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The relation between glucose homeostasis and cerebral blood flow (CBF) and their correlation to outcome in neonatal hypoxic-ischemic encephalopathy are unclear. In this short communication, we tried to determine whether changes in regional oxygen saturation (rSO2), as measured by near-infrared spectroscopy (NIRS), in asphyxiated neonates during therapeutic hypothermia correlate with the glycemic profile and whether NIRS and continuous glucose monitoring are useful in identifying cooled asphyxiated neonates at high risk of brain injury. Although there was no correlation between blood glucose and CBF in this small cohort of asphyxiated neonates (13 neonates admitted to the IRCCS Giannina Gaslini NICU in Genoa between March and September 2021), after 24 h of life, increased rSO 2 and glucose variability with a tendency toward hyperglycemia distinguished neonates who subsequently acquired brain injury from those who did not. As a result of this, it may be possible to monitor cerebral perfusion and metabolic changes as soon as possible after delivery in order to prevent poorer outcomes., Competing Interests: No competing financial interests exist., (© Giulia Vagelli et al., 2024; Published by Mary Ann Liebert, Inc.)

Competing Interests: Declaration of Competing Interest None.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-628). Dr. Bertamino reports grants from Compagnia San Paolo, during the conduct of the study. All 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.

Conjugation of known biologically active molecules to carbohydrate frameworks represents a valuable option for the preparation of hybrid, structurally-related families of compounds with the aim of modulating their biological response. Therefore, we present here a study on the preparation of d- galacto , d- manno , d- gluco , and d- lactose glycoconjugates of an established N -hydroxyindole-based (NHI) inhibitor of lactated dehydrogenase (LDH). Structural variations involved the sugar stereochemistry and size as well as the anchoring point of the NHI on the carbohydrate frame (either C-1 or C-6). In the case of the galactose anomeric glycoconjugate (C-1), intriguing solvent-dependent effects were observed in the glycosylation stereochemical outcome. The biological activity of the deprotected glycoconjugates in contrasting lactate formation and cancer cell proliferation are described.

Background: The assessment of the early motor repertoire is a widely used method for assessing the infant's neurological status., Aim: To determine the association between the early motor repertoire and language development., Study Design: Prospective cohort study., Subjects: 22 term children born after normal pregnancy; video recorded for the assessment of the early motor repertoire including their motor optimality score (MOS), according to Prechtl, at 3 and 5months post term., Outcome Measures: At 4years 7months and 10years 5months, we tested the children's language performance by administering three tests for expressive language and two for receptive language., Results: Smooth and fluent movements at 3months of age was associated with better expressive language outcome at both 4years 7months and 10years 5months (betas 0.363 and 0.628). A higher MOS at 5months was associated with better expressive language at both ages (betas 0.486 and 0.628). The item postural patterns at 5months was the only aspect associated with poorer expressive language outcome (beta -0.677)., Conclusion: Predominantly, qualitative aspects of the early motor repertoire at the age of 3 and 5months are associated with language development., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In 2010 a questionnaire was administered to the renal units of Piedmont and Valle d'Aosta to analyze their procedures for renal biopsy (RB). Seventy-eight percent of units performed RBs, 57% for more than 20 years, but only 43% performed at least 20 BRs per year. 20/21 units performed RB in an inpatient setting and 1/21 in day hospital with the patient remaining under observation the night after. Thirty-two percent did not consider a single kidney as a contraindication to RB, 59% considered it a relative contraindication and 9% considered it an absolute contraindication. In 90.5% of units there was a specific protocol for patient preparation for RB and 86% used a specific informed consent form. Ninety-five percent of units performed ultrasound-guided RB, 60% of them using needle guides attached to the probe. In 81% of units the left side was preferred; 71% put a pillow under the patient's abdomen. All units used disposable, automated or semi-automated needles. Needle size was 16G in 29%, 18G in 58%, and both 16G and 18G in 14% of units; 1 to 3 samples were drawn. One third of units had a microscope available for immediate evaluation of specimen adequacy. After RB, 86% of units kept patients in the prone position for 2-6 hours and all prescribed a period of bed rest (at least 24 hours in 90.5%). 90.5% of units followed a specific postbiopsy observation protocol consisting of blood pressure, heart rate and red blood cell measurements at different times, and urine monitoring and ultrasound control within 12-24 hours (only half of them also employing color Doppler). One third of all units discharged patients after 1 day and two thirds after 2-3 days; all prescribed abstention from effort and from antiplatelet drugs for 7-15 days. In 9 units both RB and tissue processing and examination were done in the same hospital, while 12 units sent the samples elsewhere. 76% obtained results in 2-4 days, 19% in 6-7 days, and 5% in 10-15 days. Less than 20% of the interviewed operators were fully familiar with the clauses of hospital insurance securing their activity. Use of RB is widespread in Piedmont and Valle d'Aosta but its practice shows variation between centers.

The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.

This article describes the effects of surface controlled decarburization on the structure of a nitrided steel. Samples of quenched and tempered 40CrMo4 steel were decarburized by air heat treatment (800-900 degrees C) at different depths and submitted to gaseous nitriding. The microstructure of surface layers after decarburization and nitriding were investigated by optical (OM) and scanning electron microscopy (SEM). The nitrogen and carbon profiles in the diffusion layers were determined by a scanning electron microscope equipped with a wavelength dispersive spectrometer (EPMA-WDS). The effect of nitriding was determined by microhardness measurements. The increasing of time and temperature of decarburization slightly affect the surface hardness values, while case hardness depths decrease. In all the specimens, the nitriding depth, as determined by the WDS nitrogen profile, is larger than the one determined by the hardness profile.

Purpose: In renal disease therapy (RDT) patients, high plasma homocysteine (tHcy) is common and high C-reactive protein(CRP) levels can be observed, attributed to the inflammatory process caused by the dialysis itself. Hyperhomocysteinemia and bioincompatibility are considered independent vascular risk factors. This study evaluated the behavior of these parameters in patients undergoing on-line hemodiafiltration (OL-HDF)., Methods: In 56 patients, HDF was performed using high permeability polyamide membranes, exchanging in the post-dilution mode 16-18 L/session of a reinfusate obtained by the on-line system (triple filtration AK200, Gambro). CRP was measured by an immunological method at the start and the end of the session in patients without comorbidities (group 1, n=30)and with inflammatory diseases (group 2, n=26). In 23 of the 56 patients, tHCY was measured (by high performance liquid chromatography (HPLC)) before and after the mid-week session on different schedule of folinic acid, vitamin B12 and vitamin B6., Results: Pre-dialytic CRP was in the normal range in group 1 patients, whereas it was higher in group 2 patients; dialysis did not induce a significant change in either group. The intradialytic percentage tHcy decrease was approximately 50% regardless of the pre-dialytic value, which was significantly different according to the vitamin supplements administered., Conclusions: HDF, as performed in this study, demonstrated biocompatibility and efficient Hcy removal; therefore, it can prevent cardiovascular disease (CVD) in patients on regular extracorporeal dialysis.

Background: High total homocysteinemia (tHcy) is a vascular risk factor in regular dialysis treatment (RDT) patients. A near normal tHcy has previously been achieved (from 33 +/- 11 to 13 +/- 5 micromol/L) in 23 patients on hemodiafiltration (HDF) by adjusting intravenous (i.v.) supplements of folinic acid, vitamin B12 and B6, gradually during a 2-yr follow-up. Thereafter, the same therapeutic schedule was used for all patients undergoing RDT in our unit to confirm its efficacy on a larger scale., Patients and Methods: Patients (n=63, F 34, age 66 +/- 14 yrs, dialytic age 60 +/- 53 months) underwent high UF post-dilutional on-line HDF for at least 6 months. They received i.v. folinic acid 3 mg, vitamin B12 50 microg and vitamin B6 450 mg/wkly. After 4 months, pre- and post-dialytic serum Hcy (n.v. 11 +/- 2 micromol/L), as well as pre-dialytic serum folate (sFA, n.v. 3-17 ng/mL) and vitamin B12 (sB12, n.v. 226-966 pg/mL) were determined., Results: The mean pre-dialytic tHcy fell to within the normal range (from 31 +/- 10 to 12.5 +/- 5 umol/L), it was slightly above the normal limits (19 +/- 2 umol/L) in only 11 patients (17%), whereas the post-dialytic value was normal in all patients (7 +/- 2.5 umol/L). The average values of sFA (25 +/- 10 ng/mL) and sB12 (1500 +/- 320 pg/mL) were approximately twice the normal limits., Conclusion: Therefore, HDF appears to remove tHcy efficiently and tHcy is generally normalized by adjusting the dose of vitamin B12, vitamin B6 and folinic acid supplements.

Background: We tested whether the combination of verapamil (V) or amlodipine (A) with trandolapril (T) affected proteinuria differently from T alone in patients with nondiabetic nephropathies., Methods: After T, 2 mg, in open conditions for 1 month, 69 patients were randomly assigned to be administered T, 2 mg, combined with V, 180 mg, plus a placebo or T, 2 mg, plus A, 5 mg, once a day in a double-blind fashion. Patients were followed up for 8 months., Results: Proteinuria diminished significantly after T treatment from mean protein excretion of 3,078 +/- 244 (SEM) to 2,537 +/- 204 mg/24 h (P = 0.018). In the randomized phase, there was a slight reduction in proteinuria in both groups without significant differences within and between treatments (T + V, protein from 2,335 +/- 233 to 2,124 +/- 247 mg/24 h; T + A, protein from 2,715 +/- 325 to 2,671 +/- 469 mg/24 h). The selectivity index (SI; calculated as the ratio of immunoglobulin G to albumin clearance) was slightly and not significantly reduced in patients treated with T plus V from a median of 0.20 (interquartile range, 0.13) to 0.16 (interquartile range, 0.15; P = not significant), whereas it significantly increased from 0.20 (interquartile range, 0.14) to 0.30 (interquartile range, 0.14; P = 0.0001) in patients treated with T plus A. Modifications in SI and serum creatinine levels at the end of the study from randomization were significantly directly correlated (r = 0.45; P = 0.001). The number of patients reporting adverse effects was significantly higher in the T plus A than T plus V group (63.8% versus 33.3%; P = 0.016)., Conclusion: In patients with nondiabetic proteinuric nephropathies treated with T, the combination of V or A does not significantly increase its antiproteinuric effect.

The study evaluates the potential of high ultrafiltration on-line hemodialfiltration (HDF) as a means of achieving the goals of extracorporeal RDT: the removal of small and medium-sized molecules, vascular stability and biocompatibility. The removal of small molecules was correlated with the UF rate and therefore with reinfusate volume. Medium-sized molecules were only removed from high permeability synthetic membranes in HD, but to a greater extent in HDF because of higher absorption. Vascular stability during the dialytic session is improved by convective processes, as is confirmed by a low prevalence of arterial hypertension in HDF patients. This suggests that HDF facilitates the achievement of dry body weight and therefore an improved correction of hydrosaline retention which is the main cause of hypertension in RDT patients. The biocompatibility of the dialytic system depends on the membrane and the dialysate. Synthetic membranes were shown to be much less toxic than cellulosic membranes and ultrapure dialysate was a useful aid to reduce the risk of inflammatory stimuli. On-line HDF associated the value of low-cost sterile dialysate-reinfu sate with a highly efficient and well tolerated technique.

Angiotensin converting enzyme inhibitors (ACEI) are the most effective antiproteinuric agents and should be used as first-line drugs in both diabetic and non-diabetic proteinuric nephropathies. The role of calcium channel blockers (CCB) is much more controversial. In diabetic patients verapamil and diltiazem seem more effective than dihydropyridines in reducing urinary protein excretion, and have additive effects with ACEI, but little is available on chronic treatment of non-diabetic nephropathies for non-dihydropyridine CCBs. To test whether the combination of verapamil 180 mg or amlodipine 5 mg with trandolapril 2 mg reduces urinary protein excretion more than trandolapril 2 mg alone, we planned a prospective, randomized, double-blind, multicenter trial. The secondary aims are to evaluate the effects of both treatments on the selectivity of proteinuria and check their safety. Consecutive patients aged between 18 and 70 years with non-diabetic proteinuria > or =2 g/24 h and plasma creatinine < 3 mg/dl or creatinine clearance > or = 20 ml/min are asked to participate. After a four-week run-in during which previous antihypertensive therapy is withdrawn, a single dose of trandolapril 2 mg is given once a day in open conditions for four weeks. At the end of this period patients are randomly assigned to receive once a day, in a double blind fashion, either trandolapril 2 mg and verapamil 180 mg [plus a placebo], or trandolapril 2 mg plus amlodipine 5 mg. They are monitored after one, two, five and eight months.

Background: While in vitro the protective effect of magnesium on calcium oxalate crystallization is well known, its clinical relevance in calcium nephrolithiasis is still debated. Therefore, the clinical and metabolic effects of magnesium hydroxide therapy were evaluated in calcium stone formers., Methods: Nine patients (7 M, 2 F), selected for a low urinary magnesium excretion (uMg 56 +/- 12 mg/day), were given Mg hydroxide (500 mg/day), with clinical and metabolic controls at 3, 12 and 18 months., Results: Urinary Mg/uCreat increased throughout the study; uOx/uCreat decreased significantly; uCa/uCreat increased but not significantly. The stone recurrence rate decreased from 0.75 to 0.11 stones/year/patient, throughout the study period. The decrease of uOx is considered a more important risk factor in calcium stone patients than a similar uCa change; it may be due to a reduced intestinal Ox absorption, for the formation of insoluble and not absorbed Mg oxalate., Conclusion: In conclusion, Mg hydroxide therapy was encouraging in patients with calcium nephrolithiasis and low uMg; nevertheless a longer period of treatment is needed to confirm these data.

In the attempt to prevent malnutrition, a seven year longitudinal evaluation was carried out in 24 RDT patients in order to assess the efficacy of the following strategy: 1) Counseling for an adequate physical activity and a high caloric intake limiting dietary restrictions to fluids, salt and fruit. 2) Improvement of anemia by increasing dialysis dose and/or by administering EPO. 3) The use of high UF HDF in order to employ more biocompatible membranes and to improve small and middle molecules removal. Nutritional status was assessed by a biochemical screening and by evaluating the variations of dry body weight (BW), which had to be also confirmed by a normal cardiac volume. Moreover in all patients a 4 consecutive days dietary record was obtained one year before the end of the observation period. During this period the mean dry BW increased significantly except in the two last years, when it remained stable. The increase of BW was associated with a reduced incidence of hypertension, a significant increase of Hb and reduction of BUN and sCr. The remaining biochemical parameters were constantly in the normal range. The dietary record showed a mean caloric-proteic intake similar to that recommended for the general population. These data point out that the above strategy can prevent malnutrition in patients on RDT. It must be confirmed whether the use of more biocompatible membranes and the removal of the middle molecules can play an important role in this setting.

Hypertension and calcium nephrolithiasis show some common features, such as the high prevalence of hypercalciuria and of elevated urinary sodium excretion. 28 patients with idiopathic calcium stone disease and 17 normals were studied: all the subjects were evaluated for the mean arterial pressure, and for the metabolic risk factors for calcium stone disease. The mean arterial pressure proved to be higher in patients with calcium nephrolithiasis than in normals. In normals the mean arterial pressure showed a direct relationship with the urinary calcium, while in the group of stone patients it had a direct relationship with the urinary sodium excretion. The lack of relationship between the mean arterial pressure and calcium excretion, in patients with calcium stones, suggests an impaired tubular calcium handling in such patients.

Electrolyte and acid-base balance was evaluated in 14 high UF (124 +/- 7 ml/min) hemodiafiltration sessions. The dialysate contained (in mEq/l): Na 138-140, K 2-3, Ca 3.5, Mg 0.5-0.7, Cl 106-110, acetate 38 or acetate 3 and bicarbonate 35-38. The fluid, infused in postdilutional mode, was 23.5 +/- 21 per session (session length 203 +/- 22 minuti), 80% containing Na 138, K 2, Ca 3.5, Mg 1, Cl 109.5, acetate 35 and 20% Na 145, HCO3 100, Cl 45. The balance was: negative for Na (-255 +/- 220 mEq), for K (-74 +/- 22 mEq) and for Mg (-166 +/- 141 mg), positive for Ca (215 +/- 147 mg) and for acetate (590 +/- 15 and 966 +/- 412 mmol); the electrolytes and bicarbonate plasma values were within of close to normal limits during the session. An unphysiological feature was the positive balance of acetate which, though, was metabolized during the interdialytic period as to return to normal predialytic values. Therefore, in high UF HDF, the above combination of dialysate and reinfusate allows a reasonable electrolyte and acid-base balance; however, bicarbonate should be the only buffer in order to avoid unphysiological levels of other buffers in the biological fluids.

A group of well nourished young patients was examined during 2 longterm consecutive high efficiency dialytic schedules to detect possible clinical and biochemical differences. The patients were first studied during hemodialysis with a 1.2 m2 cuprophan membrane and blood flow of 400 ml/min and, then, during hemodiafiltration with an ultrafiltration rate greater than 100 ml/min by using high permeability membranes with a surface greater than or equal to 1.4 m2. As expected by the higher clearances obtained on hemodiafiltration, this technique resulted in a significant reduction of dialysis time and of BUN and serum creatinine, associated with a significant increase of hemoglobin, possibly related to a better deintoxication. Furthermore, the dry body weight decreased significantly during hemodialysis, whereas it increased significantly during hemodiafiltration, despite unchanged dietary habits, indicating possible differences in the nutrients utilization during the 2 dialytic schedules. Therefore, in chronically dialyzed patients, highly permeable synthetic membranes should be preferred to cuprophan because of a supposed better biocompatibility and should be used with the highest ultrafiltration rate in order to obtain a better dialytic efficiency and to avoid the risk of backfiltration.

The effect of high doses of CaCO3 on serum phosphorus and calcium (sPi,sCa) and the changes in serum aluminum (sAl) induced by Al(OH)3 interruption were investigated in patients on regular hemodialysis treatment. Some patients were administered Al(OH)3 and CaCO3, others only the former or the latter and others nothing. Al(OH)3 was stopped in all but one in whom it was only reduced, and CaCO3 was started or increased in all patients. A better control of sPi and serum Ca-Pi product was observed during high Ca supplementation, despite Al(OH)3 discontinuation, and was associated with a significant decrease of sAl. As expected, taking into account the dialysate Ca level of 4 mEq/l, a significant hypercalcemia occurred in some patients, especially in those who had a normal predialytic sPi without Al(OH)3 supplementation. Therefore, lowering the dialysate Ca concentration according to individual need and increasing interdialytic oral Ca supplements can be recommended with the dual purpose of keeping a positive Ca balance and correcting hyperphosphatemia.