Monitoring and management of hyperglycemia in patients with advanced diabetic kidney disease

Diabetes mellitus is the leading cause of end-stage renal disease, and uncontrolled hyperglycemia is directly related to the increased mortality in this setting. As kidney function decreases, it becomes more challenging to control blood glucose since the risk of hypoglycemia increases. Decreased appetite, changes in glycaemia homeostasis, along with reduced renal excretion of anti-hyperglycemic drugs tend to facilitate the occurrence of hypoglycemia, despite the paradoxical occurrence of insulin resistance in advanced kidney disease. Thus, in patients using insulin and/or oral anti-hyperglycemic agents, dynamic adjustments with drug dose reduction or drug switching are often necessary. Furthermore, in addition to consider these pharmacokinetics alterations, it is of utmost importance to choose drugs with proven cardio-renal benefits in this setting, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists. In this review, we summarize the indications and contraindications, titration of doses and side effects of the available anti-hyperglycemic agents in the presence of advanced diabetic kidney disease (DKD) and dialysis, highlighting the risks and benefits of the different agents. Additionally, basic renal function assessment and monitoring of glycemic control in DKD will be evaluated in order to guide the use of drugs and define the glycemic targets to be achieved.     

A new biliary access technique for the long-term endoscopic management of intrahepatic stones

Intrahepatic stone disease poses a difficult postoperative management problem due to frequent stone recurrence. Most of the methods proposed for long-term access to the intrahepatic biliary tree require multiple sessions of additional, usually invasive, procedures. An alternative method for endoscopic long-term access to the intrahepatic ducts, represented by a side-to-side anastomosis between the isolated Roux-en-Y jejunal limb of the bilioenteric bypass and the duodenum (duodenojejunostomy), was used in eight patients with retained and/or recurrent stones after surgical treatment of intrahepatic stone disease. There were no short- or long-term complications or mortality associated with the duodenojejunostomy. Postoperative endoscopic access to the intrahepatic ducts was successfully achieved in five of six patients: one with stone recurrence, one with a left hepatic duct stricture and stone recurrence and one with known retained postoperative stones. In two patients, no stones were found at endoscopy. Side-to-side duodenojejunostomy may be useful in the long-term endoscopic management of recurrent intrahepatic biliary stone disease and should be indicated whenever a bilioenteric anastomosis is performed for the treatment of bilateral intrahepatic stone disease. Introduction     

The cerebrospinal fluid/serum leptin ratio during pharmacological therapy for obesity

The aim of the present study was to evaluate the cerebrospinal fluid (CSF)/serum leptin ratio during pharmacological therapy for obesity with centrally and peripherally acting drugs. Thirty-one obese women (mean age, 32.3 +/- 10 yr; body mass index, 38.2 +/- 5.2 kg/m(2); body fat, 43.3 +/- 5.4%) were studied before and 2 months after a weight loss program consisting of a balanced diet (1200 kcal/d) plus drug therapy. The patients were randomly assigned into three study groups: group I, fenproporex 25 mg/d (n = 10); group II, sibutramine 10 mg/d (n = 10); and group III, orlistat 120 mg tid (n = 11). Body fat, measured by dual-energy x-ray absorptiometry, and serum and CSF concentrations of leptin were examined at baseline and 2 months after therapy. At baseline, clinical and biochemical characteristics of the groups were similar. All of the women lost weight, approximately 7.0% of their initial body weight, and the reduction was not different among the groups. Serum leptin fell significantly after 2 months in all groups, and the decline was proportional to the reduction in body fat, because leptin levels adjusted for body fat did not change after treatment. CSF leptin levels showed a significant decrease after 2 months in all groups, and this decline was higher on group III compared with group I (P = 0.006). After therapy, the CSF/serum leptin ratio did not change in group I (1.57 +/- 0.3 to 1.72 +/- 0.62%) and group II (1.78 +/- 1.01 to 1.69 +/- 1.27%), whereas it declined significantly in group III (1.65 +/- 0.43 to 1.09 +/- 0.47%; P < 0.01), corresponding to a decrease of 33.3 +/- 22.5% for the CSF/serum leptin ratio. The percentage change in group III was significantly different from the positive variation on group I (11.9 +/- 42.1%; P = 0.006) and close to the statistical significance compared with the negative variation seen in group II (-7.6 +/- 27.8%; P = 0.06). Our results showed that the CSF/serum leptin ratio decreased after weight loss in obese women treated during 2 months with orlistat, whereas this ratio did not change in this period of time in obese women treated with fenproporex and sibutramine.     

RESEARCH INTO PAIN PERCEPTION WITH ARTERIOVENOUS FISTULA (AVF) CANNULATION

Patients with end‐stage renal failure (ESRF) undergoing haemodialysis (HD) are repeatedly exposed to stress and pain from approximately 300 punctures per year to their arteriovenous fistula (AVF). Repeated AVF punctures lead to a considerable degree of pain, due to the calibre and length of the bevel of fistula needles. Pain is a sensitive, emotional and subjective experience. The objective of this study was to measure pain associated with AVF needling. The analogue visual scale (AVS) divided into 10 equal parts (0 indicating lack of pain, and 10 unbearable pain) was used. Patients⁷ perceptions were measured in three different HD sessions. Pain was considered mild during AVF needling. The buttonhole technique caused a mean degree of pain of 2.4 (±1.7), compared to 3.1 (±2.3) using the conventional ropeladder technique. Although without reaching a statistically significant difference, diminished pain was associated with the buttonhole technique.     

New insights in the pathogenesis of IgA nephropathy

IgA nephropathy (N) or Berger's disease is the most common form of primary glomerulonephritis worldwide and one of the first cause of end-stage renal failure. The disease is characterized by the accumulation in mesangial areas of complexes containing polymeric IgA1. The mechanisms involved in the pathogenesis of IgAN is only now emerging. We discussed here three essential points: (i) the generation of abnormal IgA1 and formation of IgA1 complexes; (ii) the generation of mesangial injury mediated by interaction of IgA1 complexes with mesangial IgA1 receptors, and (iii) the progression of IgA-mediated mesangial injury towards renal failure. In summary, our data reveal that quantitative and structural changes of IgA1 play a key role on the onset of the disease due to functional abnormalities of two IgA receptors: the Fc alphaRI (CD89) expressed by blood myeloid cells and the transferrin receptor (CD71) on mesangial cells. Abnormal IgA induces release of soluble CD89 soluble leading to the formation of circulating IgA complexes, which in turn may be trapped by CD71 that is overexpressed on mesangial cells in IgAN patients allowing formation of IgA1 deposits. The elucidation of IgA-receptor interactions may open new avenues for drug design and treatment of IgAN.     

Immune and Inflammatory Determinants Underlying Alzheimer’s Disease Pathology

Journal of Neuroimmune Pharmacology - This study examines the link between peripheral immune changes in perpetuation of the Alzheimer’s disease (AD) neuropathology and cognitive deficits. Our...     

Macrophagic Myofasciitis in Childhood: The Role of Scanning Electron Microscopy/Energy-Dispersive Spectroscopy for Diagnosis

Macrophagic myofasciitis (MMF) is an inflammatory myopathy related to aluminum-containing vaccines. Described in 1998, most cases were reported in adults, with only 22 cases being reported in children. Three children aged between 13 months and 3½ years were investigated in our institution for neuromuscular symptoms. They underwent thorough clinical, familial, and laboratory investigations, electroneuromyography, muscle biopsy with transmission electron microscopy, scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS), and, in one case, brain magnetic resonance imaging. They had received regular immunizations. Two patients were hypotonic and one presented with myotonia. Muscle biopsy of all patients presented macrophagic infiltrates with intracytoplasmic aluminum content as revealed by SEM/EDS analysis. Their diverse clinical picture does not support a direct relationship between local morphologic findings and systemic symptoms. The atypical clinical presentation of these children may not result from the superposition of MMF upon a background systemic neuromyopathy, suggesting instead that they are two coincident and independent conditions. Although the finding of macrophage infiltrates in muscle tissue is not new, the identification of aluminum content is recent. The use of tissue sections for aluminum detection and mapping by SEM/EDS is conclusive for, diagnosis; it has not been reported previously in a pathology journal, to the authors' knowledge.     

Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence.     

COVID-19 pandemic impacts physical activity levels and sedentary time but not sleep quality in young badminton athletes

Purpose

Regular physical activity is a good strategy to maintain the health of athletes, and prevent pain and decreased joint flexibility during the pandemic. On the other hand, higher sedentary time during the pandemic period can have deleterious effects. The objective of this study was to compare physical activity levels, sedentary time, and sleep parameters during the pre-COVID period and the COVID-19 pandemic period in young badminton athletes.

Methods

Fifteen young badminton athletes were evaluated during a pre-COVID period (July 2019) and during the COVID-19 period (July 2020). Sleep parameters, physical activity level, and sedentary time were measured using a tri-axial accelerometer. Participants wore the accelerometer on their dominant wrist for 7 days consecutively. In addition, the average of each sleep parameter [time in bed and total sleep time in hours per day, sleep efficiency (%), wake after sleep onset (WASO, total per day), and sleep latency (minutes per day)] was reported over the 7-day period.

Results

Athletes presented increased sedentary time (pre-COVID?=?7.0?±?1.1 vs.COVID-19?=?8.9?±?1.9 h/day, p?=?0.004, d?=?1.30) and significant decreases in the total PA observed in counts per day (pre-COVID?=?2,967,064.4?±?671,544.1 vs. COVID-19?=?1,868,210.2?±?449,768.4 counts/day, p?=?0.001, d?=?1.99), time in vigorous PA (pre-COVID?=?7.7?±?0.9 vs. COVID-19?=?6.1?±?1.2 h/day, p?=?0.001, d?=?1.56), and time in moderate-to-vigorous PA (pre-COVID?=?8.1?±?0.9 vs. COVID-19?=?6.5?±?1.3 h/day, p?=?0.001, d?=?1.48). There were no significant differences for time in light and moderate PA or in sleep parameters (p?>?0.05).

Conclusion

Young badminton athletes presented increased sedentary time, and decreased total physical activity, time in MVPA, and time in vigorous activities during the COVID-19 pandemic compared to the pre-COVID period, however, there were no significant differences in sleep parameters.