including the first occurrence of either a 30% decline in eGFR from the value at biopsy or end-stage renal disease , the main complaint or severe symptom, the score multiplied by 1.5; or moderate symptom, the score multiplied by 1; or mild symptom, the score multiplied by 0.7. When the sum of the score of the TCM for diagnosis of the syndrome element reaches or exceeds 100 points, these syndrome elements can be diagnosed.t-test, Mann–Whitney U test, or chi-squared test. The cumulative renal survival rate was calculated using Kaplan‒Meier survival curves, which were compared by log-rank test. Multivariate Cox proportional hazard regression models were used to analyze the factors affecting the prognosis of patients with IgAN. Multivariate logistic regression was used to analyze the correlation between TCM syndrome factors and clinicopathological indexes. A p-value <0.05 was considered statistically significant (two-sided).Statistical analysis was performed using SPSS version 26.0 . Continuous variables were expressed as the mean ± standard deviation for normally distributed data, as the median of the interquartile range (IQR)  for nonnormally distributed data, and the constituent ratio of qualitative data was expressed as frequency (percentage). Comparisons between groups were performed using Student's Of the 722 patients screened, 423 patients with biopsy-proven IgAN met the selection criteria and were included in this study . The cliThere were 155 (21.5%) patients with <90 days' follow-up who were excluded. Baseline comparisons of the 423 patients including those followed up for <90 days were shown in Supplementary After a median follow-up of 22.0 months , 53 (12.5%) patients experienced the primary outcome, including 31 (7.3%) patients with a 30% decrease in eGFR and 22 (5.2%) patients who developed ESRD.A total of 423 patients with IgAN were assessed for eight syndrome elements of disease location. Kidney was the most common location, followed by liver and spleen, while the lung, heart, stomach, Biao, and Jifu were less often involved . Eleven P < 0.05 . Multivariate Cox proportional hazard regression analysis indicated that baseline Yang-deficiency, eGFR, 24 h urinary protein, and T2 were independent risk factors for IgAN progression  as core variables were included using the entry, according to the International IgA Nephropathy Prediction Tool, recommended by KDIGO guidelines . TCM syngression .P < 0.05, P < 0.05, Since Yang-deficiency was an independent risk factor affecting the prognosis of IgAN patients, we further performed univariate and multivariate logistic regression analyses to explore the factors correlated with Yang-deficiency in patients with IgAN. Univariate logistic regression analysis showed that being female, older age, endocapillary hypercellularity, cellular/fibrocellular crescents, higher levels of HDL-C and URBC, and a lower level of ALB, SUA, and Hb were statistically significantly associated with Yang-deficiency  and non-Yang-deficiency group . At the time of renal biopsy, there were no statistical differences between the two groups in eGFR, CKD stages and 24 h urinary protein .In this study, using TCM syndrome element analysis of IgAN, the main disease location elements of IgAN were kidney, liver, and spleen, while the main disease nature elements of IgAN were Yin-deficiency and Qi-deficiency, dampness, Yang-deficiency, phlegm, and Blood-deficiency. Yang-deficiency was identified as an independent risk factor for poor prognosis of IgAN. The factors related to Yang deficiency were being female, older, having a low Hb level, and cellular/fibrocellular crescents.With a view of additional risk factors, we adjusted the prognostic factors of IgAN, as recommended by international guidelines ; we founThis study found that the proportion of patients with Yang-deficiency syndrome was higher among female than among male patients with IgAN. Previous studies have also shown that women are more common in the population with Yang-deficiency , 24, andIn this study, age was a positive predictor of Yang-deficiency in patients with IgAN, which is consistent with the TCM theory that human Yang decreases with increasing age. Chen et al. used a multicenter, epidemiological, on-the-spot investigation to study the TCM syndromes of 1,016 patients with IgAN . They foIn this study, the Hb level of patients with Yang-deficiency was lower. Previous studies also found that the level of hemoglobin in Yang-deficiency syndrome group was significantly lower than that in Qi-deficiency syndrome group and Qi-Yin deficiency syndrome group . Hb is tAnemia in TCM belongs to Blood-deficiency syndrome, Yin-deficiency syndrome, and so on. Yang-deficiency leads to insufficient gasification, which affects the movement of water valley essence in the spleen and stomach and then affects the process of blood production and transformation, resulting in Blood-deficiency. Qi is invisible, blood is the carrier of qi, and qi can be lost with the loss of blood, so blood deficiency can further aggravate qi deficiency. In TCM, Qi belongs to Yang; blood belongs to Yin. Yin and Yang are fundamental and can be transformed into each other, and Yin-deficiency can further lead to Yang-deficiency.Exploring the correlation between pathological changes and TCM syndrome elements belongs to the microscopic syndrome differentiation. Because all pathological products are tangible, they are all positive, according to the theory of TCM. Thus, there is a theory of micro-syndrome differentiation without deficiency syndrome. Because of its attribute of growth, the formation of crescent can belong to Yang . PreviouIn this study, eGFR and T lesions remained significant independent risk factors for a poor prognosis of IgAN in multivariate Cox regression analysis. However, MAP, M, E, and S lesions and the use of immunosuppressants were not statistically significantly associated in multivariate analysis. This was consistent with the results of multivariate Cox regression analysis of the full model, including race, of the International IgA Nephropathy Prediction Tool derivation cohort .However, our results in terms of other indicators differed from those of this full model with race included. In this study, 24-hour urinary protein was an independent risk factor for poor prognosis in IgAN patients, while RASB and age were not statistically significant in multivariate Cox regression analysis. The quantity of urinary protein has been shown to be associated with poor prognosis in many studies –37. The This study had some limitations. First, this study was a single-center retrospective study, with an insufficient number of included patients. Second, the median follow-up period of 22 months was relatively short.This study found that Yang-deficiency syndrome should be an independent risk factor for poor prognosis of IgAN. In turn, Yang-deficiency syndrome was related to sex, age, hemoglobin, and cellular/fibrocellular crescents. The combination of TCM syndrome elements and clinicopathological indexes may improve the clinical curative effect and delay the progress of IgAN to a certain extent.


Diabetic autonomic neuropathy is probably the most undiagnosed but serious complication of diabetes. The main objectives were to assess the prevalence of peripheral and autonomic neuropathy in a population of diabetic patients, analyze it in a real-life outpatient unit scenario and determine the feasibility of performing SUDOSCAN tests together with widely used tests for neuropathy. A total of 33 patients were included in the study. Different scoring systems  were applied to record diabetic neuropathy (DN), while the SUDOSCAN medical device was used to assess sudomotor function, detect diabetic autonomic neuropathy and screen for cardiac autonomic neuropathy (CAN). Fifteen (45.5%) patients had sudomotor dysfunction. The SUDOSCAN CAN risk score was positively correlated with the hands’ electrochemical sweat conductance (ESC), diastolic blood pressure (DBP), the level of the glycated hemoglobin, as well as with the TCNS, NDS and NSS. Performing SUDOSCAN tests together with other tests for DN proved to be a feasible approach that could be used in daily clinical practice in order to screen for DN, as well as for the early screening of CAN, before more complex and time-consuming tests. Diabetes mellitus is one of the most common metabolic disorders worldwide, resulting from a defect in insulin secretion, insulin action or both ,2. The lDiabetic neuropathy can manifest in various forms, among which the most common are distal polyneuropathy and cardiac autonomic neuropathy (CAN) . ProbablThe detection of DN in general and of autonomic neuropathy in particular, especially in their early stages, is considered to be extremely important in complication management . DevelopHowever, at present, there are limited tools to detect DN and CAN in their early stages; some tests are difficult to perform or require specially trained personnel ,11. The sudomotor function has been included by the American Diabetes Association (ADA) in the early diagnosis of autonomic neuropathy in diabetic patients. Sudomotor function is largely regulated by small, unmyelinated cholinergic sympathetic C-fibers that also regulate cardiovascular autonomic function, which may be affected earlier in patients experiencing DN .Currently, one commonly used test of sudomotor function is quantitative sudomotor axon reflex testing (QSART), but performing it imposes some technical challenges, as it demands the careful control of testing conditions and patient positioning to ensure reliability . SUDOSCAN represents an innovative, simple and non-invasive medical device which enables the assessment of sudomotor function by measuring the electrochemical sweat conductance (ESC). The apparatus can also provide a CAN risk score to forecast the possible risk of developing CAN.The main objectives were to assess the prevalence of peripheral and autonomic neuropathy in a population of diabetic patients, analyze it in a real-life outpatient unit scenario and determine the feasibility of performing SUDOSCAN tests together with consecrated tests for neuropathy. Furthermore, we intended to investigate the correlation between SUDOSCAN results and other measures of DN. The study was conducted in a specialized podiatry clinic in Cluj-Napoca, Romania, from January to March 2017. Host institution ethical approval had previously been obtained for the study, released under Nr. 01/06.03-28.04.2017, and all subjects signed written informed consent.Type 2 diabetes patients with or without symptoms of diabetic neuropathy consented to the study. Exclusion criteria included: pregnancy or nursing, amputation, implanted medical devices, actively bleeding lacerations to the arms and legs and a history of seizures or epilepsy.All patients were examined by a physician. Age, sex, weight, height, body mass index (BMI), medical history of diabetes, resting systolic and diastolic blood pressure, antihypertensive treatment, existing diabetes complications  and the value of the glycated hemoglobin were documented. The blood pressure was recorded after 5 min of rest in a supine position. The glycated hemoglobin was determined using an automatic analyzer  ,15.For every patient, a detailed foot assessment was performed as described by Boulton et al. , with thThe Toronto Clinical Neuropathy Score (TCNS), the Neuropathy Disability Score (NDS) and the Neuropathy Symptom Score (NSS) were used to evaluate DN. The TCNS was first adopted by a research group in Toronto for the screening of diabetic peripheral neuropathy (DPN) . It consThe NDS includes the ankle reflex, vibration, pinprick and temperature (cold tuning fork) sensation at both sides of the great toes, with a maximum score of 10 points. Those with NDSs of 6 points or more were considered abnormal ,18. The NSS consists of muscle weakness, sensory disturbances and autonomic symptoms and can be further divided into 17 items. Items that are answered as negative/absent are scored 0, with presence being scored as 1 point. Patients with NSSs of 3–4 points were considered to present mild symptoms, 5–6 points-moderate symptoms, while 7–10 points indicated severe symptoms .In order to minimize any possible interference and to obtain clean sudomotor function assessments, patients were instructed to avoid applying any ointments or lotions.SUDOSCAN  was used to assess sudomotor function based on reverse iontophoresis and chronoamperometry . The metThe device consists of two sets of large surface stainless steel electrodes: one set for the palms and one for the soles. Both sets were connected on a desktop computer. The patients were instructed to place both hands and feet simultaneously on the designated electrodes. Scanning took 2–3 min to complete and was completely painless. A low direct current voltage, ranging from 1 to 4 V, was incrementally applied to the electrodes, with the left and right electrodes serving alternatively as cathode and anode. At voltages ≤10 V, the thick stratum corneum is electrically insulating; however, due to their cellular bilayer, the sweat glands can transmit electrically charged ions to the skin surface and further to the electrodes (reverse iontophoresis).The current of sweat chloride ions generated in response to the incremental voltage applied can be quantified and reflects the function of the sweat gland, and hence its C-fiber innervation. Finally, this chloride ion current is measured in microSiemens (μS) and reported as ESC, expressed as the ratio of the current generated and the constant DC stimulus ,23. AccoData were presented according to the type of variables studied: quantitative variables by synthetic descriptive indicators and qualitative variables by absolute and relative frequencies. The correlation between two quantitative or categorical qualitative variables was determined using Pearson or Spearman correlation coefficients. Chi-square or Fisher’s exact tests were used for the comparison of qualitative variables, while Student’s t or Mann–Whitney tests were applied in the case of quantitative or ordinal qualitative variables, respectively.In order to control the influence of some parameters on the risk of autonomic neuropathy, a multivariate linear regression analysis was performed. p-value < 0.05 was regarded as statistically significant. The statistical analysis was performed using the SPSS application  and Microsoft Excel 2016 .A A total of 38 patients were identified through screening, but were 5 excluded due to foot ulceration. Thirty-three patients therefore consented. The demographic and clinical characteristics of the patients are presented in The mean age of the patients was 64.6 ± 16.0 years, and 18 (54.5%) were men. All patients were diagnosed with type 2 diabetes (mean diabetes duration 12.9 ± 9.3 years). Among the 33 patients, 1 (3.0%) previously had an amputation (osteotomy) and 2 (6.1%) had Charcot foot. Moreover, 10 (30.3%) had retinopathy, 8 (24.2%) arteriopathy and 2 (6.1%) had nephropathy. The mean systolic blood pressure (SBP) was 149.6 ± 23.1 mmHg, while the mean diastolic blood pressure (DBP) was 82.7 ± 9.7 mmHg. Twenty-six patients (78.8%) were receiving antihypertensive treatment, but out of these, 18 (69.2%) had an SBP > 140 mmHg, while 10 (38.5%) of them had a DBP > 90 mmHg. Among the other seven patients that did not receive antihypertensive treatment, five (71.4%) had SBP > 140 mmHg and the other five (71.4%) had DBP > 90 mmHg. The mean level of glycated hemoglobin was 7.5 ± 1.5%.According to the assessment of the sudomotor function performed by SUDOSCAN, 15 (45.5%) patients had sudomotor dysfunction. Out of these, seven (21.2%) possibly had autonomic neuropathy , while eight (24.2%) had advanced autonomic neuropathy (hands or feet ESC < 40 µS).Based on the risk of CAN (SUDOSCAN CAN risk score) estimated by SUDOSCAN, 25 (75.8%) patients were identified at possible risk for CAN, while 7 (21.2%) were found to be at high risk . Based on the TCNS, neuropathy was present in 14 (42.4%) patients. Of these, eight were mild (24.2%) and six were moderate (18.2%). No patient experienced severe neuropathy based on the TCNS . According to the NDS score, neuropathy was present in 14 (42.4%) patients, where 9 were mild (27.3%), 4 were moderate (12.1%) and 1 was severe (3%) .Based on the NSS score, neuropathy was found to be present in 26 (78.8%) patients, and where 2 were mild (6.1%), 12 were moderate (36.4%) and 12 were severe (36.4%) . The relationship between CAN risk and the ESC values, SBP, DBP, the level of the glycated hemoglobin, as well as the TCNS, NDS and NSS was examined using Pearson correlation coefficients.p < 0.001), the DBP , the level of the glycated hemoglobin , the TCNS , the NDS  and NSS   . There were no significant associations between the SUDOSCAN CAN risk score and other factors such as age, diabetes duration or SBP, with the correlation closest to positive values being between the BMI and the risk score, but still slightly in the negative field.p = 0.002). Moreover, the absence of reflexes (knee and ankle) was significantly higher with diabetic patients found to be at high risk for CAN , followed by the absence of temperature and vibration sensation, as well as by the presence of weakness. Even if the DBP and the level of the glycated haemoglobin were higher in patients at high risk, no significant statistic associations were observed  risk for CAN (SUDOSCAN CAN risk score < 50%), with the one composed of patients found to be at high risk (SUDOSCAN CAN risk score ≥ 50%). Hand ESC was significantly lower in patients at high risk for CAN (observed . p = 0.001)  . In the multiple linear regression analysis , the SUDOSCAN CAN risk score was independently associated with higher DBP and higher TCNS .CAN is a serious but mostly underdiagnosed complication of diabetes mellitus, with significant clinical and prognostic relevance . It is aThe SUDOSCAN medical device was recently developed to detect early diabetic autonomic neuropathy and screen for CAN through the assessment of sudomotor function. The SUDOSCAN CAN risk score is derived from ESC, age, height, weight and the level of the glycated hemoglobin and was reported to have significant associations with methods generally used for the investigation of CAN, such as heart rate variability testing and Ewing tests . HoweverIn the present study, CAN was assessed by measuring ESC through the SUDOSCAN medical device. ESC reflects sudomotor function, and both sympathetic and parasympathetic innervation contribute to normal sweat gland function ,27. VariDiabetic neuropathy intrinsically affects the longest fibers, such as those of the parasympathetic system. It is well known that cardiac alterations initially start with a relative increase in sympathetic tone. Denervation begins by affecting the heart at the apex, gradually impairing ventricular function and resulting in cardiomyopathy .As previously presented in our study, the CAN risk score assessed by SUDOSCAN was positively correlated with hypertension, especially with the DBP. Even if the association between CAN and hypertension has not been extensively studied in diabetic patients so far, positive correlations between autonomic dysfunction and hypertension have also been observed in other studies. A variety of hypotheses concerning the causal relationship between CAN, hypertension and diabetes have been described ,29,30. HWe also observed that more patients at no or low risk for CAN received antihypertensive treatment, compared with those that had been found to be at high risk. Although at the moment there is not a pharmacological treatment for CAN, the nocturnal administration of antihypertensive drugs may ameliorate the 24 h blood pressure profile .The SUDOSCAN CAN risk score has also been positively correlated with the level of glycated hemoglobin. Hyperglycemia is considered to play an essential role in the activation of several biochemical pathways linked to the metabolic and/or redox status, which, with impaired nerve perfusion, contribute to the development and progression of diabetic neuropathies . NeverthAn important finding of the study was that SUDOSCAN CAN risk score was also correlated with the TCNS, NDS and NSS, thus indicating an association between CAN and peripheral neuropathy. The TCNS has been preferred in some clinical trials owing to its ease of use, acceptability by patients, its ability to classify the severity of diabetic sensorimotor polyneuropathy (DSP) and its representation of the clinical changes associated with the progression of DSP ,37. TCNSCurrently, the gold standard in the evaluation of microfibers is considered to be a skin biopsy with intraepidermal nerve fiber density (IENFD). However, lately, sudorimetric techniques have undergone dramatic evolution, with ESC showing promising potential for disease detection, progression and response to therapy . QSART, The limitations of the study include a relatively small sample size and the lack of other tests for CAN , which are considered to be the gold standard for cardiac autonomic function and could be used to confirm our findings.However, this was the first study performed in Romania using SUDOSCAN as a novel test for markers of CAN, a country in which little is known about the prevalence of CAN in diabetic patients. Therefore, the use of SUDOSCAN can be considered as a promising approach for diabetic neuropathy screening in the middle-income Baltic–Balkan states.A high prevalence of sudomotor dysfunction was observed in a group of diabetic patients with or without neuropathy symptoms. Based on the results of the study, SUDOSCAN, as a simple, rapid and non-invasive test applied in order to assess the sudomotor dysfunction, proved to be a reliable method for the early screening of CAN.