Nanomedicine in kidney disease.

PURPOSE OF REVIEW: The pathophysiological understanding of kidney-related disorders has profoundly increased; however, tissue-specific and cell-specific treatments in this field remain scarce. Advances in nanomedicine enable alteration of pharmacokinetics and targeted treatments improving efficiency and reducing toxicity. This review addresses recent developments of nanocarriers used for various purposes in the broad field of kidney disease, which may pave a path to new therapeutic and diagnostic solutions employing nanomedicine. RECENT FINDINGS: Controlled delivery of antiproliferative medications enables improved treatment of polycystic kidney disease and fibrosis. Directed anti-inflammatory treatment mitigated glomerulonephritis and tubulointerstitial nephritis. Multiple injury pathways in AKI have been targeted, with therapeutic solutions for oxidative stress, mitochondrial dysfunction, local inflammation and improving self-repair mechanisms. In addition to such treatment development, noninvasive early detection methods (minutes after ischemic insult) have been demonstrated as well. Sustained release of therapies that reduce ischemia-reperfusion injury as well as new aspects for immunosuppression bring hope to improving kidney transplant outcomes. The latest breakthroughs in gene therapy are made achievable by engineering the targeted delivery of nucleic acids for new treatments of kidney disease. SUMMARY: Recent advances in nanotechnology and pathophysiological understanding of kidney diseases show potential for translatable therapeutic and diagnostic interventions in multiple etiologies of kidney disease.

Return to training in the COVID-19 era: The physiological effects of face masks during exercise.

COVID-19 outbreak has a profound impact on almost every aspect of life. Universal masking is recommended as a means of source control. Routinely exercising in a safe environment is an important strategy for healthy living during this crisis. As sports clubs and public spaces may serve a source of viral transmission, masking may become an integral part of physical activity. This study aimed to assess the physiological effects of wearing surgical masks and N95 respirators during short-term strenuous workout. This was a multiple cross-over trial of healthy volunteers. Using a standard cycle ergometry ramp protocol, each subject performed a maximal exercise test without a mask, with a surgical mask, and with an N95 respirator. Physiological parameters and time to exhaustion were compared. Each subject served his own control. Sixteen male volunteers (mean age and BMI of 34 ± 4 years and 28.72 ± 3.78 kg/m2 , respectively) completed the protocol. Heart rate, respiratory rate, blood pressure, oxygen saturation, and time to exhaustion did not differ significantly. Exercising with N95 mask was associated with a significant increase in end-tidal carbon dioxide (EtCO2 ) levels. The differences were more prominent as the load increased, reaching 8 mm Hg at exhaustion (none vs N95, P = .001). In conclusion, in healthy subjects, short-term moderate-strenuous aerobic physical activity with a mask is feasible, safe, and associated with only minor changes in physiological parameters, particularly a mild increase in EtCO2 . Subjects suffering from lung diseases should have a cautious evaluation before attempting physical activity with any mask.

Are corticosteroids or end-stage renal failure associated with an afebrile presentation of Gram-negative bacteraemia?

OBJECTIVES: Assertions regarding afebrile presentation of sepsis frequently lead to superfluous antibiotic treatment. This study aimed to identify the risk factors for afebrile presentation of bacteraemia, focusing on glucocorticoid (GC) treatment and end-stage renal disease (ESRD). METHODS: This retrospective cohort study included all patients with bacteraemia caused by common Gram-negative bacteria in one hospital. The exposure variables were GC treatment, administered for at least 48 hours before bacteraemia onset, and ESRD, defined as patients undergoing dialysis. Risk factors were assessed for afebrile presentation, defined as temperature between 36.0-37.7°C for all measurements, 48 hours prior to blood culture collection. Analyses were subgrouped by community-onset and hospital-acquired Gram-negative bacteraemia (GNB). Propensity score (PS)-weighted multivariate analyses were conducted. RESULTS: Of 4179 patients with GNB, 1090 (26.1%) presented without fever before blood culture collection. In community-onset GNB, GC treatment was significantly associated with afebrile presentation, PS-weighted OR 1.42 (95% CI 1.25-1.61), absolute risk increase 7% (95% CI 4.3-9.8%), while ESRD was not. For hospital-acquired GNB, ESRD was significantly associated with afebrile presentation (OR 1.53; 95% CI 1.25-1.86; absolute risk increase 8.5%; 95% CI 4.4-13.1%); GC was not. Other risk factors for afebrile presentation in both subgroups included increasing Charlson comorbidity score, bacteraemia with non-fermenters Pseudomonas aeruginosa or Stenotrophomonas maltophilia (compared with Enterobacteriaceae), and lower albumin levels. Aging was not associated with afebrile presentation of GNB. CONCLUSION: Although significant associations between GC and ESRD and afebrile presentation of GNB were observed, they were different in community-onset and hospital-acquired GNBs, and absolute risk increases were small.

Standard pre-travel consultation versus shorter consultation combined with smartphone support: a randomized controlled trial.

Immediate and long-term recalls of a pre-travel consultation are suboptimal. We aimed to assess the role of online consultation for travellers.We randomized travellers into two study groups. In the intervention arm, each traveller was given a short pre-travel consultation of 8-12 minutes, combined with the option of smartphone support before and during the trip. In the control arm, each traveller was given a standard length pre-travel consultation of 18-22 minutes. Endpoints included knowledge about potential risks, travellers' satisfaction, time allocated to each traveller and clinical events.We enrolled 75 patients in the intervention group and 74 patients in the control group. Online consultation was used 33 times, by 24 travellers, both before and during the trip. Important health hazards that were addressed included animal and insect bites (8), treatment of diarrhea (4), malaria prophylaxis (2) and altitude sickness prophylaxis (5). Other consultations consisted mainly of reassurances of worried travellers and provision of data. Knowledge about travel-related risks was higher in the control group before travelling (8.86 ± 1.12 vs 8.34 ± 1.32, P = 0.014), and there was a trend towards higher levels of knowledge also during the trip (8.29 ± 1.35 vs 7.89 ± 1.39, P = 0.06). Travellers' satisfaction before and during the trip was similar in both groups: median 10 (10, 10) in both groups before traveling (P = 0.51) and median 9 (8, 10) in both groups during the trip (P = 0.71). In the intervention group, time allocated to each traveller was <12 minutes. There were no differences in the number of clinical events (P > 0.2 for all comparisons).Online WhatsApp support addressed several important travel-related hazards but, when combined with a shortened pre-travel consultation, was associated with a lower level of knowledge about health risks. Therefore, such smartphone support should augment, rather than replace, pre-travel consultation.

Unexpected bleeding after Exenatide treatment: a causative relationship or a coincidence?

OBJECTIVES: Diabetes mellitus is an endemic disease of the current era. It is important to treat it properly. All antidiabetic medications have side effects and various safety profiles. CASE REPORT: Fifty-two years old patient with type II diabetes mellitus, who had spontaneous cutaneous and intra muscular bleeding after starting treatment with Exenatide. The patient's history did not include any kind of spontaneous bleeding. Investigations did not reveal abnormal platelets count and function or coagulation profile. The use of the Exenatide was discontinued and during one year of follow-up, the patient did not experience an additional occurrence of spontaneous bleeding. CONCLUSIONS: To the best of our knowledge, this is the first report of spontaneous bleeding probably caused by Exenatide. The exact pathophysiology, by which the drug can cause spontaneous bleeding, is still not clear and has to be revealed.

[Compliance and safety of oseltamivir treatment in children and infants less than one year of age].

BACKGROUND: Data regarding the compliance and safety of oseltamivir in infants < 1-year-old are limited. AIM: To compare the rates of adverse effects and compliance with oseltamivir treatment among hospitalized children aged < 1-year-old with suspected influenza and older children. METHODS: A telephone follow-up was carried out with parents of children admitted to hospital during the 2009-influenza pandemic within a week after their discharge, and their medical records were reviewed. RESULTS: A total of 89 children were included (median age was 1.3 years old); 38.2% were < 1-year-old. Only 9% were diagnosed with pH1N1 influenza. The mean duration of therapy was 3 days. Difficulty in the administration of oseltamivir was reported in 52.8% of the children. Adverse effects were reported in 53.9% of the children. The most common were vomiting and/or diarrhea (32.6%) followed by restlessness (31.8%), and rash (6.7%). Treatment of only one child was discontinued due to a possible adverse event. The rates of adverse effects and difficulties in oseltamivir administration were similar among infants < 1-yr-old and older children. CONCLUSIONS: The compliance and safety of oseltamivir therapy were similar among infants < 1-yr-old and older children. Difficulties in oseltamivir administrating and/or possible adverse effects have rarely influenced compliance. Liberal treatment with oseltamivir has led to prominent overuse of the medication.