Magnetic resonance imaging (MRI) offers the possibility to measure local and regional indices of aortic function. However calculations of these indices usually require blood pressure (BP) values. Up to now, because of its easier availability, brachial BP was used instead of local aortic pressure. The SphygmoCor Xcel system  estimates aortic pressure non-invasively. It consists in a MRI compatible brachial cuff connected via a hose to a recording unit and computer. The aim of this study was to compare brachial and central BP values given by SphgymoCor Xcel with the standard 2 meters hose and a 6 meters hose more suitable for central BP assessment during MRI.After 5 min rest supine, BP was measured simultaneously on both arms with one 2 m SphgymoCor Xcel and one 6 m SphgymoCor Xcel. Arms were randomly assigned. Tubing were then interchanged (cuffs unchanged) and recordings repeated.2=0.96, 0.91, 0.78, 0.97, 0.85, 0.95, 0,96 respectively, p < 0.001 for all.). Bland Altman plots showed no statistical difference between 2 and 6 m for brachial and central SBP, DBP, PP values. However there was a difference between AP and Aix recorded with 2 m and 6 m hose .38 patients were studied (63% men). Seven (18%) were treated for hypertension, 2 (5%) for diabetes and 3 (11%) for dyslipidaemia. Median age was 36.8 years (28.5-58.4). Brachial Systolic BP (SBP), Diastolic BP (DBP), Pulse Pressure (PP), central SBP, DBP PP, augmented pressure (AP) and augmentation index (Aix) from the 2 m and 6 m device were strongly correlated (RSphygmoCor Xcel device with a 6 m hose, brachial and central BP shows no statistical difference with the standard 2 m hose, allowing data to be collected during MRI exams. However other parameters using waveform morphology such as AP and Aix are not so reliable.


Recently there has been a progressive loss of specialty related skills for nephrologists. Among the skills we find the kidney biopsy that has a central role in diagnosis of renal parenchymal disease. One of the causes might be the belief that the kidney biopsy should be performed only in larger Centers which can rely on the presence of a renal pathologist and on nephrologists with a large experience. This trend may increase in the short term procedural safety but may limit the chance of in training nephrologists to become confident with the technique.We evaluated renal biopsies performed from May 2002 to October 2016 in our Hospital, a mid-sized facility to determine whether the occurrence of complications would be comparable to those reported in literature and whether the increase in the number of biopsy performing physicians including nephrology fellows which took place since January 2012, after our Nephrology Unit became academic, would be associated to an increase of complications or a reduction of diagnostic power of renal biopsies. Three hundred thirty seven biopsies were evaluated. Patients underwent ultrasound guided percutaneous renal biopsy using a 14 G core needle loaded on a biopsy gun. Observation lasted for 24 h, we evaluated hemoglobin levels 6 and 24 h and kidney ultrasound 24 h after the biopsy.p = 0.004). We found no correlation between diagnosis, kidney function and complication rates; hypertension was not associated to a higher risk in complications. The increase of biopsy performing personnel was not associated to an increase in complication rates  or with an increase of major complications .Complications occurred in 18.7% of patients, of these only 1,2% were major complications. Complications were more common in female (28%) compared to male patients  (Kidney biopsy can be safely performed in mid-sized hospitals. Safety and adequacy are guaranteed even if the procedure is performed by a larger number of less experienced nephrologists as long as under tutor supervision, thus kidney biopsy should become an integral part of a nephrology fellow training allowing more widespread diffusion of this technique. Nephrology is a specialty in need of resuscitation according to a forum published on Kidney International in 2009 . The forIn this single center retrospective observational study we evaluated patients undergoing renal biopsy from May 2002 to October 2016. During this time frame our Nephrology Unit in ICS Maugeri SpA became academic (January 2012) thus acquiring nephrology fellows which were actively involved in clinical practice including renal biopsy performance. Aim of our study was evaluating whether the increase in number of biopsy-performing physicians including nephrology fellows from January 2012 would be associated to an increase of complications or a reduction of diagnostic power of renal biopsies and to determine whether the complication rate in our average sized hospital would be comparable to rates reported in literature by larger hospitals.This study evaluated kidney biopsies performed at ICS Maugeri from May 2002 to October 2016. Our cohort included 337 patients, all of which had consented to the biopsy procedure. Only adult patients were included whereas pediatric patients and patients undergoing a biopsy as a diagnostic procedure in the presence of a solid renal mass were excluded.For all the included patients the following data, available in medical charts, were collected: age, gender, medical history, concomitant medications, bio-humoral testing such as serum creatinine, hemoglobin, platelet count, proteinuria, hematuria, needle size, number of glomeruli including sclerotic glomeruli per biopsy specimen, immunofluorescence report, number of passes performed, microscopic observation of freshly acquired specimen, diagnosis, presence of complications including complication severity.Complications were classified as follows.Minor complications: arteriovenous fistula, minor hematoma spontaneously reabsorbed, gross hematuria, post-procedural hypotension.Major complications: need of blood transfusions, hematoma requiring drainage.All patients needing to perform a kidney biopsy were admitted the day prior to the procedure in order to perform preliminary exams. Patients known to be on anticoagulant or antiplatelet therapy were contacted in order to stop medication at least 1 week prior the procedure switching to heparin as needed.Routine laboratory tests performed on admission included complete blood count, coagulation testing, biochemistry . On admission all patients also underwent a renal ultrasound in order to confirm the presence of adequate sized kidneys excluding the existence of anatomical abnormalities which may represent contraindication to the procedure.Biopsies were performed 24 h after admission in the early morning.All patients underwent real time-ultrasound guided percutaneous renal biopsy according to local practice. Briefly patients were placed in the prone position with a pillow under the abdomen in order to reduce lumbar lordosis (transplanted patients were placed supine); blood pressure and heart rate where checked before the procedure and pressure cuff was left for subsequent measures during the procedure. Before starting a peripheral vein was cannulated to guarantee a rapid infusion line in case of intra-procedural hypotension. Two operators, an assistant and a more experienced nephrologist acting as supervisor were always present. The lower pole of the left kidney was located by ultrasound subsequently the skin was disinfected with 10% povidone iodine, prior to injecting local anesthesia with 1% lidocaine. A small incision was made to facilitate introduction of the biopsy needle. All biopsies were performed using a Bard automated biopsy gun loaded with a 14 Gauge tru-cut needle. Under real time-ultrasound guidance the needle was advanced by the second operator until reaching the lower pole of the kidney and subsequently fired and removed.Until 2012 each core was only observed macroscopically for size, after January 2102 observation was systematically performed under a stereomicroscope with 20X magnification to verify the presence of glomeruli in order to avoid other passes if not needed. After the procedure a renal ultrasound was systematically performed to evaluate the presence of hematomas. A flat dressing and ice were applied on the area. After the biopsy, patients were asked to stay in prone position for the next 2 h and kept bed bound until the next morning. Every half hour blood pressure and heart rate were monitored and the first void was checked for hematuria. Complete blood count was performed 6 h after biopsy and repeated at 24 h from procedure. A ultrasound control was performed in every patient 24 h after procedure. If no complications occurred patients were discharged the day after the procedure and afterward contacted for results.Descriptive statistics were performed for all the collected variables. Frequencies and percentages or means and standard deviations were reported for qualitative or quantitative variables, respectively. Ordinal variables were summarized as median, minimum and maximum of the distributions. Statistical associations between factors potentially influencing the occurrence of biopsy-related complications and complications were tested by means of chi-square test. Mann-Whitney U test was used to assess differences in the median number of passes needed to grant adequate diagnostic power of the biopsy before and after 2012. A statistical significance level of 0.05 was chosen. SPSS Statistical Software was used for the analyses.Three hundred thirty seven patients undergoing a kidney biopsy in our Unit between May 2002 and October 2016 were included in the study. 50.7% (171 patients) underwent a renal biopsy between May 2002 and December 2011 and 49.3% (166 patients) form January 2012 to October 2016  and 237 males (70.3%); mean age at the time of biopsy was 58.0 ± 15.8 years. Forty seven patients (13.9%) were positive for hepatitis C virus (HCV). Hypertension occurred in 70.6% of patients; among hypertensive patients 10.4% were defined as having a severe hypertension based on the need to take more than three antihypertensive agents.p = 0.993 . Based on previously published data [The diagnostic power of the bioptic procedure was not reduced starting form 2012. Our results show a trend towards a reduction of non diagnostic biopsies, 7 (4.1%) vs 2 (1.2%) before and after 2012 respectively, associated to a simultaneous statistically significant reduction of the median number of passes required to gain an adequate core (p < 0.005) thus confirming the observation that female patients are at higher risk of developing procedural associated complications.The results of our study show that the incidence of complications, both minor and major was significantly higher in females (28%) compared to males (15%) (p < 0.05). Also the severity of hypertension had no correlation with the complication rate.Two hundred fifty eight patients were on antihypertensive treatment and 35 were classified as having severe hypertension based on the need to take more than three antihypertensive agents to achieve adequate blood pressure control. Interestingly complications were more common in normotensive compared to hypertensive patients (p = 0.588). Our population included 9 cases of amyloidosis. Although the diagnosis of amyloidosis has been suggested to be a predisposing factor for bleeding due to acquired coagulation factor deficiencies and to increased stiffness of vessels due to amyloid deposition we were not able to demonstrate an increase in biopsy related complications in this population compared to control group. No increase in complication incidence was found in patients with amyloidosis, activation of the immune system, oncologic conditions or vascular diseases nor did we find any difference in complication rate based on the presence of a primitive or secondary glomerular disorder.To evaluate the existence of a possible correlation between kidney function and complication rate we next divided our cohort based on creatinine value stratifying patients with creatinine values below 2 mg/dl and above 2 mg/dl. Our data show that complications were not increased in patients with more severe renal function impairment (Kidney biopsy is a very important diagnostic tool for nephrologists and has always been considered a characteristic of nephrologist’s job description. Recently however kidney biopsy has been increasingly reserved to larger hospitals with an experienced nephrologist and pathologist to guarantee maximum procedural safety and diagnostic power or it has been taken over by other specialists. The result is a reduced appeal of Nephrology specialty for young trainees. Eventually young nephrologists miss the technical expertise to perform a renal biopsy due to lack of training. In line with the guidelines given by the American Society of Nephrology our middle sized academic hospital has since 2012 promoted the training of young nephrologists even in biopsy performing.In our study we evaluated if procedural safety and diagnostic power of the renal biopsy in a middle sized hospital could be comparable to those reported by larger hospitals also assessing procedural safety and adequacy of biopies performed by less experienced operators, including fellows, under tutor supervision.Our data showed minor complications in 17.3% of biopsies and major complications in 1.2% of cases. This incidence rate was in line with the one reported by larger centers especially if we consider that our definition of minor complications included millimetric sized hematomas which are very often considered an unavoidable consequence of the bioptic procedure just as much as microscopic hematuria . FurtherWe acknowledge that the present study has many limitations. First of all it is a retrospective study and the biopsies considered were performed in two rather long periods of time. We did not find a significant dfference in outcomes however many variables could have affected outcomes such as different patients characteristics, different technical approach and different quality of ultrasound machines. Patients undergoing kidney biopsy in the two study periods had similar characteristics and no differences were found in kidney diseases. We used the same ultrasound machine throughout the period examined, a machine that was only older when used by young trainees. The only remarkable difference in the techique used to perform the kidney biopsy was the analysis of the tissue by light microscopy to check for glomeruli.Since a16G needle is perfectly adequate for obtaining good histology sample it could be used when a more inexperienced operator is performing the procedure, increasing the safety of the procedure.In conclusion performing kidney biopsies in middle sized Hospitals appears safe and garantees good diagnostic power. The increase in number in biopsy-performing personnel, including unexperienced nephrology fellows, does not increase complication rate or severity and is associated to comparable diagnostic power. Thus the kidney biopsy should be an integral part of nephrology fellows training allowing a more widespread diffusion of the technique to smaller and more peripheral centers.


Fungal airway infection (airway mycosis) is increasingly recognized as a cause of asthma and related disorders. However, prior controlled studies of patients treated with antifungal antibiotics have produced conflicting results. Our objective is to measure the effect of antifungal therapy in moderate to severe adult asthmatics with positive fungal sputum cultures in a single center referral‐based academic practice.We retrospectively evaluated 41 patients with asthma and culture‐proven airway mycosis treated with either terbinafine, fluconazole, itraconazole, voriconazole, or posaconazole for 4 to >12 weeks together with standard bronchodilator and anti‐inflammatory agents. Asthma control , peak expiratory flow rates (PEFR), serum total IgE, and absolute blood eosinophil counts before and after antifungal therapy were assessed. In comparison, we also studied nine patients with airway mycosis and moderate to severe asthma who received standard therapy but no antifungals.p = 0.004), increased PEFR  and markedly reduced serum IgE levels  and blood eosinophil counts . Reduction in symptoms, medication use, and relapse rates decreased as duration of therapy increased. Asthmatics on standard therapy who did not receive antifungals showed no improvement in asthma symptoms or PEFR. Antifungals were usually well tolerated, but discontinuation (12.2%) and relapse (50%) rates were relatively high.Treatment with azole‐based and allylamine antifungals was associated with improved asthma control (mean change in asthma control 1.72–2.25; Antifungals help control symptoms in a subset of asthmatics with culture‐proven airway mycosis. Additional randomized clinical trials are warranted to extend and validate these findings. The hygiene hypothesis suggests that allergic diseases such as asthma, and chronic, as well as seasonal atopic rhinosinusitis (CRS) may be a consequence of maladaptive immune reactions to microorganisms and other environmental agents beginning in childhood Bacillus subtilis (subtilisins) when added to laundry detergents can promote severe, but reversible asthma Its diverse clinical presentations suggest that asthma is a manifestation of many distinct pathophysiologies Aspergillus oryzae are alone sufficient to induce major features of asthma, including T helper type 2 (TH2) cell recruitment to lungs, airway hyperresponsiveness, goblet cell metaplasia, airway eosinophilia, and elevated serum IgE in a manner that requires intact proteinase activity A. oryzae proteinases drive dendritic cell maturation in a way that favors TH2 cell expansion and the neutralization of cytokines such as IL‐12 that antagonize TH2 responses H2 cells. These proteinases also induce macrophage and airway epithelial cell‐based antifungal immunity The most intensively studied allergenic proteinases are those derived from fungi. Given intranasally to mice, the major secreted proteinases from the fungus, H2 responses) can be demonstrated in many asthmatics, suggesting that rather than innocuous colonization, the airway fungi are producing an immunologically and physiologically significant infection that we term airway mycosis Many different proteinases  are found in household dust, but these enzymes are either denatured and no longer exhibit proteinase activity or exist in levels insufficient to induce allergic inflammation and disease. Thus, it is unlikely that these proteinases have a direct role in asthma pathogenesis Multiple clinical trials have explored the possibility that suppressing or even eliminating airway mycosis with antifungals may improve asthmatics. For example in one study 32 weeks of treatment with itraconazole was associated with improvement in Asthma Quality of Life Questionnaire (AQLQ) scores, rhinitis scores, and peak airflow while simultaneously reducing total serum IgE levels Given the positive result of one randomized clinical trial We conducted a retrospective chart review of 50 asthma patients referred to the Michael E. Debakey VA Medical Center Allergy & Immunology Clinic for refractory asthma between 2012 and 2016. All patients whose sputa grew fungi were offered antifungal therapy in addition to standard care. Forty‐one patients agreed to be treated with antifungals including terbinafine, voriconazole, itraconazole, fluconazole, or posaconazole for at least 4, and up to 52 weeks. Nine patients whose sputa contained fungi were treated with standard bronchodilators and anti‐inflammatory agents but did not receive antifungals because they did not tolerate these, refused antifungal therapy, or had medication incompatibilities. Chart review included patients with at least 1 follow up within 1 year of their initial visit. The retrospective chart review was approved by the Baylor College of Medicine and the VA Institutional Review Boards.Patients referred for moderate to severe asthma underwent routine evaluation for airway mycosis as previously reported by our group Patients receiving a diagnosis of asthma with airway mycosis were treated with one of five antifungals, terbinafine, voriconazole, itraconazole, fluconazole, or posaconazole. Therapy was initiated using standard dosing for invasive fungal disease, adjusting the dose based on trough drug levels, when available. Treatment was continued for a minimum of 12 weeks when tolerated. Patients treated for at least 4 weeks were included in the analysis. Liver function was measured 2 weeks after the initiation of therapy. Patients were examined 12 weeks after initiating therapy except where disease severity dictated earlier and more frequent evaluation. In addition to obtaining a medical history focused on asthma symptoms and general well‐being, vital signs, oxygen saturation, and peak expiratory flows were measured at each clinic visit. Telephone calls were used to assess patient progress and adjust medication dosage based on drug levels or evidence of toxicity.In addition to general demographics, we collected data on the types of fungi cultured , length of therapy, relapse rates, and antifungal therapy discontinuation data. To gain insight into the effectiveness of antifungal therapy, we estimated asthma severity and measured peak expiratory flow rates, serum total IgE, and absolute blood eosinophil counts before and after the initial course of therapy. Because smoking might modify treatment response, we analyzed data from never‐ and ever‐smoker subgroups separately. The same information was collected at the same intervals from the nine patients with airway mycoses that were not treated with antifungals.The primary outcome measures of this study were (A) asthma control as defined by the National Heart, Lung and Blood Institute (NHLBI) analog assessment scale for asthma control: 1 = very poorly controlled; 2 = not well controlled; and 3 = well controlled Response to therapy was defined as improvement in any one or combination of the following subjective variables: improved breathing and/or decrease in cough, sputum production, wheezing, rescue inhaler use, anti‐inflammatory controller inhaler use, or decreased us of systemic steroids. These data were recorded 1–4 weeks prior to initiation of antifungal therapy and at the next clinic visit 4–12 weeks after initiating treatment.Asthma relapse was defined as the reappearance of cough, productive sputum, shortness of breath, wheezing, or any combination of these symptoms up to 24 weeks after cessation of antifungal therapy.p values were two‐sided, with p < 0.05 considered statistically significant.Comparisons of two sets of paired data were made using the Wilcoxon signed‐rank test or Mann–Whitney test, as appropriate, to determine clinical and immunological responses to antifungal treatment. A log‐rank test was performed to compare the relapse‐free probabilities between groups. All analyses were performed using Stata v11.1 software  or Prism v5.0.2 . All We reviewed 50 patients whose sputum cultures contained fungi. All were on standard bronchodilator and anti‐inflammatory inhaler treatment at the time of referral to the Allergy and Asthma subspecialty clinic. Forty one of these patients received a minimum of 4 weeks antifungal therapy and had at least 1 follow up visit. Nine patients continued to receive standard care but were not treated with antifungals because of medication intolerance, incompatibility, or refusal to accept this treatment and were used as control group to the antifungal treated patients.Approximately half of our subjects were never smokers; the other half identified as former or active smokers (ever smokers). The mean age of the 50 patients was 59 years, 77% were male, and 54% were Caucasians. All patients received inhaled steroids and the majority received at least one course of oral steroids Table . Sputum Many patients received more than one antifungal. The duration of treatment was controlled by the decisions of the treating physicians and VAMC pharmacy policies. Most patients including 14 never‐ and nine ever‐smokers were treated with voriconazole Table . ApproxiDiscontinuation rates were highest for voriconazole 21.4%) in the never smoker group (Table % in the p = 0.004)     Fig. .p = 0.0313; Fig. We next assessed clinical follow up in nine asthmatics that we identified with airway mycosis who were referred to the Allergy and Immunology Clinic and given standard of care, but not treated with antifungals. The reasons for lack of antifungal therapy included intolerance, refusal, or medication incompatibility. Although these patients continued to receive standard asthma therapy , chart review of asthma severity using the same parameters described for the antifungal‐treated group showed no significant changes Fig. A. MoreovThe patients referred for this study reported asthma symptoms for most of their adult lives. Despite close adherence, they had failed to respond to conventional therapy and often had progressive disease that required frequent, extended courses of systemic corticosteroids. In many, their significant symptomatic response to antifungal therapy was accompanied by reduced serum IgE, reduced peripheral eosinophil counts, and improved peak expiratory flow values regardless of smoking status. Thus, evidence of improvement in these treatment‐refractory patients is particularly noteworthy. Our novel methods for culturing fungi from sputum Although fungal infections have been implicated pathophysiologically in diverse allergic airway diseases The study by Agbetile, et al. Early in the treatment of asthmatics when the patient is receiving both corticosteroids and azole antifungals it is important to recognize that both itraconazole and voriconazole inhibit the activity of the hepatic cytochrome P450 enzyme CYP3A4. A consequence of this inhibition is that the half‐lives of corticosteroids are prolonged, resulting in a more potent anti‐inflammatory steroid effect in patients treated both with azole antifungals and a corticosteroid Prolonged therapy with anti‐fungal agents is key to their effectiveness. Our data indicate that the duration of therapy with azole‐class antifungals was an important predictor of medication response. Amongst azole antifungals, relapse was almost universal in patients treated for less than 8 weeks. In contrast, relapse occurred in less than 50% of patients when therapy was extended to 12 weeks and in less than a quarter of patients treated for longer than 16 weeks  This material has not been published in whole or in part elsewhere. (ii) The manuscript is not currently being considered for publication in another journal. (iii) All authors have been personally and actively involved in substantive work leading to the manuscript, and will hold themselves jointly and individually responsible for its content.


Simultaneously, heart rate (HR), breathing frequency (BF), mean arterial blood pressure (MAP), and arterial oxygen saturation (Sao2) were recorded.This observational case-control study was conducted at the Neonatal Deparetment of Children's Hospital Ljubljana between December 2012 and April 2014. It included 35 newborns with CHD and 30 healthy age- and sex-matched controls. CHD were assessed echocardiographically and divided into acyanotic and cyanotic group. RSO2 in the left brain hemisphere , right brain hemisphere , and the kidney . RSO2 in the intestine did not significantly differ between the groups. HR, MAP, and Sao2 also did not differ between the groups, whereas BF was significantly higher in the CHD group . Between cyanotic and acyanotic group, we found no significant differences in rSO2 of any tissue.Newborns with CHD had significantly lower rSOMonitoring tissue oxygenation by NIRS could enable a timely detection of hemodynamically important CHD. Congenital heart defects (CHD) occur in about 1% of newborns, causing blood flow obstruction or blood shunting of different degree . Right-t2) is near-infrared spectroscopy (NIRS). The method assesses oxygenated and deoxygenated hemoglobin by comparing scattered and absorbed near-infrared light  was conducted at the Neonatal Department of Children’s Hospital Ljubljana, Slovenia, from December 2012 to April 2014. The newborns' parents signed the informed consent, and the ethical approved was obtained from the National Ethics Committee . The investigation conforms to the Declaration of Helsinki principles.We included 35 term newborns with critical structural CHD of different types who required surgical or transcathetral procedure in the first year of life. CHD were diagnosed by pediatric cardiologists using clinical examination and echocardiography. The exclusion criteria were pulmonary or neurological disease, perinatal asphyxia, acute illness, prematurity, and congenital abnormality other than CHD.We divided the CHD group into two subgroups: the group where the clinical signs are accompanied by cyanosis (16 patients), including the following defect types: tetralogy of Fallot (n = 4), pulmonary atresia (n = 3), double outlet of the right ventricle (n = 3), transposition of the great arteries (n = 3), atrioventricular septal defect (n = 3); and the group without cyanosis (19 patients), including the following defect types: ventricular septal defect (n = 7), pulmonary stenosis (n = 5), aortic stenosis or coarctation of the aorta (n = 5), hemodynamically important atrial septal defect (n = 2).The control group comprised 30 healthy age- and sex-matched newborns without CHD hospitalized at our department. Their venous blood was taken to detect conditions not affecting the investigated outcome, such as infection, benign systolic murmur, poor feeding or weight gain, or congenital urinary tract defects. The exclusion criteria were the same as for the study group.o2) assessed by noninvasive pulse oximetry.CHD were diagnosed by ALOKA ProSound Alpha 10 ultrasound system  by a pediatric cardiologist specialized for ultrasonographic examinations. Tests were performed with newborns lying comfortably in a peaceful environment. Electrodes  were placed on the thoracic wall to measure the heart rate (HR), breathing frequency (BF), mean arterial blood pressure (MAP), and hemoglobin oxygen saturation in arterial blood .Venous blood samples were analyzed in the laboratory of the Department of Clinical Biochemistry, University Children's Hospital, University Medical Centre Ljubljana. Serum glucose concentration was measured by an enzymatic UV test (hexokinase method) using AU 400 analyzers ; hemoglobin and hematocrit using Sysmex XT 2000i analyzer ; and partial pressure of CO2 was measured using in vivo optical spectroscopy . The system consists of four sensors that are fastened to the skin. Each sensor has a near-infrared light-emitting diode and two detectors of the light reflected from the superficial and deeper tissues. These two signals are subtracted to assess deep tissue oxygenation.RSO2 assessment, symmetrically over the left and right frontal head area; for intestinal rSO2 assessment, to the abdomen 3 cm to the left of the umbilicus; for kidney rSO2 assessment, lumbally 2 cm from the medial line. RSO2 was calculated from the differential signals obtained from these two sensors, expressed as the venous-weighted per cent oxygenated hemoglobin [oxygenated hemoglobin/total hemoglobin (oxygenated hemoglobin + deoxygenated hemoglobin)] ] ,18. To ct test; between not normally distributed variables with Mann-Whitney test; and between categorical variables with χ2 test with Yates’ continuity correction. To control for false positives, the P values were adjusted using a multivariate permutation procedure  or medians and ranges, while categorical variables were summarized as proportions (with their 95% CI). Significance of the relationship between normally distributed numerical variables was tested by Welsh two-sample rocedure . The corP < 0.001) (There were 23 (66%) boys in the CHD group and 16 (53%) in the control group. CHD patients and controls did not significantly differ in demographical characteristics  or in la< 0.001) .2 in the left (67 ± 11% vs 76 ± 8%) and right (68 ± 11% vs 77 ± 8%) brain hemisphere than controls  and the intestine, but the latter difference was not significant  (Newborns with CHD had significantly lower rSO= 0.174) .2s in the left and right brain hemisphere , intestine , and kidney  were significantly positively correlated  Sare found . Contrary tissue .2 in the brain and kidney than newborns without CHD. Moreover, both groups showed a strong correlation between rSO2 of the left and the right hemisphere. Contrary to our hypothesis, no significant differences in rSO2 were detected between the cyanotic and acyanotic group.Newborns with preoperative CHD had lower rSO2 of different tissues in newborns with various critical cyanotic and acyanotic CHD and compared them to healthy newborns. We hope that these results will contribute to accurate and timely assessment of CHD, which is of crucial clinical importance as patients with CHD exhibit changes in brain structure later in life, resulting in neurologic complications and cognitive and behavioral impairment (To the best of our knowledge, this is the first study that assessed and correlated rSOpairment ,18,20-222 in the CHD group than in controls found in our study is in accordance with several other studies (2 than in healthy newborns; yet, their infants were mechanically ventilated and thus already compromised. We, on the other hand, included newborns who, except cardiac support in terms of diuretics or vasodilators, did not receive any other medication. In fact, the physiological parameters in the CHD group, except for the increased BF, were normal and comparable to controls. Increased BF implies child's distress; in a newborn with CHD, tachypnea is caused by increased pressure in the pulmonary veins resulting from blood flow obstruction to the left ventricle or raised end-diastolic pressure in the left ventricle. It may also be caused by increased fluid volume in the lung bloodstream in large left-to-right shunts (Lower brain rSO studies ,20,23. T studies ,20,23. C studies  that most shunts .2 in the CHD group points to impaired oxygen supply.Although the exact limit of the appropriate brain oxygenation as assessed by NIRS is debatable and has not been accurately established ,10,23,252 of other organs, but none included healthy controls. Amigoni et al (2 as a screen for echocardiographic PDA evaluation; while Owens et al (2 and kidney dysfunction in infants with CHD undergoing cardiac surgery. Our study is the first to compare regional oxygenation of tissues other than the brain between newborns with CHD and healthy controls. As expected, the kidney rSO2 was lower in newborns with CHD than in controls; also, a significant positive correlation between the brain rSO2 and the kidney rSO2 was found.Organs other than the brain, which is affected by autoregulation mechanism, might be more seriously affected by inadequate perfusion . Severalni et al  monitoreni et al  proposedns et al  showed a2 between the CHD group and controls also cannot be explained. The failure to detect lower intestinal rSO2 could be attributed to optode placing over a thin neonatal abdominal wall above intestinal loops containing pigments, such as bilirubin, and air; both known to strongly affect the rSO2 value (2 measurements.We hypothesized that oxygenation would be lowest in the intestine due to redistribution of blood flow, but did not confirm the hypothesis. The lack of differences in the intestinal rSOO2 value . Also, t2 in any tissue between the cyanotic and acyanotic group. We therefore speculate that newborns with CHD have different hemodynamics than healthy newborns, irrespective of the CHD type. On the other hand, the cyanotic group might have had a low degree of deoxygenated blood shunting, not affecting the oxygenation to a greater extent than in the acyanotic group.Contrary to our hypothesis, despite the trend toward lower oxygenation in the cyanotic subgroup, there were no significant differences in rSOpost-hoc power analyses showed that rSO2 comparison between patients with CHD and controls for the kidney and right and left brain hemisphere had power >80%, but our study was underpowered to detect statistical significance for other possibly existing associations. Some other methodological limitations of our study should also be considered. The main problem remains the high spatial, temporal, and inter-subject variability of NIRS (2 values between the right and the left hemisphere emphasizes the accuracy of our data. It has also been suggested that the intervention outcome in a specific patient should be assessed, rather than absolute rSO2 values (The most important limitations of our study are retrospective design, single center experience, heterogeneous study population, and small sample size. Regarding primary analyses,  of NIRS ,12,23,272 values ,12,23,282 over a larger surface area instead of point probes.In conclusion, we showed that, NIRS was able to detect lower tissue oxygenation and could be regarded as a useful additional non-invasive clinical tool for monitoring and follow-up of newborns at risk for non-optimal brain oxygenation. The most distinctive advantage of NIRS is its non-invasiveness and easy applicability . Future


Chronic kidney disease is a common condition in the general population, particularly among older adults. Renal impairment is in turn associated with metabolic and nutritional derangements and with increased risk of cardiovascular disease.To compare the metabolic, nutritional, and cardiovascular impact of reduced kidney function between patients with and without known renal disease.We enrolled consecutive outpatients (age ≥65 years) with reduced renal function who were divided into two groups: Group A with history of renal disease and Group B with unknown renal disease. Metabolic and nutritional parameters, including involuntary body weight loss (BWL) in the previous 6 months, mineral metabolism, inflammatory indices, and left ventricular mass index (LVMI), were evaluated.n = 39, M: 24, F: 15) showed greater BWL with a significant reduction of 25-hydroxyvitamin D, transferrin, cholinesterase, albumin, and LVMI with respect to Group B (p < 0.01). Conversely, Group B  showed significantly increased intact parathyroid hormone, total cholesterol, low-density lipoprotein, triglycerides, and C-reactive protein when compared to Group A (p < 0.05).A total of 76 patients were enrolled. Group A (The positive history of renal disease may negatively impact on several metabolic and nutritional parameters related to increased cardiovascular risk among older adults. Chronic kidney disease (CKD) is a common condition and it is increasing worldwide, particularly in adults aged ≥70 years, where the prevalence in the United States, Europe, and China is 47, 35, and 28%, respectively , 2. The 2 and, with higher prevalence, when it is <45 ml/min/1.73 m2 ]. We also calculated the body weight loss in the previous 6 months.Body weight was determined to the nearest 0.1 kg using a calibrated digital scale. Body mass index (BMI) was calculated by the formula [weight (kg)/heightBlood samples were collected after an overnight fasting of at least 12 h. In all patients, the levels of fasting plasma glucose, total serum cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, Blood Urea Nitrogen (BUN), serum calcium, phosphate, sodium, potassium, serum uric acid, iron metabolism, including transferrin, cholinesterase, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured using standard automated techniques. Serum albumin was determined by bromocresol purple method. Parathyroid hormone was measured using a two-site assay that measures “intact” hormone (iPTH) (pg/mL) and 25-hydroxyvitamin D (25-OH Vit D) (ng/mL) by radioimmunoassay. LDL cholesterol was calculated using the Friedewald equation: LDL = total cholesterol − HDL − (triglycerides/5). Arterial blood gas analysis was performed using a blood gas analyzer (Nova Phox Plus C). We have measured albuminuria in 24-h urine .M-mode 2D echocardiographic examinations by a single experienced sonographer in the echocardiography laboratory and using a standard institutional protocol were completed. Commercially available instruments  equipped with 2.25- to 7.5-MHz imaging transducers were used. The subjects were in the left decubitus position, and the sonographer was blinded to all clinical details of the patients . All ech® SPSS® Statistics 18 for Windows® software . The normality of variables was tested by the method of Kolmogorov–Smirnov test for normal distributions. All continuous variables were expressed as mean ± SD, and categorical variables were expressed as number (percentage). Student’s t-test or Mann–Whitney U-test was performed to determine differences between groups. Binomial test or Chi-square test was used for comparison of categorical data. Pearson’s or Spearman’s correlation was used to determine the relationship and the strength of association between the variables in bivariate correlation. Potential confounders, such as age and gender, were included in the analyses when comparing the two groups. A p value < 0.05 was considered statistically significant.Data management and analysis were performed using the IBMThe study included 76 consecutive patients, 29 females and 47 males, with a mean age of 70 ± 5.4 years.Patient’s characteristics are shown in Table p < 0.0001), cholinesterase (UI/mL) (p = 0.003), transferrin (mg/dL) (p = 0.001), hemoglobin (g/dL) (p = 0.015), 25-OHVitD (ng/mL) (p < 0.001), and pH (p < 0.0001) with respect to Group B (Table p = 0.009), higher LVMI g/m2 (p < 0.0001), BUN (mg/dL) (p < 0.001), iPTH (pg/mL) (p = 0.03), total cholesterol (mg/dL) (p = 0.02), LDL (mg/dL) (p = 0.04), triglycerides (mg/dL) (p = 0.02), CRP (mg/dL) (p = 0.046), and ESR (mm/h) (p = <0.0001)  p < 0.000, cholineThe results obtained in the present study would suggest that age-related compared to renal disease-related decline in renal function differentially impacts on patients’ metabolic and nutritional parameters, and possibly on cardiovascular disease (CVD) risk.Chronic kidney disease is a common feature among older adults and less frequently progresses to ESRD with respect to younger patients . CVD is 2 or less , although the eGFR was comparable between the two groups.Only patients in Group B achieved the lipid target range recommended by the European and Canadian guidelines , althoug2 as indicative of moderate CKD (stage 3), independent of age. It has been recognized that the physiological aging process of the kidney leads to a loss of GFR at a rate of about 1 ml/min/1.73 m2 per year after 40 years of age   .The complications related to reduced eGFR would be abnormal sodium balance causing hypertension, a blunted erythropoietin axis causing anemia, and disturbed calcium and phosphate balance causing secondary hyperparathyroidism and metabolic acidosis .2 is normal, 60–89 ml/min/1.73 m2 is reduced, and ≤60 ml/min/1.73 m2 is always abnormal, independent of the presence of kidney damage , although also patients with no history for disease (Group B) showed depletion of vitamin D. In particular, Group A showed a more pronounced depletion of vitamin D with respect to Group B, being associated with a small but significant increase of iPTH. Moreover, Group A showed a worsening trend of nutritional status, with a significant reduction in albumin and cholinesterase levels, lower BMI, and greater BWL in the previous 6 months. In Group A, we also found a significant reduction in hemoglobin levels, although these values were within the therapeutic range for patients with eGFR ≤60 ml/min , and they damage , 38. Thiy damage , 40.The average eGFR is variably decreased in older adults, as a consequence of biological aging and underlying comorbidities . In someAs supported by other evidences, in older patients with CKD we should consider not only the eGFR and the presence of proteinuria but also the underlying renal disease , 45. MorWe acknowledge the limitations of our study. The small sample size might have limited the possibility to recognize associations between patients’ clinical characteristics. In this light, the present cohort of patients may not be representative of the entire CKD outpatient population. In particular, we included a large proportion of patients on antiplatelet and antihypertensive therapies and on statins and the potential impact of hypertension, hypercholesterolemia, and their treatments on LVMI may have potentially confounded our results. Although both groups were affected by hypertension, Group A had a higher prevalence of this condition probably determining the significant difference observed in LVMI. Approximately 40% of patients in Group B suffered hypertension. This may be associated with the reduction of eGFR. However, in contrast with Group A, patients in Group B were treated with antihypertensive monotherapy, showing blood pressure values within normal range.In spite of comparable eGFR, older adults with underlying renal disease have a worse nutritional and metabolic balance with respect to patients with negative history. This is reflected by the presence of alterations of metabolic and inflammatory profile and by impaired cardiovascular index.Integrated care for older adults with loss of renal function should go beyond a focus on reduced eGFR or proteinuria and include consideration of underlying cause of kidney disease.Based on our results, it might be helpful to prospectively evaluate the impact of nutritional alterations on clinical outcomes and health-care costs in older adults with impaired renal function.SL, MIA, MM, and AM made substantial contributions to conception and design and interpretation of data; SA, DM, and AD made substantial contributions to acquisition of data; and CL, PA, and MC made substantial contributions to analysis of data. All authors participated in drafting the article or revising it critically for important intellectual content. All authors gave final approval of the version to be submitted.The authors are responsible for the content and writing of the paper. The manuscript is not under consideration for publication elsewhere.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewers CO and AD and handling Editor declared their shared affiliation and the handling Editor states that the process nevertheless met the standards of a fair and objective review.


Vascular hyperreactivity is a risk factor and a factor predicting hypertension (high blood pressure). Unlike other continents where several studies were carried out, it has rarely been studied in black Africa in general and in Cameroon in particular.2, Man-Withney, Wilcoxon's signed ranks and logistic regression tests were used for statistical analysis.Vascular reactivity was measured by the cold test. Vascular hyperreactivity was defined as an increase in blood pressure > 20 mmHg for systolic and/or > 15 mmHg for diastolic. KhiA total of 31 hypertensive and 31 normotensive patients matched by age and sex participated in this study. Vascular hyperreactivity was present in 77.4% hypertensive patients and 51.6% normotensive patients. There was a significant association between vascular hyperreactivity and hypertension . The median arterial pressure was higher in responders compared to non-responders in the normotensive group. Age > 45 years, female sex, obesity and family history of hypertension appeared to be associated with vascular hyperreactivity, but only in normotensive patients.Vascular hyperreactivity appears to be a risk factor for high blood pressure in black Cameroonians. It appeared to be associated with low blood pressure, age, sex, obesity and family history of hypertension but this was only in the normotensive. High blood pressure (HBP) is defined by the World Health Organization (WHO) as a systolic blood pressure (SBP) above or equal to 140 mmHg and/or diastolic blood pressure (DPB) above or equal to 90 mmHg. HBP is a major public health problem in the world. According to the WHO, the estimated average prevalence of hypertension in 2008 among adults aged 25 and over was 40%, the highest rate being recorded in Africa 46%). According to Kearney et al, 79 million people in sub-Saharan Africa were hypertensive in 2000 and there would be twice as many people affected by 2025 . There a%. Accord® HN289) and the size was measured with a gauge to the nearest centimeter. Body mass index (BMI) was calculated by making the weight ratio on the square of the height. Blood pressure was measured using automatic tensiometers (OMRON® M2 Basic and M3). We also looked for physical signs that could lead to secondary hypertension. The vascular reactivity was measured by the cold test with cold water. After a rest period of 15 minutes in supine position, BP was measured three times with a one-minute interval. The average of these three measures was considered the basic BP. Then the temperature of the water was measured (3-6°C) and the subject was invited to immerse his left hand to the wrist for 60 seconds. BP was measured at 60 seconds of immersion after which the subject could extract his hand. Finally, BP was measured every minute for 4 minutes after hand extraction. Vascular hyperreactivity was defined as an increase in SAD > 20 mm Hg and/or PAD > 15 mm Hg. Statistical analyzes were performed using Statistical Package for Social Sciences (SPSS) version 20.0. Khi2, Fisher and logistic regression tests were used to measure the association between qualitative variables. The Pearson correlation was used to measure the association between the quantitative variables. The Man-Whitney and Wilcoxon signed rows tests were used for median comparison. The threshold of statistical significance was p < 0.05.The study was carried out at the Yaoundé Teaching Hospital (CHUY). It was approved by the Institutional Committee for Research Ethics (CIER) of the Faculty of Medicine and Biomedical Sciences (FMSB) of the University of Yaounde I. We received research authorization from the CHUY and we obtained informed consent from each participant. In the study we included hypertensive subjects aged 18 to 60 years, not taking antihypertensive drugs and clinically healthy normotensive patients who were matched to the hypertensives by age and sex with a ratio of 1:1. Patients with a history of heart disease, chronic obstructive pulmonary disease, chronic kidney disease and peripheral neuropathy, pregnant women, subjects with grade 3 HA (PA ≥ 180/110) and those with signs of Secondary HTA were excluded. Age, gender and background were recorded during the interview. The weight was measured using an electronic weighing scale with an accuracy of 100 grams  were higher in responders compared to non-responders in the normotensive group. Age > 45 years (1.15 (0.20 - 6.71); P = 0.87), female sex (3.07 (0.47 - 20.05); P = 0.24), obesity (1.90 (0.23 - 15.71); P = 0.55) and family history of HBP (3.73 (0.70 - 19.99); P = 0.12) appeared to be associated with vascular hyperreactivity in normotensive patients. This was not the case in hypertensive patients. There was a significant association between vascular hyperreactivity and hypertension ( (3.21 (1.07 - 9.63); P = 0.03).All 31 hypertensive subjects and 31 normotensive subjects participated in this study. Explaining the fact that the race, the average age of participants in our study was 45 ± 9 years and 42 ± 9 years, respectively, in hypertensive and normotensive patients, is consistent with Benetos and Safar in France in 1991 and Elias et al in Nigeria in 2015 , 11. As Benetos and Safar found lower proportions (64% and 47% respectively in hypertensive and normotensive) despite lower thresholds of hyperreactivity (16 mmHg for SBP and 12 mmHg for DBP). This shows once again that black people are more reactive to the cold test compared to Caucasian and black race is a risk factor for hypertension , 15. BMIVascular hyperreactivity appears to be a risk factor for high blood pressure in Cameroonian black people. It could depend on the baseline status of the vascular system, age, female gender, obesity and family history of hypertension but only in normotensive patients. This suggests that these factors play an important role in the early stages of development of hypertension and that their influence becomes negligible when it becomes manifest.Vascular hyperreactivity was identified as a risk factor in many studies conducted in other continents than Africa.Vascular hyperreactivity appears to be a risk factor for high blood pressure in Cameroonian black people.The authors declare no competing interest.


Routine use of cardiac output (CO) monitoring became available with the introduction of the pulmonary artery catheter into clinical practice. Since then, several systems have been developed that allow for a less-invasive CO monitoring. The so-called “non-calibrated pulse contour systems” (PCS) estimate CO based on pulse contour analysis of the arterial waveform, as determined by means of an arterial catheter without additional calibration. The transformation of the arterial waveform signal as a pressure measurement to a CO as a volume per time parameter requires a concise knowledge of the dynamic characteristics of the arterial vasculature. These characteristics cannot be measured non-invasively and must be estimated. Of the four commercially available systems, three use internal databases or nomograms based on patients’ demographic parameters and one uses a complex calculation to derive the necessary parameters from small oscillations of the arterial waveform that change with altered arterial dynamic characteristics. The operator must ensure that the arterial waveform is neither over- nor under-dampened. A fast-flush test of the catheter–transducer system allows for the evaluation of the dynamic response characteristics of the system and its dampening characteristics. Limitations to PCS must be acknowledged, i.e., in intra-aortic balloon-pump therapy or in states of low- or high-systemic vascular resistance where the accuracy is limited. Nevertheless, it has been shown that a perioperative algorithm-based use of PCS may reduce complications. When considering the method of operation and the limitations, the PCS are a helpful component in the armamentarium of the critical care physician. Critically ill patients often receive extended hemodynamic monitoring with measurement or estimation of cardiac output (CO) as an aid for guiding fluid and vasopressor therapy. With the introduction of the pulmonary artery catheter by Swan et al., measurement of CO became available at the bedside by a thermodilution technique . HoweverIn the following years, transpulmonary thermodilution techniques have been introduced, still allowing for a measurement of CO while less invasive, only requiring a central venous and an arterial line that are often used for standard hemodynamic monitoring in intensive care patients . HoweverTo further reduce the invasiveness of CO measurements, several new techniques have been evaluated and introduced into clinical practice in recent years. These include “non-invasive methods” and “less- or minimal-invasive methods.”The non-invasive methods estimate a CO, i.e., from changes in thoracic electrical impedance, from radial applanation tonometry (T-Line), or from finger blood pressure cuffs .The less- or minimal-invasive methods estimate a CO from an arterial pulse contour waveform –7 and re2™: similar to Pulsioflex™, PULSION Medical Systems, Feldkirchen, Germany; EV1000™: similar to Vigileo™, Edwards LifeSciences, CA, USA). The algorithm of the LiDCOrapid™ is also used in the LiDCOplus™ System  that can measure CO by a lithium dilution method. Furthermore, a pulse contour analysis is available, that is calibrated by an esophageal Doppler included in the same monitor . The use of the pulse contour analysis without the Doppler calibration is not possible.In addition, some systems have been introduced that combine a pulse contour analysis with an internal reference method and are referred to as “calibrated pulse contour methods.” Two transpulmonary thermodilution systems are available that track CO by pulse contour analysis after an initial calibration with algorithms, which are similar to the ones used in the stand-alone uncalibrated PCS  and heart rate. Heart rate is usually equal to the pulse rate. The input of the device consists of a pressure measurement, the arterial waveform. Obtaining the pulse rate and hence the heart rate from the waveform is usually a straight-forward task by counting the number of upstrokes of the pressure curve over time. The calculation of the other required parameter, the SV is a difficult task since a pressure measurement must be converted to a volume measurement. This is done by estimating flow that is integrated over time leading to a volume. Deriving a flow from a pressure parameter requires concise information of the pressure–volume relation in the arterial system and especially the aorta. The systems use a refinement of Otto Franks Windkessel model dating back to 1899 that incorporates arterial impedance (Za), arterial compliance (Ca), and systemic vascular resistance (SVR)  and mean arterial pressure.Over the years, the FloTrac™ algorithm has been refined. In the current software version 4.0, the internal database has been expanded, and an improved SV tracking has been added, electronically eliminating, and interpolating abnormal beats, i.e., in premature complexes.The Pulsioflex™ monitor is connected to the proprietary ProAQT™ transducer attached to a standard radial or femoral arterial catheter. A start CO may be determined by two methods. A CO may be manually entered if available from an external calibration method, i.e., echocardiography. Alternatively, the monitor may be “autocalibrated” thus estimating a CO from an internal database based on patient’s characteristics .For the continuous measurement of CO, the arterial waveform is sampled at a frequency of 250 Hz. The systolic portion of the arterial waveform is identified, and the area under the curve (AUC) integrated from pressure over time. At the start of CO measurements, an internal calibration factor is calculated from the CO and AUC. Since the AUC is proportional to CO, an increase of the AUC corresponds to an increase of CO, and a decrease of AUC corresponds to a decrease of CO. The algorithm also takes SVR and arterial compliance into account to improve measurements. The internal calibration factor basically corresponds to the arterial impedance.via an analog output. The system can be calibrated by manually entering a CO from a reference method.This system is connected to any arterial line without a dedicated catheter. No special pressure transducer is required; the monitor can receive the pressure signal from a conventional vital signs monitor The algorithm of this system for determining CO relies on calculation of SV by means of a so-called “pulse power analysis,” which is independent of the shape of the arterial pressure curve. This algorithm determines a nominal aortic volume from a monitor-internal nomogram, in which age, gender, height, and other parameters are considered. The obtained volume is multiplied by an exponential function, that is affected by arterial blood pressure and an aortic compliance determined from an internal reference.This system uses an algorithm called “pressure recording analytical method” (PRAM). The approach of this system is different from the other methods because the arterial impedance that is required for calculation of SV is estimated from perturbations of the arterial pressure waveform and not derived from internal nomograms based on demographic parameters . No exteThe estimation of the arterial impedance relies on a complex theory of perturbations and is obtained from a morphological analysis of the pulsatile and the continuous components of the pressure waveform . When thFurther calculations for SV use the area under the systolic part of the pressure curve divided by the arterial impedance. CO is obtained by the multiplication of pulse rate and SV.A good arterial waveform signal is an important prerequisite for correct measurements. Over-dampened and under-dampened waveforms indicate that the dynamic response characteristics of the arterial catheter system are insufficient and therefore not suitable for analysis . It has A rapid flush test has been proposed to analyze the intrinsic resonance frequency of the catheter–transducer system and to verify for correct response characteristics , 13. AftMost systems rely on the recognition of the dicrotic notch to identify the systolic portion of the pulse waveform. In instances of over- or under-dampened catheter–transducer systems, the dicrotic notch may not be identified correctly, possibly leading to incorrect measurements .Although these systems are designed to be used with any arterial waveform, concerns have been raised that femoral and radial waveforms are not interchangeable , 18. TreAs outlined earlier, the minimally invasive pulse contour analyses systems must convert a pressure measurement into a volume parameter. Since it is impossible to non-invasively measure the determinants needed for this transformation, this transformation is prone to error, especially during some underlying pathologies.As data show, agreement of the minimal-invasive methods with reference methods is poor, especially in patients during low SVR states such as sepsis and chronic liver failure –22. AppaThe MostCare™ system that derives the arterial impedance from the pressure waveform itself and not from an internal nomogram overestimates CO in low SVR states , but datThe manufacturer of the LiDCOrapid™ system does not recommend its use during peripheral vasoconstriction.Due to the altered arterial waveform during intra-aortic balloon-pump therapy, most systems cannot identify the systolic and diastolic portion of the waveform correctly. Therefore, these systems are not able to display correct values. The use of the LiDCOrapid™, Vigileo™, and Pulsioflex™ systems is not recommended by the manufacturers. For the MostCare™ system, a study with 15 patients could show a good accuracy in patients with IABP, probably due to its different approach to measurements .The accuracy and trending ability are used for the evaluation of the pulse contour analysis systems. While accuracy is the agreement with an absolute value of a reference method, trending ability indicates the extent to which a change in CO over time is correctly estimated. As described earlier, none of the methods perform a measurement. Since the CO is only estimated according to different algorithms, the pulse contour analysis methods are error prone when used in critically ill patients who often have a low SVR, i.e., in septic shock as outlined earlier.The Vigileo/FloTrac™ algorithm has been refined several times, and the manufacturer claimed an improvement in accuracy and trending ability with each iteration of the software. However, the available validation studies for the up to date fourth generation software could not show a sufficient accuracy or trending ability for this system when used in patients with changes in SVR or with low CO, although the performance has improved over the previous software versions –29. ConcIn summary, none of the systems has a sufficient accuracy to be used in critically ill patients. Nevertheless, it must be noted that despite the inability to correctly estimate CO, it has been shown that these systems may improve outcome when used intraoperatively and algorithm based –39, althTherefore, it is important that the pulse contour methods are used in a targeted manner in selected patients, where a benefit for their application could be shown. In critically ill patients or if accuracy plays a role, transpulmonary or pulmonary artery thermodilution methods should be used.Uncalibrated PCS are less-invasive methods to estimate CO. Only a conventional arterial catheter that is present in many critically ill patients is required. For the transformation of the arterial waveform as a pressure signal to CO, assumptions on the dynamic characteristics of the arterial vasculature must be made. Most systems use internal databases or nomograms based on demographics, while one system uses a complex calculation to estimate the necessary parameters.Special attention has to be given to the arterial waveform as the input signal of the pulse contour monitors. Neither over- nor under-dampened signals are suitable for analysis and regularly require the operator’s intervention for the assessment of the dynamic response characteristics of the catheter–transducer system, i.e., by a fast-flush test. The operator must confirm that the waveform is correct before obtaining CO values from the monitor.The use of PCS is limited in patients with large deviations from normal SVR or in patients receiving intra-aortic balloon pumps. The accuracy and trending ability of the CO estimation compared with thermodilution measurements is often limited. However, it has been shown that an algorithm-based use of PCS can improve the perioperative outcome of patients. Uncalibrated PCS represent a helpful, less-invasive tool in the hemodynamic armamentarium of the critical care physician.The author listed has made a substantial, direct, and intellectual contribution to the work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Postural hypotension, as a manifestation of autonomic neuropathy is a very sinister long-term debilitating complication of diabetes, is usually irreversible and tough to manage with medications. The treatment of this condition following the standard treatment protocols can be contraindicated in the patients with underlying heart conditions. We report the case of a patient at our hospital who presented with full-blown symptomatic dysautonomia secondary to long-standing diabetes, with bedside testing positive for autonomic dysfunction. Treating this patient with the standard protocol of adrenergic agonist could have worsened his underlying coronary artery disease. So, we moved a step aside to go out of the box and we have a trial of the β1-selective beta-blocker, with astonishing results and significant improvement in the quality of life and symptoms of postural hypotension. We report here the use of alternative treatment option in managing a patient with severe postural hypotension secondary to diabetes-related autonomic neuropathy when adrenergic drugs are contraindicated. Orthostatic hypotension is the core feature of autonomic failure. Orthostatic hypotension is defined as a fall in the blood pressure of 20/10 mmHg on standing for three minutes. This definition is meant to capture the initial or mild cases. The symptomatic orthostatic hypotension is more commonly encountered in the subjects with falls in blood pressure that may range from this figure to the severe cases where the fall in the blood pressure may be 100/50 mmHg. The most common symptoms of orthostatic hypotension are lightheadedness, mining of vision, and discomfort in the head , neck, shoulders, and sometimes the chest. Orthostatic hypotension is the most bothering symptom, often complained by the patients suffering from diabetic neuropathy [Diabetic neuropathy can be asymptomatic or can be a cause of significant disability. Any or all the organs innervated by the autonomic system can be affected by diabetes. The symptoms can arise from the involvement of a single system or multiple systems and can range from postural hypotension, diarrhea, gastroparesis, overflow urinary incontinence, impotence to dry skin and gustatory sweating . Commonl1) Beat-to-beat cardiac variation with position or respiration2) Valsalva ratio  ratio > 1.2)3) Heart rate response to deep breathing 4) Ratio being 30:15 R-R Interval ratio (30th to 15th R-R ratio on standing > 1.03)5) Fall in the blood pressure of 20/10 mmHg on standing for three minutes.Diabetic autonomic neuropathy often goes unrecognized and it remains asymptomatic most of the time, but often it presents with debilitating symptoms. We present a case of 48-year-old male with the history of a type-II diabetic for 20 years and coronary artery disease (CAD). The patient had poor control of diabetes and had diabetic complications of gastroparesis, retinopathy, nephropathy, neuropathy, and CAD. The presenting complaints were dizziness for two months with the progressive inability to stand without support. On examination, he was a lethargic middle-aged man lying comfortably in bed. The lying blood pressure (BP) was 150/90 mmHg with the significant postural drop measuring up to 80/60 mmHg after two minutes of standing. The neurological exam of diabetes showed distal symmetric sensory neuropathy to light touch, while the vibration sensation and proprioception were intact. The fundoscopy revealed scattered hard exudates, dot, and blot hemorrhages. He was never tested for autonomic dysfunction prior to this encounter and did not take any medication, since midodrine was not available in Pakistan and fludrocortisone was never prescribed by the general practitioner, due to the lack of complete testing and affordability issues.Electrocardiography findings suggestive of dysautonomia were:1) Abnormal heart rate response to deep breathing was 1.0 2) The abnormal Valsalva ratio was 1.03 3) Abnormal 30:15 R-R interval ratio was 0.99 .These three tests along with the significant postural drop were suggestive of marked cardiac dysautonomia in this patient. The lab data showed the complete blood count, serum electrolyte test, renal function tests, liver function tests, serum cortisol, Adrenocorticotropic hormone (ACTH) and the thyroid function tests as normal. Midodrine, in this patient, could not be used because of the history of the significant CAD. The patient did not have any response to fludrocortisone. So as a final resort, he was started on atenolol P.O. . The patient had dramatic clinical improvement with this therapy. The orthostatic blood pressure changes improved and he was able to ambulate without any difficulty.Diabetic autonomic neuropathy is the impairment of autonomic control in the setting of diabetes after exclusion of other causes. Ewing, et al. recommend five simple tests, the cardiac autonomic reflex tests to establish the diagnosis: 1) Heart rate variability (HRV) with deep breathing; 2) the HRV lying to standing; 3) the Valsalva maneuver; 4) postural fall in the blood pressure; and 5) the blood pressure response to sustained handgrip [Drugs used for the treatment of postural hypotensionFludrocortisoneFludrocortisone is a mineralocorticoid, which causes sodium retention and enhances the sensitivity of the blood vessels to circulating catecholamine .MidodrineMidodrine is a prodrug that acts by stimulating the alpha-1 adrenoreceptors to constrict the blood vessels and raise the blood pressure . The preEven though adrenergic drugs like midodrine are the first line choice in the patients with orthostatic hypotension from diabetic autonomic neuropathy, their use is limited in the patients with contraindications.The standard protocol of treating diabetic autonomic neuropathy related postural hypotension recommends using fludrocortisones and midodrine, however, our patient was having coronary artery disease, so the use of adrenergic agonist was just synonymous to relieving one debilitating symptom and putting him into another life-threatening state. The studies have shown that the beta-adrenergic blockers do not cause orthostatic hypotension . A cardiNonselective β-blockers with intrinsic sympathomimetic activity and the β1 selective agents with no intrinsic sympathomimetic activity like atenolol have been used in several trials in the treatment of orthostatic hypotension and for the prevention of presyncope with variable results . The sugA similar case was reported in the Journal of Human Hypertension in 2006. A 54-year-old male with diabetes was referred to the hypertension clinic in the Jichi Medical School Hospital with symptoms of dizziness and orthostatic intolerance and was successfully treated with the β1-blocker .The β1- selective blocker (atenolol) effectively reduced the orthostatic blood pressure changes in this patient with severe orthostatic hypotension due to diabetic autonomic neuropathy and the main finding was an improvement of the elevated supine blood pressure without reducing the standing blood pressure. According to the author, this differential antihypertensive effect is ideal for the medication in orthostatic hypotension, but the authors found it to be very different from other case reports, of the effects of the β-blockers, where the emphasis has been on increasing the standing pressure. They claim that the study was unique in two ways: 1) the use of 24-hr ambulatory monitoring and 2) they describe a potentially different mechanism whereby the β-blockers may benefit the patients with orthostatic hypotension.Postural hypotension, as part of the spectrum of diabetic autonomic dysfunction, can be difficult to manage in conditions where adrenergic drugs are contraindicated. Our case report highlighted the importance of the beta blockers for the treatment of postural hypotension in special circumstances. Increased awareness and effective monitoring of diabetic autonomic neuropathy can help decrease the morbidity associated with it. Further studies are needed to address this cumbersome condition.


P=0.95/0.48, plasma renin activity (PRA) (ng/ml·h): 2.41±2.67 compared with 2.00±1.50 P=0.20, PAC (pg/ml): 77.3±31.0 compared with 67.4±24.8, P<0.05, urinary albumin excretion (UAE) (mg/gCr): 105.9±216.1 compared with 73.9±122.2, P<0.05. Thus, PAC at cilnidipine was significantly lower than those at amlodipine in spite of the comparable BP reductions. Besides, UAE was significantly lower at cilnidipine. In conclusion, on the top of the ARB, it is suggested that cilnidipine administration might lead to less elevation of PAC and reduction in UAE compared with amlodipine.The activation of the renin–angiotensin system (RAS) is one of the unfavourable characteristics of calcium channel blocker (CCB). N type calcium channel is thought to be involved in renin gene transcription and adrenal aldosterone release. Accordingly, N/L type CCB has a possibility of less elevation of plasma aldosterone concentrations (PAC) among CCBs. In a monotherapy study, we had already demonstrated that N/L type CCB leads to less activation of the RAS compared with L type CCB. The objective of this study is to substantiate the hypothesis that at the condition of additive administration on the top of an angiotensin receptor blocker (ARB), still N/L type CCB leads to less elevation of PAC compared with L type one. Subjects were 60 hypertensives administered with valsartan. As an open label study, amlodipine (L type) or cilnidipine (N/L type) were administered on the top of valsartan (ARB) in a cross-over manner. Results were as follows : systolic blood pressure (SBP)/diastolic blood pressure (DBP) (mmHg): 132±10/76±10 compared with 131±10/77±9,  Calcium channel blocker (CCB) is one of the most useful anti-hypertensive agents in respect of sure anti-hypertensive effect and no crucial adverse effect. However, the activation of the renin–angiotensin system (RAS) is one of the unfavourable characteristics of CCB in a stand point of organ protection, because the RAS plays major roles in blood pressure (BP) regulation and electrolyte metabolism , at the Recently, for the organ-protective hypertension therapy, angiotensin receptor blocker (ARB) is often selected as the first line agent and CCB is added as a complementary agent. Thus it should be a clinically important issue whether the RAS activation and UAE levels are different among L type CCB and N/L type CCB. Thereby, we substantiated the hypothesis whether at the condition of additive administration on the top of an ARB, still N/L type CCB leads to less activation of the RAS, especially plasma aldosterone concentrations (PAC) compared with L type CCB.Subjects were recruited from 2007 January to 2013 September. Subjects with age less than 20 years old, secondary hypertension, acute phase disorder and severe organ failure were excluded. We had assessed for eligibility for the study on 68 subjects, who did not obtain the targeted BP  by valsartan alone and enrolled 60 consecutive hypertensives administered with valsartan of our out clinic into the study. All subjects were Japanese. At the out clinic in the morning time, on each occasion, BP was taken at least three readings with an automated digital device  at sitting position. If readings varied more than 5 mmHg, additional readings were taken until the last two were close with in the 5 mmHg according to general guidelines for hypertension care. BP measurements were tried to be performed in the same way every visit. The body mass index (BMI) was calculated as the weight in kilograms divided by the square of the height in meters. Metabolic syndrome was diagnosed according to the criteria of the Japan atherosclerosis society. Diabetes mellitus (DM) was diagnosed according to the criteria of the World Health Organization. Dyslipidaemia was diagnosed according to the criteria of the International Diabetes Federation. Chronic kidney disease (CKD) was diagnosed according to the criteria of the Japanese society of nephrology. Diabetic subjects, 53.3% of the total subjects, continued to receive their usual care for diabetes. A target glycated haemoglobin level of less than 7.0% was recommended for all subjects. Arterial hypertension was defined as a systolic blood pressure (SBP) of 140 mmHg or more or a diastolic blood pressure (DBP) of 90 mmHg or more on two separate occasions. The study was undertaken in accordance with the Declaration of Helsinki Principles and informed consent for participation was obtained from individuals. The clinical characteristics at valsartan administration were summarized in 2)=194 × Cr−1.094 × Age−0.287 . After 15 min rest in the supine position, blood samples were drawn for the measurement at our out clinic in the morning. Ideally sampling should be done on the same time of the day for RAS components measurements. However, there was a limit for actual practice on out clinic. For avoiding cold activation and degradation of humoral factors, the plasma samples were frozen as soon as possible. For plasma renin activity (PRA) measurement sample were incubated 37°C for adequate hours and generated angiotensin I was measured by radioimmunoassay . PAC and atrial natriuretic peptide (ANP) were assayed by radioimmunoassay . Urinary albumin excretion (UAE) was measured by immunoturbidimetry .As an open label study, on the top of valsartan (ARB) administration, the additive amlodipine (L type CCB) or cilnidipine (N/L type CCB) was administered for 12 weeks each in a cross-over manner by randomized turn with a table as a combination therapy without washout periods . Amlodipt test with protection against type I error of 5% and 80% of power. From Altman's nomogram with 2δ/σd value for paired t test, it was calculated tentatively the study required around 50 subjects in total. Statistical analyses were performed with SPSS Version 22.0 (SPSS Japan). Data were presented as numbers, percentages, means±S.D. or medians (interquartile ranges), as appropriate. The differences between two paired continuous variables were analysed by Student's t test fundamentally or Wilcoxon signed rank test appropriately. The difference in PAC and UAE were analysed by repeated measures ANOVA.The sample size of the study was calculated estimating a standard deviation for the PAC of about 25; a difference to be detected between groups of 10 pg/ml and used a bilateral paired Student's Final doses of amlodipine besilate and cilnidipine were 6.0±2.6 mg/day and 13.0±4.8 mg/day, respectively. On the top of valsartan, a total number of 60 subjects received combination therapy with amlodipine or cilnidipine by turns in a cross-over manner for 12 weeks each, so that the study lasted 24 weeks totally. No serious adverse effect occurred in the study term. Changes in clinical and biochemical characteristics with drugs administration are summarized in At the original baseline, which means the state just before the beginning of anti-hypertensive therapy with valsartan as a representative ARB, BP revealed to be 162±18/93±12 mmHg, retrospectively. With valsartan administration, BP had been significantly reduced to 145±16/87±10. PRA had been significantly augmented from 0.64±0.56 to 1.50±2.14. PAC had been significantly reduced from 78.9±34.6 to 63.1±31.9 . UAE hadWith both of CCBs administration, significant reductions in systolic and diastolic BP were achieved from the state of valsartan monotherapy . The BP Recent studies of the human renin revealed the transcriptional mechanism –7, the gP=0.485, Wilcoxon's signed rank test), angiotensin II: 11.5  at amlodipine and 10.5  at cilnidipine . Thus, the results did not reached a statistical significance but a tendency was shown that components of RAS were less activated at cilnidipine indicating that low tendency of PRA might effect on the lower stream of the system cascade. Accordingly, it seems that not only the release of aldosterone from adrenal cortex but also lower PRA partly might contribute to the results.In recent guidelines, ARB is recommended for complicated hypertensives such as DM and CKD. However, in many cases, single ARB therapy is not sufficient. Thus the additional agents are required such as CCB. On the other hand, the variation in PAC levels is shown to be associated with increased mortality independent of major established cardiovascular disease (CVD) risk factors  and aldoIt has been revealed that UAE is a risk factor for end stage renal disease and CVDs ,27. BesiSeveral limitations of this study should be noted. Mixture of non-diabetic and diabetic subjects might have effects on the results. We did not evaluate ambulatory BP results compared with office BP. Considering the earnest practical limit for clinical human subjects in Japan, washout period between the two drugs administration was not set up. The sample number may be still relatively small. Although primary endpoint of the study was changes in PAC from the state of single valsartan administration, we used multiple statistical comparisons. The change in eGFR could be more precise surrogate as well as albuminuria; however, the observation period was not sufficient for its evaluation.In conclusion, it is suggested that cilnidipine might lead to less elevation of plasma aldosterone level compared with amlodipine for the first time in human clinical study as the primary end point with anti-albuminuric effect. Further investigations should be necessary for evaluation for hard end points.