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Background and Objectives: The preferred osmotic agent used for brain relaxation during craniotomies remains unclear, either mannitol (MAN) or hypertonic saline (HTS). Hence, we sought to compare these solutions in this population., Methods: MEDLINE, Embase, and Cochrane databases were systematically searched until August 02, 2023. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed using I2 statistics. Meta-regression analysis was conducted to evaluate a possible link between Brain Relaxation Score and tumor volume. R, version 4.2.3, was used for statistical analysis., Results: A total of 16 randomized controlled trials and 1031 patients were included, of whom 631 (61%) underwent surgery for supratentorial tumor resection. Compared with MAN, HTS achieved better rates of brain relaxation (80% vs 71%; odds ratio [OR] 1.68; 95% CI 1.22-2.33; P = .001; I2 = 0%), which was also demonstrated in the subgroup analysis of patients with supratentorial brain tumor (78% vs 65%; OR 2.02; 95% CI 1.36-2.99; P = .0005; I2 = 0%); a minor number of patients requiring a second dose of osmotic agent (14% vs 28%; OR 0.43; 95% CI 0.27-0.69; P = .0003; I2 = 0%); a lower fluid intake (mean difference -475.9341 mL; 95% CI -818.8952 to -132.9730; P = .007; I2 = 88%); and lower urine output (mean difference -462.0941 mL; 95% CI -585.3020 to -338.8862; P = <.001; I2 = 96%). Hospital length of stay and focal neurological deficits did not reach a statistically significant difference between groups., Conclusion: In this updated meta-analysis, consistent results suggest that HTS is associated with more beneficial outcomes than MAN in patients undergoing craniotomy., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objectives: Controlling elevated intracranial pressure following brain injury with hyperosmolar agents is one of the mainstay treatments in traumatic brain injury patients. In this study, we compared the effects of hypertonic saline (HS) and mannitol in reducing increased intracranial pressure., Methods: A total of 637 patients from 15 studies were included in our meta-analysis. The primary outcomes were mortality, the length of stay in the hospital and ICU, and the Glasgow Outcome Scale at follow-up., Results: The mortality in the mannitol group was not statistically different compared to the HS group (RR = 1.55; 95% CI = [0.98, 2.47], p  = 0.06). The length of stay in the ICU was significantly shorter in the HS group (MD = 1.18, 95% CI = [0.44, 1.92], p  < 0.01). In terms of favorable neurological outcomes, there was no significant difference between the two agents (RR = 0.92, 95% CI = [0.11, 7.96], p  = 0.94). The duration of the effect was shorter in the mannitol group than in the HS group (MD = -0.67, 95% CI = [-1.00, -0.33], p  < 0.01)., Discussion: The results showed that HS and mannitol had similar effects in reducing ICP. Although the HS was associated with a longer duration of effect and shorter ICU stay, other secondary outcomes including mortality rate and favorable neurological outcomes were similar between the two drugs. In conclusion, considering the condition of each patient individually, HS could be a reasonable option than mannitol to reduce ICP in TBI patients.

Objective: Postoperative delirium (POD), especially after cardiac surgery with cardiopulmonary bypass (CPB), is a relatively common and severe complication increasing side effects, length of hospital stay, mortality and healthcare resource costs. This study aimed to determine the impact of using mannitol serum in the prime of CPB for preventing the occurrence of delirium in patients undergoing coronary artery bypass surgery., Methods: This study is a single-centre, double-blinded, randomised, controlled trial that was conducted from December 2022 to May 2023. Patients in the age range of 18-70 who underwent elective coronary artery bypass surgery were included in the study. In the control group (n=45), the prime solution included Ringer's lactate serum. In the intervention group (n=45), the prime solution consisted of 200 mL mannitol serum and Ringer's lactate serum. The primary outcome of the study was the incidence of POD. Secondary outcomes included the duration of mechanical ventilation, length of stay in the intensive care unit (ICU) and 30-day in-hospital mortality., Results: There were no statistically significant differences in demographic characteristics and risk factors between the control and intervention groups (p<0.05). However, the incidence of POD was significantly lower in the intervention group compared with the control group (22.25% vs 42.2%, p=0.035). There were no significant differences between the two groups regarding CPB time, aortic cross-clamp time, duration of mechanical ventilation and length of stay in ICU (p<0.05). Additionally, mortality rates and rates of return to the operating room did not differ significantly between the two groups (p<0.05)., Conclusions: This study concluded that adding mannitol to the prime of CPB pump can help reduce the incidence of delirium after cardiac surgery., Trial Registration Number: IRCT20221129056660N1., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Importance: Occurrence of mydriasis during the prehospital management of traumatic brain injury (TBI) may suggest severe intracranial hypertension (ICH) subsequent to brain herniation. The initiation of hyperosmolar therapy to reduce ICH and brain herniation is recommended. Whether mannitol or hypertonic saline solution (HSS) should be preferred is unknown., Objectives: The objective of this study is to assess whether HSS, compared with mannitol, is associated with improved survival in adult trauma patients with TBI and mydriasis., Design/setting and Participants: A retrospective observational cohort study using the French Traumabase national registry to compare the ICU mortality of patients receiving either HSS or mannitol. Patients aged 16 years or older with moderate to severe TBI who presented with mydriasis during prehospital management were included., Outcome Measures and Analysis: We performed propensity score matching on a priori selected variables [i.e. age, sex and initial Coma Glasgow Scale (GCS)] with a ratio of 1 : 3 to ensure comparability between the two groups. The primary outcome was ICU mortality. The secondary outcomes were regression of pupillary abnormality during prehospital management, pulsatility index and diastolic velocity on transcranial Doppler within 24 h after TBI, early ICU mortality (within 48 h), ICU and hospital length of stay., Results: Of 31 579 patients recorded in the registry between 2011 and 2021, 1417 presented with prehospital mydriasis and were included: 1172 (82.7%) received mannitol and 245 (17.3%) received HSS. After propensity score matching, 720 in the mannitol group matched 240 patients in the HSS group. Median age was 41 years [interquartile ranges (IQR) 26-60], 1058 were men (73%) and median GCS was 4 (IQR 3-6). No significant difference was observed in terms of characteristics and prehospital management between the two groups. ICU mortality was lower in the HSS group (45%) than in the mannitol group (54%) after matching [odds ratio (OR) 0.68 (0.5-0.9), P  = 0.014]. No differences were identified between the groups in terms of secondary outcomes., Conclusion: In this propensity-matched observational study, the prehospital osmotherapy with HSS in TBI patients with prehospital mydriasis was associated with a lower ICU mortality compared to osmotherapy with mannitol., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mannitol is used in the treatment of raised intracranial pressure (ICP). The aim of this study was to investigate whether mannitol (MAN) leads to a relevant deterioration in platelet function in routine neurosurgical procedures., Methods: Thirty-eight patients undergoing elective craniotomy due to a brain tumor with elevated ICP were included. After induction of anesthesia a blood sample was taken (T1). The patients then received 1 g∙kg -1 MAN within 30 minutes. The second blood sample (T2) was obtained 60 minutes after T1. Blood samples were examined by means of aggregometry (Multiplate ® ; Roche, Basel, Switzertland) and PFA-100 ® tests (Siemens Healthineers, Erlangen, Germany)., Results: No patient had clinical signs of increased bleeding. We could not find any deterioration in the aggregometry using Multiplate ® (Roche), neither in the adenosine diphosphate (ADP), the arachidonic acid (ASPI), or the thrombin receptor activating protein (TRAP) test. PFA-100 ® (Siemens Healthineers) closing times (cT) showed a significant prolongation between T1 and T2: collagen/adenosine diphosphate (COL/ADP) test 79 s [70/99] and 91 s [81/109]; P=0.002); collagen/epinephrine (COL/EPI) test 109 s [92/129] and 122 s [94/159]; P=0.0004). A subgroup analysis showed that the patients who received isotonic balanced infusions only, had no prolongation of cT, whereas the patients who received additionally gelatin solution had a significant prolongation. COL/ADP: 78 s [70/98] and 91 s [82/133]; P=0.0004). COL/EPI: test 111 s [92/128] and 127 s [103/146]; P=0.0026). Except for individual outliers, the measured values were in the normal range., Conclusions: In this study, we found no clinically relevant deterioration of platelet function in neurosurgical patients with increased ICP after administration of MAN. Changes that occurred were all within normal ranges.

Objective: Osmotherapeutic agents increase the intravascular volume by withdrawing water from the brain followed by relative hypovolemia due to diuresis leading to significant changes in systemic hemodynamics which might have adverse consequences in the elderly. We studied the effect of mannitol (20%) and hypertonic saline (HTS) (3%) on left ventricular outflow tract velocity time integral (LVOT-VTI) and cardiac output (CO) in elderly patients undergoing supratentorial neurosurgical procedures using transesophageal echocardiography., Methods: We recruited 28 patients aged above 65 years undergoing supratentorial craniotomy who received equiosmolar solutions of 5.35 ml/kg of 3% HTS (group HS, n = 14) or 5 ml/kg of 20% mannitol (group M, n = 14). LVOT-VTI was recorded at baseline, 15, 30, 45, 60, and 90 minutes postinfusion and CO was derived. We also recorded heart rate, blood pressure, fluid balance, brain relaxation, vasopressor use, complications, and neurological outcome., Results: We found a significant decrease in LVOT-VTI at 45, and 60 minutes in group M as compared to group HS [mean (standard deviation), 16.76 (1.81) vs. 20.78 (1.87), P < 0.001, 17.4 (2.38) vs. 19.16 (2), P = 0.044, respectively]. We also found a corresponding significant fall in CO [3863.16 (845.87) vs. 4745.59 (1209.33) ml/minute, P = 0.034] and systolic blood pressure (P = 0.039), at 45 minutes in group M. Urine output was higher in group M (P < 0.001). All other parameters were comparable., Conclusions: HTS appears to be associated with better systemic hemodynamics (LVOT-VTI, CO) while providing equivalent brain relaxation as mannitol in elderly patients. A future larger study is required to confirm our preliminary findings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives : The relationship between histidine-tryptophan-ketoglutarate (HTK)-induced hyponatremia and brain injury in adult cardiac surgery patients is unclear. This study analyzed postoperative neurological outcomes after intraoperative HTK cardioplegia infusion. Materials and Methods : A prospective cohort study was conducted on 60 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Of these patients, 13 and 47 received HTK infusion and conventional hyperkalemic cardioplegia, respectively. The patients' baseline characteristics, intraoperative data, brain injury markers, Mini-Mental State Examination (MMSE) scores, and quantitative electroencephalography (qEEG) data were collected. Electrolyte changes during cardiopulmonary bypass, the degree of hyponatremia, and any associated brain insults were evaluated. Results : The HTK group presented with acute hyponatremia during cardiopulmonary bypass, which was intraoperatively corrected through ultrafiltration and normal saline administration. Postoperative sodium levels were higher in the HTK group than in the conventional cardioplegia group. The change in neuron-specific enolase levels after cardiopulmonary bypass was significantly higher in the HTK group ( p = 0.043). The changes showed no significant differences using case-control matching. qEEG analysis revealed a significant increase in relative delta power in the HTK group on postoperative day (POD) 7 ( p = 0.018); however, no significant changes were noted on POD 60. The MMSE scores were not significantly different between the two groups on POD 7 and POD 60. Conclusions : HTK-induced acute hyponatremia and rapid correction with normal saline during adult cardiac surgeries were associated with a potential short-term but not long-term neurological impact. Further studies are required to determine the necessity of correction for HTK-induced hyponatremia.

Secondary brain injury after intracerebral hemorrhage (ICH) is the main cause of poor prognosis in ICH patients, but the underlying mechanisms remain less known. The involvement of Piezo1 in brain injury after ICH was studied in a mouse model of ICH. ICH was established by injecting autologous arterial blood into the basal ganglia in mice. After vehicle, Piezo1 blocker, GsMTx4, Piezo1 activator, Yoda-1, or together with mannitol (tail vein injection) was injected into the left lateral ventricle of mouse brain, Piezo1 level and the roles of Piezo1 in neuronal injury, brain edema, and neurological dysfunctions after ICH were determined by the various indicated methods. Piezo1 protein level in neurons was significantly upregulated 24 h after ICH in vivo (human and mice). Piezo1 protein level was also dramatically upregulated in HT22 cells (a murine neuron cell line) cultured in vitro 24 h after hemin treatment as an in vitro ICH model. GsMTx4 treatment or together with mannitol significantly downregulated Piezo1 and AQP4 levels, markedly increased Bcl2 level, maintained more neurons alive, considerably restored brain blood flow, remarkably relieved brain edema, substantially decreased serum IL-6 level, and almost fully reversed the neurological dysfunctions at ICH 24 h group mice. In contrast, Yoda-1 treatment achieved the opposite effects. In conclusion, Piezo1 plays a crucial role in the pathogenesis of brain injury after ICH and may be a target for clinical treatment of ICH., Competing Interests: Declaration of competing interest The author declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acute lung injury (ALI) remains a significant global health issue, necessitating novel therapeutic interventions. In our latest study, we pioneered the use of D-mannitol-cerium-quercetin/rutin coordination polymer nanoparticles (MCQ/R NPs) as a potential treatment for ALI. The MCQ/R NPs, which integrate rutin and quercetin for their therapeutic potential and D-mannitol for its pulmonary targeting, displayed exceptional efficacy. By utilizing cerium ions for optimal nanoparticle assembly, the MCQ/R NPs demonstrated an average size of less than 160 nm. Impressively, these nanoparticles outperformed conventional treatments in both antioxidative capabilities and biocompatibility. Moreover, our in vivo studies on LPS-induced ALI mice showed a significant reduction in lung tissue inflammation. This groundbreaking research presents MCQ/R NPs as a promising new approach in ALI therapeutics.

Central neurogenic hyperventilation (CNH) is a rare disease, caused by chemical or mechanical disturbance of respiratory centers. It is characterized by the absence of extracerebral respiratory stimuli. A woman developed severe respiratory alkalosis and lactatemia after resection of a posterior fossa meningioma despite lack of cardio-respiratory or metabolic alterations. Cerebral computed tomography (cCT) revealed edema of the pontomedullary area. Treatment with mannitol and dexamethasone reestablished normal breathing patterns. Lactatemia was likely due to reduced splanchnic lactate utilization. Intracranial pathologies should be suspected in case of hyperventilation without overt reasons. cCT to confirm edema or ischemia and prompt treatment is suggested., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m 2 , and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m 2 ) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients., (© 2024. The Author(s).)

Background: The removal of the lower third molar is a routine procedure in oral surgery, yet it often leads to postoperative side effects, particularly inflammation. Despite various interventions explored in prior studies, there is still a need for effective strategies, such as anti-inflammatory substances, to address postoperative side effects., Purpose: The purpose of this study is to answer the following clinical question: Does the local injection of 0.9 M mannitol reduce postoperative pain, trismus, and swelling in patients undergoing bilateral symmetrically impacted mandibular third molar extraction?, Study Design, Setting, Sample: This prospective, single-blind, split-mouth study at Hamadan Dental School involved 30 patients with bilateral symmetrically impacted mandibular third molars. Inclusion criteria were: no current medication, no anesthesia allergies, bilateral symmetrically impacted mandibular third molars, non-smokers, and the absence of systemic diseases. Exclusion criteria were: poor oral hygiene, alcohol/cigarette use, drug consumption, diabetes, systemic/gastrointestinal disorders, infection at the surgical site, lack of patient cooperation, and mannitol/anesthetic allergy., Predictor/exposure/independent Variable: The predictor variable was therapeutic injection, and it was grouped into two categories, 0.9 M mannitol solution or distilled water., Main Outcome Variable: The primary outcome variable was pain. Secondary outcomes are trismus, swelling, patient satisfaction, and analgesic consumption., Covariates: Covariates included demographic information and operative details., Analyses: Statistical analyses included repeated measures and paired t-tests with a significance level set at P < .05., Results: The study comprised 30 participants (mean age: 22.6 ± 3.59 years; 6 men, 24 women). In the test group, pain intensity significantly decreased from 5.30 on surgery day to 0.00, with subsequent values of 2.97, 1.30, 0.40, 0.17, and 0.03. The control group also decreased from 7.68 to 0.00, with values of 4.73, 2.67, 0.97, 0.23, and 0.07. The difference was statistically significant (P < .001). No significant swelling differences at T1, T3, T5, and T7 (P > .05). The intervention group had improved maximum mouth opening at T1, T3, T5, and T7 (P = .011) compared to the control group., Conclusion and Relevance: Mannitol infiltration significantly reduces postoperative pain and trismus in impacted third molar surgery. This finding underscores the potential for improved patient comfort and recovery in this context., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: In the last decade, del Nido cardioplegia has been embedded in adult cardiac surgery involving CABG and aortic valve surgical procedures. We reviewed our early experience with del Nido cardioplegia in the setting of minimally invasive mitral valve surgery., Methods: Data on 120 consecutive patients operated between 03/2021 and 06/2022 were retrieved from our internal database (infective endocarditis and urgent operations were excluded). Patients were divided into two groups according to the use of Histidine-Tryptophan-Ketoglutarate or del Nido cardioplegia. A propensity match analysis was performed using thirteen preoperative and intraoperative variables. Several intraoperative data and early postoperative outcomes were investigated, including cardiac enzymes (Troponin I HS and CK-MB) measured upon arrival in the Intensive Care Unit (ICU), after 12 hours and everyday thereafter., Results: There was no difference in preoperative characteristics and surgical techniques between both unmatched and matched Histidine-Tryptophan-Ketoglutarate and del Nido populations. Patients in the del Nido group received a lower volume of cardioplegia ( p < 0.001) and ultrafiltration during CPB ( p < 0.001). Histidine-Tryptophan-Ketoglutarate was associated with a lower rate of post cross-clamp spontaneous defibrillation ( p < 0.001) and showed a lower level of blood sodium after CPB ( p < 0.001). The release of cardiac enzymes was similar between the two groups ( p = 0.72). There was no difference in terms of postoperative morbidity and 30 day mortality., Conclusions: del Nido cardioplegia in the setting of minimally invasive mitral valve surgery seemed safe with acceptable myocardial protection and excellent early outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. FundingThe author(s) received no financial support for the research, authorship, and/or publication of this article.

Airway hyper-responsiveness (AHR) is a tenet of the persistent asthma phenotype along with reversible airway obstruction and type 2 (T2) inflammation. Indirect acting challenges such as mannitol are more closely related to the underlying T2 inflammatory process as compared with direct challenges. In this review article, we summarise the current literature and explore the future role of mannitol AHR in clinical remission with biologics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: In this study, we evaluated if modified Del Nido cardioplegia delivers comparable cardiac protection in comparison to Custodiol® in patients undergoing isolated minimally invasive mitral valve repair., Methods: From January 2018 to October 2021, all patients undergoing non-emergent isolated minimally invasive mitral valve repair were included in this study. The cardioplegia was chosen at the surgeons' discretion. The primary end points of this study were peak postoperative cardiac enzyme levels. Secondary end points were in-hospital mortality, hospital stay, occurrence of cardiac arrhythmias, pacemaker implantations, postoperative lactate and sodium levels and postoperative incidence of renal failure requiring dialysis., Results: A total of 355 patients were included in this study. The mean age of patients was 57. After propensity score matching, a total of 156 pairs were identified. There was no difference in cross-clamp time between both groups. Postoperative creatine kinase levels were higher in patients receiving Custodiol on the 1st and 2nd postoperative days. Creatine kinase isoenzyme MB levels were higher in patients receiving Custodiol on the 2nd postoperative day (0.5 ± 0.2 vs 0.4 ± 0.1 µmol/l s; P < 0.001). Postoperative Troponin T concentrations were similar between both groups. Maximum lactate concentrations were higher in patients receiving Custodiol on the day of surgery (2.4 ± 1.9 vs 2.0 ± 1.1 mmol/l; P = 0.04). The overall hospital stay was longer in patients receiving Del Nido cardioplegia (10.6 ± 3.2 vs 8 ± 4.1 days; P < 0.01)., Conclusions: Modified Del Nido cardioplegia based on Ionosteril® solution offers equivalent protection compared to Custodiol for isolated minimally invasive mitral valve repair., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Purpose of Review: To review relevant advances in the past half-decade in the treatment of primary brain tumors via modification of blood-brain barrier (BBB) permeability., Recent Findings: BBB disruption is becoming increasingly common in the treatment of primary brain tumors. Use of mannitol in BBB disruption for targeted delivery of chemotherapeutics via superselective intra-arterial cerebral infusion (SIACI) is the most utilized strategy to modify the BBB. Mannitol is used in conjunction with chemotherapeutics, oligonucleotides, and other active agents. Convection-enhanced delivery has become an attractive option for therapeutic delivery while bypassing the BBB. Other technologic innovations include laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) which have emerged as prime modalities to directly target tumors and cause significant local BBB disruption. In the past 5 years, interest has significantly increased in studying modalities to disrupt the BBB in primary brain tumors to enhance treatment responses and improve clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: A topic of current research is the development of a new approach to the diagnosis and treatment of severe brain injury taking into consideration its main pathophysiological mechanism-idiopathic intracranial hypertension syndrome. The goal of this study was to identify Doppler patterns of unfavorable craniocerebral injury conditions to form a consistent algorithm of treatment measures to reduce secondary brain damage in patients with severe craniocerebral trauma., Methods: Transcranial Doppler imaging is a prospective method, which allows quick and noninvasive assessment of the intracerebral blood flow dynamics right at the patient's bedside. Due to the operator-dependent nature of this method, clinical interpretation can often be contradictory. As a result, no clear criteria for therapy correction have yet been formulated based on this neuroimaging method., Results: Analysis of the therapy performed allowed us to specify the options for the hyperosmolar solutions for the correction of idiopathic intracranial hypertension syndrome., Conclusions: No statistically significant difference in effectiveness was shown between mannitol and hypertonic saline solutions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose of the Study: A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 20% mannitol and 3% hypertonic saline (HS) during elective supratentorial brain tumour surgery in patients with midline shift., Material and Methods: Sixty patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 5mL/kg of 20% mannitol (n=30) or 3% HS (n=30) administered at skin incision. P CO2 in arterial blood was maintained within 35-40mmHg and arterial blood pressure was controlled within baseline values ±20%. The primary outcome was the proportion of satisfactory brain relaxation. The surgeon assessed brain relaxation on a four-point scale (1=excellent with no swelling, 2=minimal swelling, 3=serious swelling not requiring treatment, 4=severe swelling requiring treatment). Postsurgical intracranial changes determined by imaging techniques, postoperative complications, PACU and hospital stay, and mortality at 30 days were also recorded. Appropriate statistical tests were used for comparison; P<0.05 was considered as significant. This trial was registered in Eudract.ema.europa.eu (#2021-006290-40)., Results: There was no difference in brain relaxation: 2.00 [1.00-2.00] and 2.00 [1.75-3.00] for patients in mannitol and HS groups, respectively (P=0.804). Tumour size (OR: 0.99, 95% CI: 0.99-1.01; P=0.371), peritumoral oedema classification (OR: 0.57, 95% CI: 0.11-2.84; P=0.493), mass effect (OR: 0.86, 95% CI: 0.16-4.87; P=0.864), anaesthesia (OR: 4.88, 95% CI: 0.82-28.96; P=0.081) and midline shift (OR: 5.00, 95% CI: 0.84-29.70; P=0.077) did not have a significant influence on brain swelling in patients treated with either mannitol or HS. No significant differences in perioperative outcomes, mortality and length of PACU and hospital stay were observed., Conclusions: 5mL/kg of 20% mannitol or 3% HS result in similar brain relaxation scores in patients undergoing craniotomy for supratentorial brain tumour with midline shift., (Copyright © 2022 Sociedad Española de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To analyze the application effect of continuous lumbar cistern fluid drainage combined with decompressive craniectomy in the treatment of severe craniocerebral injury., Methods: A total of 87 patients with severe craniocerebral injury admitted to our hospital between March 2016 and March 2021 were retrospectively enrolled. They were divided into two groups according to the decompression methods applied, with 42 patients who received standard decompressive craniectomy assigned to the control group and 45 patients who received continuous lumbar cistern fluid drainage combined with standard decompressive craniectomy assigned to the observation group. The primary indicators that were monitored and compared between the two group included the amount of time for patient CT imaging to be clear of subarachnoid hemorrhage, the length-of-stay, the duration of post-operative intubation, the mannitol dose, scores for Glasgow Coma Scale (GCS), prognosis, the incidence of cerebral edema and cerebral infarction, and complications. The secondary indicators that were monitored and compared included intracranial pressure, cerebrospinal fluid antinucleosome protein SP100, and red blood cell count of the two groups before treatment and after continuous drainage for 7 days., Results: The amount of time for CT imaging to be clear of subarachnoid hemorrhage and the length-of-stay of the observation group were shorter than those of the control group, the mannitol dose of the observation group was lower than that of the control group, the incidence of cerebral edema and the incidence of complications of the observation group were lower than those of the control group, and the rate of patients with good prognosis in the observation group was higher than that in the control group ( P <0.05). There was no significant difference in the rate of poor prognosis or mortality between the two groups ( P >0.05). The duration of postoperative intubation of the observation group was (8.24±1.09) d, while that of the control group was (9.22±1.26) d, and the difference between the two groups was statistically significant ( t =3.887, P <0.05). There were 2 cases (4.44%) of cerebral infarction in the observation group, with the infarct volume being (8.36±1.87) cm 3 , while there were 9 cases (21.43%) of cerebral infarction in the control group, with the infarct volume being (8.36±1.87) cm 3 , and there were statistically significant differences in the incidence and volume of cerebral infarction between the two groups ( χ 2 =5.674, t =9.609, P <0.05). After treatment, the intracranial pressure and red blood cell count decreased in both groups and the intracranial pressure, cerebrospinal fluid SP100, and red blood cell count of the observation group were significantly lower than those of the control group ( P <0.05). The cerebrospinal fluid SP100 of the observation group decreased after treatment in comparison with the level before treatment ( P <0.05), while the pre- and post-treatment levels of the control group did not demonstrate any significant difference., Conclusion: Continuous lumbar cistern fluid drainage in patients with severe craniocerebral injury effectively shortens the time required for the body to recover, significantly reduces the level of intracranial pressure, improves the levels of cerebral edema and cerebral infarction, and has a high degree of safety for prognosis and recovery., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To compare the efficacy and safety of two hyperosmolar agents (hypertonic saline vs. mannitol) used for the reduction of elevated intracranial pressure (ICP) in children., Methods: A meta-analysis of randomized controlled trials (RCTs) was conducted and GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) of evidence was applied. Relevant databases were searched till 31 st May 2022. Primary outcome was mortality rate., Results: Of 720 citations retrieved, 4 RCTs were included in the meta-analysis (n = 365, male = 61%). Traumatic and non-traumatic cases of elevated ICP were included. There was no significant difference in the mortality rate between the two groups [relative risk (RR), 1.09; (95% confidence interval (CI), 0.74 to 1.6)]. No significant difference was found for any of the secondary outcomes, except serum osmolality (being significantly higher in mannitol group). Adverse events like shock and dehydration were significantly higher in the mannitol group, and hypernatremia in the hypertonic saline group. The evidence generated for primary outcome was of "low certainty", and for secondary outcomes, it varied from "very-low to moderate certainty"., Conclusions: There is no significant difference between hypertonic saline and mannitol used for the reduction of elevated ICP in children. The evidence generated for primary outcome (mortality rate) was of "low certainty", and for secondary outcomes, it varied from "very-low to moderate certainty". More data from high-quality RCTs are needed to guide any recommendation., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objective: Nephrotoxicity is frequent in cisplatin-based chemoradiation of head and neck squamous cell carcinoma (HNSCC). Toxicity outcomes and achieved cisplatin-doses after change of departmental hydration policy are presented., Methods: We performed a retrospective time-series analysis of HNSCC patients undergoing chemoradiation with conventional hydration (CH) between 01/2017 and 09/2018 versus shorter hydration with mannitol (SHM) between 09/2018 and 08/2019 to compare the rate of acute kidney injury (AKI) and cumulative cisplatin dose., Results: Among 113 HNSCC patients, SHM (n = 35) in comparison to CH (n = 78) correlated with less AKI (54.3% vs. 74.4%; p = 0.034) and higher cisplatin doses (82.9% vs. 61.5% ≥200 mg/m 2 ; p = 0.025). AKI ≥grade 2 was lower with SHM (2.9% vs. CH: 22.8%; p = 0.01). AKI occurred more frequently in females (92.6% vs. males: 60.5%, p = 0.002). Females received lower cumulative cisplatin doses (51.9% vs. males: 73.3%; p = 0.037)., Conclusions: We observed less AKI and higher cumulative chemotherapy doses with SHM. Female patients were at higher risk of AKI., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Increased intracranial pressure (ICP) is one of the most important modifiable and immediate threats to critically ill patients suffering from traumatic brain injury (TBI). Two hyperosmolar agents (HOAs), mannitol and hypertonic saline (HTS), are routinely used in clinical practice to treat increased ICP. We aimed to assess whether a preference for mannitol, HTS, or their combined use translated into differences in outcome. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study is a prospective multi-center cohort study. For this study, patients with TBI, admitted to the intensive care unit (ICU), treated with mannitol and/or HTS, and aged ≥16 years were included. Patients and centers were differentiated based on treatment preference with mannitol and/or HTS based on structured, data-driven criteria such as first administered HOA in the ICU. We assessed influence of center and patient characteristics in the choice of agent using adjusted multi-variate models. Further, we assessed the influence of HOA preference on outcome using adjusted ordinal and logistic regression models, and instrumental variable analyses. In total, 2056 patients were assessed. Of these, 502 (24%) patients received mannitol and/or HTS in the ICU. The first received HOA was HTS for 287 (57%) patients, mannitol for 149 (30%) patients, or both mannitol and HTS on the same day for 66 (13%) patients. Two unreactive pupils were more common in patients receiving both (13, 21%), compared with patients receiving HTS (40, 14%) or mannitol (22, 16%). Center, rather than patient characteristics, was independently associated with the preferred choice of HOA ( p -value <0.05). ICU mortality and 6-month outcome were similar between patients preferably treated with mannitol compared with HTS (odds ratio [OR] = 1.0, confidence interval [CI] = 0.4-2.2; OR = 0.9, CI = 0.5-1.6, respectively). Patients who received both also had a similar ICU mortality and 6-month outcome compared with patients receiving HTS (OR = 1.8, CI = 0.7-5.0; OR = 0.6, CI = 0.3-1.7, respectively). We found between-center variability regarding HOA preference. Moreover, we found that center is a more important driver of the choice of HOA than patient characteristics. However, our study indicates that this variability is an acceptable practice given absence of differences in outcomes associated with a specific HOA.

Acutely elevated intracranial pressure (ICP) may have devastating effects on patient mortality and neurologic outcomes, yet its initial detection remains difficult because of the variety of manifestations that it can cause disease states it is associated with. Several treatment guidelines exist for specific disease processes such as trauma or ischemic stroke, but their recommendations may not apply to other causes. In the acute setting, management decisions must often be made before the underlying cause is known. In this review, we present an organized, evidence-based approach to the recognition and management of patients with suspected or confirmed elevated ICP in the first minutes to hours of resuscitation. We explore the utility of invasive and noninvasive methods of diagnosis, including history, physical examination, imaging, and ICP monitors. We synthesize various guidelines and expert recommendations and identify core management principles including noninvasive maneuvers, neuroprotective intubation and ventilation strategies, and pharmacologic therapies such as ketamine, lidocaine, corticosteroids, and the hyperosmolar agents mannitol and hypertonic saline. Although an in-depth discussion of the definitive management of each etiology is beyond the scope of this review, our goal is to provide an empirical approach to these time-sensitive, critical presentations in their initial stages.

Background: Hypertonic saline enhances mucociliary clearance and may lessen the destructive inflammatory process in the airways. This is an update of a previously published review., Objectives: To investigate efficacy and tolerability of nebulised hypertonic saline treatment in people with cystic fibrosis (CF) compared to placebo or other treatments that enhance mucociliary clearance., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also searched ongoing trials databases. Most recent search: 25 April 2022., Selection Criteria: We included randomised and quasi-randomised controlled trials assessing hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with CF (any age or disease severity)., Data Collection and Analysis: Two authors independently reviewed all identified trials and data, and assessed trial quality. We assessed the certainty of the evidence using GRADE. For cross-over trials we stipulated a one-week washout period. We planned to use results from a paired analysis in the review, but this was only possible in one trial. For other cross-over trials, we chose to treat the trials as if they were parallel., Main Results: We included 24 trials (1318 participants, aged one month to 56 years); we excluded 29 trials, two trials are ongoing and six are awaiting classification. We judged 15 of the 24 included trials to have a high risk of bias due to participants' ability to discern the taste of the solutions. Hypertonic saline 3% to 7% versus placebo (stable disease) We are uncertain whether the regular use of nebulised hypertonic saline in stable lung disease leads to an improvement in forced expiratory volume in one second (FEV 1 ) % predicted at four weeks, (mean difference (MD) 3.30%, 95% confidence interval (CI) 0.71 to 5.89; 4 trials, 246 participants; very low-certainty evidence). In preschool children we found no difference in lung clearance index (LCI) at four weeks, but a small improvement after 48 weeks of treatment with hypertonic saline compared to isotonic saline (MD -0.60, 95% CI -1.00 to -0.19; 2 trials, 192 participants). We are also uncertain whether hypertonic saline made a difference to mucociliary clearance, pulmonary exacerbations or adverse events compared to placebo. Hypertonic saline versus control (acute exacerbation) Two trials compared hypertonic saline to control, but only one provided data. There may be little or no difference in lung function measured by FEV 1 % predicted after hypertonic saline compared to isotonic saline (MD 5.10%, 95% CI -14.67 to 24.87; 1 trial, 130 participants). Neither trial reported any deaths or measures of sputum clearance. There were no serious adverse events. Hypertonic saline versus rhDNase Three trials compared a similar dose of hypertonic saline to recombinant deoxyribonuclease (rhDNase); two trials (61 participants) provided data for inclusion in the review. We are uncertain whether there was an effect of hypertonic saline on FEV 1 % predicted after three weeks (MD 1.60%, 95% CI -7.96 to 11.16; 1 trial, 14 participants; very low-certainty evidence). At three months, rhDNase may lead to a greater increase in FEV 1 % predicted than hypertonic saline (5 mL twice daily) at 12 weeks in participants with moderate to severe lung disease (MD 8.00%, 95% CI 2.00 to 14.00; low-certainty evidence). We are uncertain whether adverse events differed between the two treatments. No deaths were reported. Hypertonic saline versus amiloride One trial (12 participants) compared hypertonic saline to amiloride but did not report on most of our outcomes. The trial found that there was no difference between treatments in measures of sputum clearance (very low-certainty evidence). Hypertonic saline compared with sodium-2-mercaptoethane sulphonate (Mistabron®) One trial (29 participants) compared hypertonic saline to sodium-2-mercaptoethane sulphonate. The trial did not measure our primary outcomes. There was no difference between treatments in any measures of sputum clearance, courses of antibiotics or adverse events (very low-certainty evidence). Hypertonic saline versus mannitol One trial (12 participants) compared hypertonic saline to mannitol, but did not report lung function at relevant time points for this review; there were no differences in sputum clearance, but mannitol was reported to be more 'irritating' (very low-certainty evidence). Hypertonic saline versus xylitol Two trials compared hypertonic saline to xylitol, but we are uncertain whether there is any difference in FEV 1 % predicted or median time to exacerbation between groups (very low-certainty evidence). No other outcomes were reported in the review. Hypertonic saline 7% versus hypertonic saline 3% We are uncertain whether there was an improvement in FEV 1 % predicted after treatment with 7% hypertonic saline compared with 3% (very low-certainty evidence)., Authors' Conclusions: We are very uncertain if regular use of nebulised hypertonic saline by adults and children over the age of 12 years with CF results in an improvement in lung function after four weeks (three trials; very low-certainty evidence); there was no difference seen at 48 weeks (one trial; low-certainty evidence). Hypertonic saline improved LCI modestly in children under the age of six years. Evidence from one small cross-over trial in children indicates that rhDNase may lead to better lung function than hypertonic saline at three months; qualifying this, we highlight that while the study did demonstrate that the improvement in FEV 1 was greater with daily rhDNase, there were no differences seen in any of the secondary outcomes. Hypertonic saline does appear to be an effective adjunct to physiotherapy during acute exacerbations of lung disease in adults. However, for the outcomes assessed, the certainty of the evidence ranged from very low to low at best, according to the GRADE criteria. The role of hypertonic saline in conjunction with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy now needs to be considered, and future research needs to focus on this aspect., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Despite extensive study and use, selecting an osmotherapy agent for traumatic brain injury remains a dilemma. This article explores the challenges in managing patients with traumatic brain injury and the ongoing debate surrounding the efficacy of different hyperosmolar agents as treatment options.

Cystic fibrosis (CF) is one of the most common autosomal recessive genetic diseases in Caucasians, but CF patients in China are rare, and it was listed as the first batch of rare diseases in China in 2018. In recent years, CF has been gradually recognized in China, and the number of CF patients reported in China in the past 10 years is more than 2.5 times the total number in the previous 30 years, and the total number of CF patients is estimated to be more than 20 000. The research progress of CF gene modification has led to the innovation of CF treatment. However, the sweat test as an important test for the diagnosis of CF has not been widely implemented in China. At present, the diagnosis and treatment of CF in China still lacks standardized recommendations. In view of these updates, the Chinese Experts Cystic Fibrosis Consensus Committee has formed "the Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis" based on extensive opinion gathering, literatures review, multiple meetings and discussions. This consensus collects 38 core issues related to CF, including pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and patient management. Finally, 32 recommendations were formulated. The consensus used the modified GRADE methodology to grade the evidence evaluation and recommendations. This is the current state of CF consensus in China, and we hope to improve the diagnosis and treatment of CF in China in the future. Summary of recommendations Question 1: How can CF be identified? CF should be suspected if there is: (1) a family history of CF; (2) delayed meconium expulsion or meconium ileus; (3) pancreatic exocrine insufficiency, mainly characterized by long-standing steatorrhea and malnutrition; (4) recurrent lower respiratory tract infections of infantile onset, especially Pseudomonas aeruginosa (PA), Staphylococcus aureus infections of respiratory aetiology; (5) chronic sinusitis, especially when combined with juvenile presentation of nasal polyps; (6) chest CT abnormalities such as the presence of air trapping, bronchiectasis (upper lobe predominant); (7) pseudo-Bartter syndrome; (8) absence of vas deferens in males; (9) clubbing in young bronchiectasis patients(1C). Question 2: What are the diagnostic criteria for CF? 1.1 Presence of one or more of the characteristic clinical manifestations or family history consistent with CF, and meeting at least one of the following definite diagnostic criteria in 1.2 or 1.3.1.2 Sweat chloride testing:(1) Concentrations of more than 60 mmol/L are diagnostic; (2) concentrations between 30-59 mmol/L are intermediate, and genetic variation must be considered to confirm the diagnosis; (3) concentrations less than 30 mmol/L are considered normal.1.3 Genetic testing:(1) Detection of two disease-causing CFTR (cystic fibrosis transmembrane conductance regulator) mutations on biallelic alleles; (2) The CFTR variants are of undetermined significance, but tests such as sweat chloride concentration, intestinal current measurement, or nasal mucosal potential difference suggest abnormal CFTR function, then CF is diagnostic(1C). Question 3: What is the diagnostic process for CF arranged? Sweat chloride testing and CFTR gene analysis are recommended in all patients suspected of CF(1D). Question 4: What is the value of sweat chloride testing in the diagnosis of CF? Sweat chloride testing is the gold standard for the clinical diagnosis of CF(1C). Question 5: What is the value of CFTR genetic testing in Chinese CF diagnosis? Biallelic pathogenic variants of CFTR are a definitive diagnosis of CF(1D). Question 6: What is the diagnostic value of imaging for CF? Chest CT is a sensitive test for early stages of lung disease in patients with CF and is appropriate in younger patients and to assess disease progression. The imaging findings of abdominal visceral involvement in CF lack specificity(2C). Question 7: How to evaluate the pancreatic function of CF patients? Fecal elastase may be used as the first indicator to assess pancreatic exocrine function in patients with CF (2C). Question 8: How to diagnose hepatic abnormality of CF? CF related liver disease was diagnosed when CF was confirmed and 2 of the following 4 criteria were met: (1) hepatomegaly and/or splenomegaly confirmed by ultrasound; (2) ALT, AST, and GGT on three consecutive occasions above the upper limit of normal on three consecutive occasions for more than 12 months and excluding other causes; (3) had evidence of liver involvement, portal hypertension, or bile duct dilatation by ultrasound; (4) liver biopsy confirmation (focal biliary cirrhosis or multilobular cirrhosis) may be indicated if the diagnosis is suspected(2D). Question 9: How to identify pulmonary exacerbations in patients with CF? Pulmonary exacerbations are indicated when any 4 of the following 12 signs or symptoms are met: increased sputum; new onset haemoptysis or increased haemoptysis; exacerbation of cough; increased dyspnea; malaise, fatigue, or somnolence; body temperature above 38 ℃; anorexia or weight loss; sinus pain or tenderness; increased sinus secretions; new chest signs; FEV 1 ≥10% decline from previous; imaging changes suggestive of pulmonary infection(2D). Question 10: How to diagnose CF related diabetes? Diagnostic criteria for CF related diabetes are the same as those for diabetes in the population(1D). Question 11: How to evaluate the nutritional status of CF patients? Anthropometric parameters reflecting nutritional status should be assessed regularly. And the goal of nutritional assessment is to evaluate and monitor whether pediatric patients are achieving normal standards of growth and development or whether adult patients are maintaining adequate nutritional status(1C). Question 12: Does CF require pathological examination as a diagnostic basis? Pathohistological biopsy is not recommended as a first-line diagnostic method in patients with a suspected diagnosis of CF(1D). Question 13: Do CF patients need long-term macrolides? At least 6 months of azithromycin treatment is recommended for CF patients with chronic PA infection(2A). Question 14: Do CF patients need long-term inhalation of hypertonic saline? Long term treatment with hypertonic saline is recommended for patients with CF(1A). Question 15: Do CF patients need long-term inhalation of Dornase alfa(DNase)? Long term use of DNase is recommended in patients with CF aged 6 years and older(1A). Question 16: Do CF patients need inhalation of mannitol? Inhaled mannitol therapy is recommended for more than 6 months in patients with CF aged 18 years and older when other inhaled treatments are unavailable or intolerable(2A). Question 17: How to deal with PA found in the sputum culture of CF patients? When sputum cultures from patients with CF are positive for PA , it needs to determine the characteristics of the infection first. The purpose for acute infection is to eradicate PA . Chronic colonization does not need to be eradicated, and the main purpose is to reduce the bacterial load and improve symptoms(1A). Question 18: Do CF patients need inhalation of antibiotics? Inhaled antibiotic therapy is recommended for CF patients with PA infection(1A). Question 19: Do CF patients need inhaled or systemic corticosteroids? In patients with CF without asthma or ABPA, routine inhaled or systemic glucocorticoids are not recommended (2A). Question 20: Do CF patients need to inhale bronchodilators? Bronchodilators can be used in the short term to improve symptoms in patients with CF in the presence of airway obstruction, but the long-term benefit is insufficient (2B). Question 21: Do CF patients need expectorant medicine? Patients with CF can take acetylcysteine orally or aerosolized(2A). Question 22: How to deal with acute pulmonary exacerbation in CF patients? Intensive implementation of non-antimicrobial therapy is recommended during pulmonary exacerbations in patients with CF. Antimicrobials with activity against PA were selected for empirical treatment, and the treatment was adjusted according to the results of bacterial culture and drug susceptibility testing. A 21-day long course of anti-infective therapy is not recommended(1B). Question 23: How to treat CF patients with ABPA? Medical therapy is recommended for CF patients with ABPA who meet any of the following criteria: patients with elevated immunoglobulin E levels and concomitant worsening of pulmonary function and/or pulmonary symptoms, or imaging suggesting new infiltrative foci in the chest(1D).Glucocorticoids are recommended for ABPA exacerbations in CF patients without contraindications(2D).Itraconazole should be added if the patient presents with poor response to corticosteroids, recurrence of ABPA, corticosteroid dependence, or corticosteroid toxicity(2D). Question 24: Is lung transplantation recommended for patients with CF? When is it recommended? Patients with CF may be evaluated for lung transplantation when they meet the following criteria after optimal medical therapy: (1) FEV 1 <30% predicted; (2) FEV 1 <40% predicted (<50% predicted in children) with the following: 6-minute walk distance<400 meters; PaCO 2 >50 mmHg(1 mmHg=0.133 kPa); hypoxia at rest or after activity; pulmonary artery pressure measured by cardiotocography>50 mmHg or right heart dysfunction; continued deterioration despite aggressive supplementation of nutritional support; two exacerbations requiring intravenous antibiotic therapy per year; massive hemoptysis (>240 ml) requiring pulmonary artery embolization; presented with pneumothorax; (3) FEV 1 <50% predicted and rapid decline in lung function or rapid worsening of symptoms; (4) Presented with an acute exacerbation requiring positive pressure mechanical ventilation(2C). Question 25: How to deal with pancreatic disease in CF patients? Pancreatic enzyme replacement therapy is recommended in patients with CF pancreatic disease(1A). Question 26: How to deal with hepatobiliary disease in CF patients? Ursodeoxycholic acid is not recommended in asymptomatic patients with CF hepatobiliary disease(2B). Question 27: How to deal with gastrointestinal problems such as acid regurgitation in CF patients? Acid suppression is recommended for CF patients with gastrointestinal symptoms such as acid regurgitation (2B). Question 28: How to deal with CF related diabetes? Insulin therapy is recommended in CF related diabetes(1B). Question 29: How should nutritional support be given to patients with CF? Energy intake in patients with CF is recommended to be 110%-200% of the energy requirement of a healthy person under equivalent physiological conditions. And maintaining adequate protein, appropriate intake of fats, electrolytes, and fat-soluble vitamins are recommanded(1A). Question 30: How should respiratory rehabilitation be performed in patients with CF? Airway clearance therapy and appropriate exercise are recommended for patients with CF(1A). Question 31: What is included in the follow-up of CF patient? Patients with CF should have regular follow-up. Adult patients are recommended to be followed every 3-6 months, and children should be followed more frequently(2A). Question 32: How should CF patients avoid infections? Inpatients and outpatients are recommended to be separated according to microbiota carriage status(1D).Good hand hygiene is recommended for the patients with CF and their contacts(1D).It is recommended that CF patients wear masks in healthcare settings. This may reduce the release of potentially infectious aerosols during coughing (1D).Annual influenza vaccination is recommended for patients with CF>6 months of age and for all family members of patients with CF and all healthcare workers caring for these patients(2D).Palivizumab may be considered for the prevention of respiratory syncytial virus infection in patients with CF under two years of age(2A).

Traumatic brain injury (TBI) remains a major cause of mortality and morbidity, and almost half of these patients are admitted to the intensive care unit. Of those, 10% develop acute kidney injury (AKI) and 2% even need kidney replacement therapy (KRT). Although clinical trials in patients with TBI who have AKI are lacking, some general principles in this population may apply. The present review is an overview on the epidemiology and pathophysiology of AKI in patients with TBI admitted to the intensive care unit who are at risk for or who have developed AKI. A cornerstone in severe TBI management is preventing secondary brain damage, in which reducing the intracranial pressure (ICP) and optimizing the cerebral perfusion pressure (CPP) remain important therapeutic targets. To treat episodes of elevated ICP, osmolar agents such as mannitol and hypertonic saline are frequently administered. Although we are currently awaiting the results of a prospective randomized controlled trial that compares both agents, it is important to realize that both agents have been associated with an increased risk of developing AKI which is probably higher for mannitol compared with hypertonic saline. For the brain, as well as for the kidney, targeting an adequate perfusion pressure is important. Hemodynamic management based on the combined use of intravascular fluids and vasopressors is ideally guided by hemodynamic monitoring. Hypotonic albumin or crystalloid resuscitation solutions may increase the risk of brain edema, and saline-based solutions are frequently used but have a risk of hyperchloremia, which might jeopardize kidney function. In patients at risk, frequent assessment of serum chloride might be advised. Maintenance of an adequate CPP involves the optimization of circulating blood volume, often combined with vasopressor agents. Whether individualized CPP targets based on cerebrovascular autoregulation monitoring are beneficial need to be further investigated. Interestingly, such individualized perfusion targets are also under investigation in patients as a strategy to mitigate the risk for AKI in patients with chronic hypertension. In the small proportion of patients with TBI who need KRT, continuous techniques are advised based on pathophysiology and expert opinion. The need for KRT is associated with a higher risk of intracranial hypertension, especially if osmolar clearance occurs fast, which can even occur in continuous techniques. Precise ICP and CPP monitoring is mandatory, especially at the initiation of KRT., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Introduction: The role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response., Methods: Observational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests., Results: The study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p<0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV 1 , FEV 1 /FVC and FENO, whereas they were FEV 1 /FVC and FENO for mannitol. A FENO value>26ppb, FEV1≤103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value>26ppb was enough to correctly classify 81.5% of mannitol responders., Conclusions: Our study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: This study investigated the risk factors for acute kidney injury (AKI) occurrence in patients with spontaneous intracerebral hemorrhage., Methods: The clinical data of patients with spontaneous intracerebral hemorrhage who were hospitalized in the Department of Intensive Care Medicine of Mingguang People's Hospital from January 2016 to August 2020 were retrospectively analyzed. The patients were divided into AKI group and non-AKI group according to whether the patient had secondary AKI, and the clinical data of the two groups were compared. Logistic regression analysis was used to screen out the risk factors for secondary AKI in patients with spontaneous intracerebral hemorrhage., Results: Three hundred thirty-seven patients were included in this study, whereby 186 males (55.2%) and 151 females (44.8%). A total of 65 patients developed AKI, of whom 44 patients were (67.69%) in stage 1, 12 patients (18.46%) in stage 2, and 9 patients (13.85%) in stage 3. Univariate logistic regression analysis showed that Acute Physiology, Age and Chronic Health Evaluation (APACHE II score), diabetes, chronic kidney disease, fasting blood glucose level and amount of mannitol used were risk factors for AKI in patients with intracerebral hemorrhage. Multivariate logistic regression analysis showed APACHE II score (OR: 1.846, 95% CI: 1.319 to 2.585, p < 0.001), diabetes (OR: 3.609, 95% CI: 1.596 to 8.163, p=0.002) and amount of mannitol use (OR: 3.495, 95% CI: 1.910~3.395, p < 0.001) are the independent risk factors for AKI after intracranial hemorrhage., Conclusion: In summary, APACHE II score, diabetes, and total mannitol use are independent risk factors for AKI in patients with spontaneous intracerebral hemorrhage. It is necessary to monitor renal function frequently in patients with high APACHE II scores and control the amount of mannitol administrated in the prevention of AKI after intracranial hemorrhage. The intervention of the above factors is expected to reduce the risk of secondary AKI.

Hyaluronic acid/mannitol (HA/MN)-based particles were designed as mitomycin c (MMC) delivery vehicles through the crosslinking of 1:0, 3:1, 1:3, and 0:1 mole ratios of HA/MN to investigate their potential use in bladder cancer therapy. The HA/MN-MMC particles prepared by the microemulsion crosslinking method were of 0.5-10 μm size with a zeta potential value of -36.7 mV. The MMC carrier potential of the HA/MN-MMC particles was investigated by changing HA/MN ratios in the particle structure. The MMC loading capacity of neat HA particles was 5.3 ± 1.1 mg/g, whereas HA/MN (1:3) particles could be loaded with about three times more drug, for example, 18.4 ± 0.8 mg/g. The kinetic of MMC drug delivery from the HA/MN-MMC particles were tested in vitro in bladder cancer conditions for example, pH 4.5, 6, and 7.4. The HA-MMC particles released approximately 70% of the loaded drug in 300 h, while 43% of the loaded drug was released from the HA/MN-MMC particles within 600 h under physiological conditions, pH 7.4, 37 °C. The cytotoxicity of HA-based particles on healthy L929 fibroblast cells and HTB-9 human bladder cancer cells was investigated in vitro via MTT tests. Bare MMC inhibited about 90% of L929 fibroblast cells even at 100 μg/mL, but the cell viabilities in the presence of HA-MMC and HA/MN-MMC particles were 85 ± 5 and 109 ± 7% at 1000 μg/mL, respectively. The HA/MN-MMC (1:3) particles at 1000 μg/mL were found capable of destroying half of HTB-9 human bladder cancer cells within 24 h. Interestingly, the same particles at 50 μg/mL destroyed almost all the cancer cells with 8 ± 5% cell viability in 72 h of incubation time. The designed HA/MN-MMC (1:3) particles were found to afford a chemotherapeutic effect on the tumor cancers while reducing the toxicity of MMC against L929 fibroblast cells.

Background: Brain edema is a rare and serious complication of assisted reproductive technology (ART). The increased intracranial pressure and injured brain parenchyma are life-threatening and may even result in death. The pathogenesis may involve increased vascular permeability mediated by vascular endothelial growth factor and other vasoactive substances, including interleukin 6, interleukin 1β, angiotensin II, insulin-like growth factor 1, transforming growth factor β, and the renin-angiotensin system., Case Presentation: We presented a unique case report of a 29-year-old woman developed sudden irritability, blurred consciousness, and vomiting 8 h after oocyte retrieval. Blood examinations showed hyponatremia and cranial computed tomography showed swelling of the brain parenchyma. After therapeutic use of hypertonic saline and mannitol infusion, the patient's consciousness recovered and her neurological state improved., Conclusions: Brain edema is a rare and serious complication of ART. Quick infusion of hypertonic salt solution and mannitol is a key treatment. A good prognosis can be achieved after prompt treatment., (© 2022. The Author(s).)

Sorafenib is an FDA approved chemotherapeutic against hepatocellular carcinoma (HCC) yet associated with various resistance mechanisms. The role of high glucose status on sorafenib action is still to be elucidated. This study clarifies such interaction, taking HepG2 cell lines as HCC models, MALAT1 and H19 as molecular players. HepG2 cell lines were purchased and classified into 8 groups. High glucose status was set by using d-glucose (33 mM) with insulin (1 µM). Mannitol (27.5 mM) was used as a negative osmotic control. Sorafenib was prepared at 15 µM and 20 µM. Cellular viability was assessed with MTT viability assay. Then, with trypan blue viability assay, the results were double checked and HepG2 morphology was examined by optical microscopy. MALAT1 and H19 RQs were assessed by real time PCR (RT-PCR). Results show that in comparison with sorafenib impact on HepG2, high glucose status drops cellular viability to 83.13 % (p < 0.01). With hyperosmolar mannitol, it decreases cellular viability to 72.89 % (p < 0.001). Regarding the molecular impact, hyperosmolar mannitol with sorafenib elevates both MALAT1 and H19 RQs. Yet, high glucose status elevates MALAT1and declines H19 (p < 0.05 and p < 0.001 for MALAT1 and H19 comparisons respectively). Therefore, the impact of high glucose status could be, in part, attributed to the hyperosmolar stress it induces on HepG2. Also, hyperosmolar mannitol, owing to its cytotoxic impact, is recommended for further confirmatory studies either as a separate therapeutic or as an adjuvant to sorafenib., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Traumatic brain injury (TBI) causes mortality and long-term disability among young adults and imposes a notable cost on the healthcare system. In addition to the first physical hit, secondary injury, which is associated with increased intracranial pressure (ICP), is defined as biochemical, cellular, and physiological changes after the physical injury. Mannitol and Hypertonic saline (HTS) are the treatment bases for elevated ICP in TBI. This systematic review and meta-analysis evaluates the effectiveness of HTS in the management of patients with TBI., Methods: This study was conducted following the Joanna Briggs Institute (JBI) methods and PRISMA statement. A systematic search was performed through six databases in February 2022, to find studies that evaluated the effects of HTS, on increased ICP. Meta-analysis was performed using comprehensive meta-analysis (CMA)., Results: Out of 1321 results, 8 studies were included in the systematic review, and 3 of them were included in the quantitative synthesis. The results of the meta-analysis reached a 35.9% (95% CI 15.0-56.9) reduction in ICP in TBI patients receiving HTS, with no significant risk of publication bias (t-value = 0.38, df = 2, p-value = 0.73). The most common source of bias in our included studies was the transparency of blinding methods for both patients and outcome assessors., Conclusion: HTS can significantly reduce the ICP, which may prevent secondary injury. Also, based on the available evidence, HTS has relatively similar efficacy to Mannitol, which is considered the gold standard therapy for TBI, in boosting patients' neurological condition and reducing mortality rates., (© 2022. The Author(s).)

Background: Until now, it has remained difficult for doctors to make an informative decision as to which concentration of hypertonic saline (HTS) is more beneficial for patients with traumatic brain injury (TBI). We therefore investigate the effect of different concentrations of hypertonic saline on mortality and ICP lowering efficacy in this group of patients., Methods: Several databases including Ovid MEDLINE, Ovid EMBASE, PubMed, and Cochrane Central Register of Controlled Trials were searched comprehensively from inception to February 28, 2022. We only included RCTs that compared HTS with different concentrations and mannitol in adult patients with TBI. The main outcome was mortality from any cause. We reported relative risks (RR) and 95% confidence intervals (CIs) from direct meta-analysis and 95% credible intervals (CrIs) from network meta-analysis., Results: Overall, 13 trials containing 593 patients were included in this study. Direct analysis revealed that HTS was associated with decreased risk of all-cause mortality (RR, 1.29; 95% CI: 1.08 to 1.54). In the network meta-analysis, 5% HTS was associated with a significant decrease in all-cause mortality compared with mannitol (RR 0.34, 95% CrI: 0.14 to 0.72). We also found 7.5% HTS was associated with a significant increase in all-cause mortality compared with 5% HTS (RR, 2.87; 95% CrI: 1.00 to 8.99)., Conclusions: Among patients with TBI, the application of 5% HTS was associated with decreased all-cause mortality compared with mannitol and other concentration. Treatments with 10% and 15% HTS was more likely to decrease ICP compared with other fluids. More trials are needed to verify the current findings., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Bacillus anthracis can cause anthrax and is a potential bioterrorism agent. The 2014 Centers for Disease Control and Prevention recommendations for medical countermeasures against anthrax were based on in vitro data and expert opinion. However, a century of previously uncompiled observational human data that often includes treatment and outcomes is available in the literature for analysis., Methods: We reviewed treatment outcomes for patients hospitalized with anthrax. We stratified patients by meningitis status, route of infection, and systemic criteria, then analyzed survival by treatment type, including antimicrobials, antitoxin/antiserum, and steroids. Using logistic regression, we calculated odds ratios and 95% confidence intervals to compare survival between treatments. We also calculated hospital length of stay. Finally, we evaluated antimicrobial postexposure prophylaxis (PEPAbx) using data from a 1970 Russian-language article., Results: We identified 965 anthrax patients reported from 1880 through 2018. After exclusions, 605 remained: 430 adults, 145 children, and 30 missing age. Survival was low for untreated patients and meningitis patients, regardless of treatment. Most patients with localized cutaneous or nonmeningitis systemic anthrax survived with 1 or more antimicrobials; patients with inhalation anthrax without meningitis fared better with at least 2. Bactericidal antimicrobials were effective for systemic anthrax; addition of a protein synthesis inhibitor(s) (PSI) to a bactericidal antimicrobial(s) did not improve survival. Likewise, addition of antitoxin/antiserum to antimicrobials did not improve survival. Mannitol improved survival for meningitis patients, but steroids did not. PEPAbx reduced risk of anthrax following exposure to B. anthracis., Conclusions: Combination therapy appeared to be superior to monotherapy for inhalation anthrax without meningitis. For anthrax meningitis, neither monotherapy nor combination therapy were particularly effective; however, numbers were small. For localized cutaneous anthrax, monotherapy was sufficient. For B. anthracis exposures, PEPAbx was effective., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection., Methods and Analysis: We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4., Ethics and Dissemination: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses., Registration: The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The treatment of rhabdomyolysis remains controversial. Although there is no question that any associated compartment syndrome needs to be identified and released, debate persists regarding the benefit of further therapy including aggressive intravenous fluid resuscitation (IVFR), urine alkalization with bicarbonate, and the use of mannitol. The goal of this practice management guideline was to evaluate the effects of bicarbonate, mannitol, and aggressive intravenous fluids on patients with rhabdomyolysis., Methods: A systematic review and meta-analysis comparing treatments in patients with rhabdomyolysis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of evidence and to create evidence-based recommendations regarding the use of bicarbonate, mannitol, and aggressive IVFR in patients with rhabdomyolysis., Results: A total of 12 studies were identified for analysis. On quantitative analysis, IVFR decreased the incidence of acute renal failure (ARF) and need for dialysis in patients with rhabdomyolysis. Neither bicarbonate nor mannitol administration improved the incidence of acute renal failure and need for dialysis in patients with rhabdomyolysis. Quality of evidence was deemed to be very low, with the vast majority of the literature being retrospective studies., Conclusion: In patients with rhabdomyolysis, we conditionally recommend for aggressive IVFR to improve outcomes of ARF and lessen the need for dialysis. We conditionally recommend against treatment with bicarbonate or mannitol in patients with rhabdomyolysis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The use of mushrooms in medicine is quite old and the first report about the use of genus Agaricus in treatment of ulcers occurred in Byzantine period. This mushroom is widely consumed as food, tea, food supplements, as well as nutraceutical and cosmeceutical applications, being cultivated and appreciated in several countries such as Brazil, Korea, Japan and China., Aim of the Study: This study aimed to characterize the chemical profile and the potential gastroprotective effect of hydroalcoholic extract from Agaricus blazei Murill (HEAb)., Materials and Methods: The extract was chemically characterized by elemental analysis, UPLC-QTOF-MS E , Nuclear Magnetic Resonance (NMR) and high-performance liquid chromatography (HPLC) techniques to elucidate the metabolites present in the extract. The quantification of phenolic compounds and the in vitro antioxidant activities were performed and the gastroprotective effect of this extract was evaluated against ethanol-induced gastric ulcer model. HEAb was administered by gavage at 5, 25 and 50 mg kg -1 and N-acetylcysteine at 300 mg kg -1 (positive control). Furthermore, the pathways of nitric oxide (NO), Cyclic Guanylate Monophosphate (cGMP), prostaglandins (PGs) and the involvement of ATP-sensitive K + Channels were modulated., Results: Mannitol, malic acid, pyroglutamic acid, L-agaritine and L-valine were putatively identified by UPLC-QTOF-MS E in HEAb. In addition, it was possible to identify mannitol by the intense signals in the NMR spectra, being still quantified as the main compound in the extract by HPLC. The contents of total phenols and flavonoids corroborated with the good antioxidant activity of HEAb. This study observed that HEAb at 25 and 50 mg kg -1 had gastroprotection effect demonstrated by the reduction of histopathological parameters and the reduction of mastocytosis in the stomach of mice., Conclusions: In this study was possible to conclude that HEAb has gastroprotective effect related to the involvement of NO and PG pathways in the ethanol-induced gastric ulcer model in mice., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Abstract: To compare the efficacy of mannitol, the first choice of treatment in daily clinical practice for head trauma, and sugammadex, a frequently used neuroanesthesia in recent years. A total of 35 male rats were randomly selected and were divided into 5 groups, each comprising 7 rats. The groups were divided into Group I, sham (n = 7); Group II, control (head trauma, n = 7); Group III, treated with mannitol (head trauma, mannitol 20% 1 g/kg, n = 7); Group IV, treated with sugammadex (head trauma, sugammadex 100 mg/ kg, n = 7); and Group V, treated with mannitol and sugammadex (head trauma, mannitol 20% 1 g/kg and sugammadex 100 mg/kg, n = 7). After the sacrification, histological examination and immu-nohistochemical staining were performed in the brain of all subjects. Mann-Whitney U test was used to evaluate the significance between neuronal density, neuronal nuclei, and activated caspase-3 immunohistochemistry results measured from the prefrontal cortex. Neuronal density showing neuronal viability was observed to significantly increase in Group III compared to Group IV. However, neuronal nuclei immunohistochemistry showing apoptotic neurons also significantly increased. The present study has shown that sugammadex, an agent reversing the effects of neuromuscular blocking agents, has neuroprotective effects and is as effective as mannitol., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Background: Recent randomised clinical trials in bronchiectasis have failed to reach their primary end-points, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis., Methods: We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV 1 ) of ≥100 mL from baseline., Results: Cumulatively the three trials included 984 patients. Changes in FEV 1 , QoL and exacerbations were heterogeneous in all trials analysed. Improvements in QoL were not correlated to changes in FEV 1 in the azithromycin and aztreonam trials (r= -0.17, p=0.1 and r=0.04, p=0.4, respectively) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QoL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV 1 is not a responsive measure in bronchiectasis., Conclusions: Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV 1 is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response, suggesting the need to develop biomarkers to identify responders., Competing Interests: Conflict of interest: O. Sibila has nothing to disclose. Conflict of interest: E. Laserna has nothing to disclose. Conflict of interest: A. Shoemark has nothing to disclose. Conflict of interest: L. Perea has nothing to disclose. Conflict of interest: D. Bilton has nothing to disclose. Conflict of interest: M.L. Crichton reports personal fees from AstraZeneca, outside the submitted work. Conflict of interest: A. De Soyza reports grants, travel support to attend international congresses and lecture fees from AstraZeneca, Bayer, Chiesi, Grifols, GlaxoSmithKline, Insmed, Pfizer, Novartis, Medimmune and Zambon, outside the submitted work. Conflict of interest: W.G. Boersma has nothing to disclose. Conflict of interest: J. Altenburg has nothing to disclose. Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Grifols, Boehringer Ingelheim and Insmed, grants from AstraZeneca and Bayer Healthcare, personal fees from Aradigm, Pfizer and Napp, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Previous randomized-controlled trials have demonstrated that intraoperative intravenous mannitol administration shows no added value on renal functional preservation after partial nephrectomy (PN) in patients with normal renal function. However, the renoprotective effect of mannitol has not been fully evaluated in patients with preoperative chronic kidney disease (CKD). Materials and Methods: This was a retrospective cohort study with propensity score matching. Patients with a preoperative estimated glomerular filtration rate (eGFR) of <60 mL/minute/1.73 m 2 undergoing PN were enrolled in the study between January 2012 and December 2019 in Peking University First Hospital. Participants were divided into two groups: patients who received 25 g of mannitol (group M+) or not (group M-). The primary endpoint was the decreased rate of eGFR at the 6-month follow-up. Results: A total of 244 patients were included in the analysis. After propensity score matching, 80 patients remained in each group. The percentage of decrease from baseline eGFR at postoperative 6-month follow-up showed no difference between the two patient groups (median 11.1 [interquartile range 5.3-25.3] in group M+ vs 12.2 [4.7-21.3] in group M - , median difference -0.7 [95% confidence interval -4.6 to 3.1]; p  = 0.704). Postoperative acute kidney injury, renal replacement therapy during hospitalization, postoperative complications, incidence of >20% decrease from baseline eGFR at 6 months, and dialysis at 6 months showed no difference between the two patient groups. Conclusions: A 25 g dose of mannitol administration during PN failed to provide added value on renal functional preservation in CKD patients.

Background: Saline hydration with addition of mannitol have commonly been the strategy to avoid cisplatin induced acute kidney injury (AKI). While the initial reports demonstrated that mannitol diuresis decreased cisplatin induced renal injury, others have shown renal injury to be worsened., Objective: To compare the risk of AKI in cancer patients receiving high dose cisplatin with and without addition of mannitol., Method: This was an ambispective cohort study based on consecutive sampling at Cipto Mangunkusumo General Hospital (CMGH) and Mochtar Riady Comprehensive Cancer Centre (MRCCC) Siloam Hospitals. The data was obtained from September 2017 to February 2018. The choice of mannitol administration based on attending physician clinical judgement. The primary outcome was increase of serum creatinine more than 0.3 mg/dL or 1.5 times from baseline. Analysis was done by using univariate, bivariate and multivariate logistic regression to obtain crude risk ratio and adjusted risk ratio of cisplatin induced AKI probability caused by mannitol addition on top of usual saline hydration protocol., Result: Data from 110 patients (57.3% male) with a median age of 44.5 years (range 19 to 60 years) were collected; 63 received saline with the addition of mannitol and 47 received saline only. Incidence of AKI were higher in mannitol vs saline only group. Bivariate analysis showed higher probability of post chemotherapy AKI in mannitol group, however it was statistically insignificant (RR 2.168; 95% CI 0.839-5.6; p = 0.094). On multivariate analysis the age adjusted RR was 2.852 (95% CI 0.68-11.96; p = 0.152)., Conclusion: The addition of mannitol to hydration did not reduce the risk of cisplatin induced AKI as compared with saline hydration only. It was also found that risk for acute kidney injury were higher in population ≥ 40 years old., (© 2022. The Author(s).)

Background: Performing a cerebrospinal fluid (CSF) drainage challenge can be used to measure the pressure equalization (PE) ratio, which describes the extent to which CSF drainage can equalize pressure to the height of the external ventricular drain and may serve as a correlate of cerebral edema. We sought to assess whether treatment with mannitol improves PE ratio in patients with severe traumatic brain injury (TBI) with elevated intracranial pressure (ICP)., Methods: We studied consecutive patients with TBI and brain edema on computed tomography scan and an external ventricular drain (EVD), admitted to the neurointensive care unit. PE ratio, defined as ICP prior to CSF drainage minus ICP after CSF drainage divided by ICP prior to CSF drainage minus EVD height, was measured as previously described. Patients were treated with mannitol for raised ICP based on clinical indication and PE ratio measured before and after mannitol administration., Results: We studied 20 patients with severe TBI with raised ICP. Mean ICP prior to mannitol treatment was 29 ± 7 mm Hg. PE ratio rose substantially after mannitol treatment (0.62 ± 0.24 vs. 0.29 ± 0.20, p < 0.0001), indicating an improved ability to drain CSF and equalize ICP with the preset height of the EVD. The combination of mannitol and CSF drainage led to an improved reduction in ICP compared with that seen before mannitol therapy (11 ± 2 mm Hg vs. 6 ± 2 mm Hg, p < 0.01), and led to a decrease in ICP below the 20 mm Hg threshold in 77% of cases., Conclusions: Treatment with mannitol leads to a substantial improvement in PE ratio that reflects the ability to achieve a greater decrease in ICP when CSF drainage is performed after mannitol administration. This preliminary study raises the possibility that PE ratio may be useful to follow response to therapy in patients with cerebral edema and raised ICP. Further studies to determine whether PE ratio may serve as an easily obtained and clinically useful surrogate marker for the extent of brain edema are warranted., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: Nephrotoxicity is a major dose-limiting toxicity among patients with cancer who were treated with cisplatin. Although no standard approach is available to prevent cisplatin-induced nephrotoxicity, administering intravenous isotonic saline is recommended. Additionally, mannitol combined with hydration has been evaluated, but none of them have been established. Our study aimed to determine the efficacy of mannitol combined hydration to prevent cisplatin-induced nephrotoxicity., Patients and Methods: This study was a phase II, randomized, placebo-controlled design. All patients with solid cancers who were treated with cisplatin (n = 48) were randomly assigned to receive either placebo (n = 25) or 20 g of mannitol (n = 23) after completing 2 L of prehydration and receiving cisplatin. Serum creatinine, blood urea nitrogen, electrolyte, and glomerular filtration rate (GFR) were measured at baseline and days 2 and 7. Moreover, GFR was calculated based on the 24-hour urine creatinine clearance rate to assess renal function at baseline and 48 hours after receiving cisplatin. Severity of nausea and vomiting was evaluated using Common Terminology Criteria for Adverse Events., Results: No difference was found regarding baseline characteristics between the two groups. Seven of 23 patients (37.4%) in the mannitol group and 10 of 25 patients (40%) in the placebo group increased serum creatinine level ≥ 0.3 mg/dL at 48 hours after intervention ( P value = .48). Patients receiving mannitol exhibited significantly lower incidence of 24-hour urine GFR below 60 mL/min/1.73 m than those in the placebo group (13.6% v 48.0% in the placebo group; P value = .012). Univariate analysis showed the greatest benefit for administering mannitol among patients receiving cisplatin > 80 mg/m 2 , or patients receiving concomitant radiation., Conclusion: Mannitol combined with hydration significantly prevented cisplatin-induced nephrotoxicity. Additionally, mannitol should be particularly considered among patients with cancer, treated with cisplatin > 80 mg/m 2 , or patients receiving concomitant radiation., Competing Interests: Panot SainamthipStock and Other Ownership Interests: Ladprao General Hospital Naiyarat PrasongsookConsulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Roche, Novartis, Bristol Myers Squibb/CelgeneTravel, Accommodations, Expenses: AstraZeneca, RocheNo other potential conflicts of interest were reported.

Importance: Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol., Objectives: To characterize current use of hyperosmolar agents in pediatric severe traumatic brain injury and assess whether HTS or mannitol is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP)., Design, Setting, and Participants: In this comparative effectiveness research study, 1018 children were screened and 18 were excluded; 787 children received some form of hyperosmolar therapy during the ICP-directed phase of care, with 521 receiving a bolus. Three of these children were excluded because they had received only bolus administration of both HTS and mannitol in the same hour, leaving 518 children (at 44 clinical sites in 8 countries) for analysis. The study was conducted from February 1, 2014, to September 31, 2017, with follow-up for 1 week after injury. Final analysis was performed July 20, 2021., Interventions: Boluses of HTS and mannitol were administered., Main Outcomes and Measures: Data on ICP and CPP were collected before and after medication administration. Statistical methods included linear mixed models and corrections for potential confounding variables to compare the 2 treatments., Results: A total of 518 children (mean [SD] age, 7.6 [5.4] years; 336 [64.9%] male; 274 [52.9%] White) were included. Participants' mean (SD) Glasgow Coma Scale score was 5.2 (1.8). Bolus HTS was observed to decrease ICP and increase CPP (mean [SD] ICP, 1.03 [6.77] mm Hg; P < .001; mean [SD] CPP, 1.25 [12.47] mm Hg; P < .001), whereas mannitol was observed to increase CPP (mean [SD] CPP, 1.20 [11.43] mm Hg; P = .009). In the primary outcome, HTS was associated with a greater reduction in ICP compared with mannitol (unadjusted β, -0.85; 95% CI, -1.53 to -0.19), but no association was seen after adjustments (adjusted β, -0.53; 95% CI, -1.32 to 0.25; P = .18). No differences in CPP were observed. When ICP was greater than 20 mm Hg, greater than 25 mm Hg, or greater than 30 mm Hg, HTS outperformed mannitol for each threshold in observed ICP reduction (>20 mm Hg: unadjusted β, -2.51; 95% CI, -3.86 to -1.15, P < .001; >25 mm Hg: unadjusted β, -3.88; 95% CI, -5.69 to -2.06, P < .001; >30 mm Hg: unadjusted β, -4.07; 95% CI, -6.35 to -1.79, P < .001), with results remaining significant for ICP greater than 25 mm Hg in adjusted analysis., Conclusions and Relevance: In this comparative effectiveness research study, bolus HTS was associated with lower ICP and higher CPP, whereas mannitol was associated only with higher CPP. After adjustment for confounders, both therapies showed no association with ICP and CPP. During ICP crises, HTS was associated with better performance than mannitol.

Aim: To quantify the effects of 3% hypertonic saline (HTS) boluses on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in children., Methods: A retrospective study of patients admitted to a regional neurosurgical children's intensive care unit., Results: A total of 156 HTS boluses were given to children with traumatic brain injury. ICP decreased 6 mmHg (P < 0.01) and CPP increased 4 mmHg (P = 0.003) 1-h post-bolus. Effects persisted for 3 h post-dose ICP was 5 mmHg lower) and 4 h post-bolus CPP was 3 mmHg higher. ICP change was not associated with pre-bolus serum sodium concentration., Conclusions: Hypertonic saline 3% at 5 mL/kg is an effective osmolar therapy for reducing ICP and increasing CPP in children for up to 3 h. '53-53' is a suitable guide - 5 mL/kg of 3% HTS will on average decrease ICP by at least 5 mmHg for 3 h. Pre-bolus serum sodium concentration is not correlated with effect size., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Sodium lactate (SL) has been described as an efficient therapy in treating raised intracranial pressure (ICP). However, the precise mechanism by which SL reduces intracranial hypertension is not well defined. An antiedematous effect has been proposed but never demonstrated. In this context, the involvement of chloride channels, aquaporins, or K-Cl cotransporters has also been suggested, but these mechanisms have never been assessed when using SL., Methods: In a rat model of traumatic brain injury (TBI), we compared the effect of SL versus mannitol 20% on ICP, cerebral tissue oxygen pressure, and brain water content. We attempted to clarify the involvement of chloride channels in the antiedematous effects associated with lactate therapy in TBI., Results: An equimolar single bolus of SL and mannitol significantly reduced brain water content and ICP and improved cerebral tissue oxygen pressure 4 h after severe TBI. The effect of SL on brain water content was much longer than that of mannitol and persisted at 24 h post TBI. Western blot and immunofluorescence staining analyses performed 24 h after TBI revealed that SL infusion is associated with an upregulation of aquaporin 4 and K-Cl cotransporter 2., Conclusions: SL is an effective therapy for treating brain edema after TBI. This study suggests, for the first time, the potential role of chloride channels in the antiedematous effect induced by exogenous SL., (© 2021. The Author(s).)

Purpose: Hypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP)., Methods: This study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were "half-molar sodium lactate", "mannitol", "cerebral edema or brain swelling", and "severe traumatic brain injury". The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3., Results: From 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09)., Conclusion: Half-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium., (Copyright © 2021 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Objective. Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. Methods. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol ® ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively. Subsequently, KT was performed after unilateral right nephrectomy. Study outcomes included markers for kidney function, oxidative stress, lipid peroxidation, and endothelial cell damage. PCR analysis for oxidative stress and apoptosis-related gene panels as well as immunohistochemistry were performed. Results. RLX upregulated SOD2 and NFKB expression to 135% ( p = 0.042) and 125% ( p = 0.019), respectively, while RIPK1 expression was downregulated to 82% ( p = 0.016) of corresponding controls. Further RLX significantly downregulated RIPK1 and MLKL expression and decreased the number of Caspase 3- and MPO-positive cells in grafts after SCS. Conclusions. RLX supplemented Custodiol ® significantly decreased IRI via both antioxidant and anti-apoptotic mechanisms. Clinical trials are warranted to implement synthetic human RLX as a novel additive to preservation solutions against IRI.