Effects of correcting metabolic acidosis on muscle mass and functionality in chronic kidney disease:a systematic review and meta-analysis

Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the effects of correcting metabolic acidosis on nutritional status in patients with CKD in a systematic review and meta-analysis. A search was conducted in MEDLINE and the Cochrane Library from inception to June 2023. Study selection, bias assessment, and data extraction were independently performed by two reviewers. The Cochrane risk of bias tool was used to assess the quality of individual studies. We applied random effects meta-analysis to obtain pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). We retrieved data from 12 intervention studies including 1995 patients, with a mean age of 63.7 ± 11.7 years, a mean estimated glomerular filtration rate of 29.8 ± 8.8 mL/min per 1.73 m2, and 58% were male. Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl-binding polymer, with placebo. The mean change in serum bicarbonate was +3.6 mEq/L in the intervention group and +0.4 mEq/L in the control group. Correcting metabolic acidosis significantly improved muscle mass assessed by mid-arm muscle circumference (SMD 0.35 [95% CI 0.16 to 0.54], P &lt; 0.001) and functionality assessed with the sit-to-stand test (SMD −0.31 [95% CI −0.52 to 0.11], P = 0.003). We found no statistically significant effects on dietary protein intake, handgrip strength, serum albumin and prealbumin concentrations, and blood urea nitrogen. Correcting metabolic acidosis in patients with CKD improves muscle mass and physical function. Correction of metabolic acidosis should be considered as part of the nutritional care for patients with CKD.</p

Isolated Limb Perfusion and External Beam Radiotherapy for Soft Tissue Sarcomas of the Extremity: Long-Term Effects on Normal Tissue According to the LENT-SOMA Scoring System

BACKGROUND: With the combined treatment procedure of isolated limb perfusion (ILP), delayed surgical resection and external beam radiotherapy (EBRT) for locally advanced soft tissue sarcomas (STS) of the extremities, limb salvage rates of more than 80% can be achieved. However, long-term damage to the healthy surrounding tissue cannot be prevented. We studied the late effects on the normal tissue using the LENT-SOMA scoring system. PATIENTS AND METHODS: A total of 32 patients-median age 47 (range 14-71) years-were treated for a locally advanced STS with ILP, surgical resection and often adjuvant 60-70 Gy EBRT. After a median follow-up of 88 (range 17-159) months, the patients were scored, using the LENT-SOMA scales, for the following late tissue damage: muscle/soft tissue, peripheral nerves, skin/subcutaneous tissue and vessels. RESULTS: According to the individual SOM parameters of the LENT-SOMA scales, 20 patients (63%) scored grade-3 toxicity on one or more separate items, reflecting severe symptoms with a negative impact on daily activities. Of these patients, 3 (9%) even scored grade-4 toxicity on some of the parameters, denoting irreversible functional damage necessitating major therapeutic intervention. CONCLUSIONS: In evaluating long-term morbidity after a combined treatment procedure for STS of the extremity, using modified LENT-SOMA scores, two-thirds of patients were found to have experienced serious late toxic effects

Histamine, a vasoactive agent with vascular disrupting potential, improves tumour response by enhancing local drug delivery

Tumour necrosis factor (TNF)-based isolated limb perfusion (ILP) is an approved and registered treatment for sarcomas confined to the limbs in Europe since 1998, with limb salvage indexes of 76%. TNF improves drug distribution in solid tumours and secondarily destroys the tumour-associated vasculature (TAV). Here we explore the synergistic antitumour effect of another vasoactive agent, histamine (Hi), in doxorubicin (DXR)-based ILP and evaluate its antivascular effects on TAV. We used our well-established rat ILP model for in vivo studies looking at tumour response, drug distribution and effects on tumour vessels. In vitro studies explored drug interactions at cellular level on tumour cells (BN-175) and Human umbilical vein endothelial cells (HUVEC). There was a 17% partial response and a 50% arrest in tumour growth when Hi was combined to DXR, without important side effects, against 100% progressive disease with DXR alone and 29% arrest in tumour growth for Hi alone. Histology documented an increased DXR leakage in tumour tissue combined to a destruction of the TAV, when Hi was added to the ILP. In vitro no synergy between the drugs was observed. In conclusion, Hi is a vasoactive drug, targeting primarily the TAV and synergises with different chemotherapeutic agents

Isolated limb perfusion for unresectable extremity cutaneous squamous cell carcinoma; an effective limb saving strategy

Background: A small minority of patients present with locally advanced cutaneous Squamous Cell Carcinoma (cSCC). The aim of this study was to evaluate the effectiveness of Tumour necrosis factor α (TNF) and melphalan based isolated limb perfusion (TM-ILP) as a limb saving strategy for locally advanced extremity cSCC. Methods: A retrospective search from prospectively maintained databases, at two tertiary referral centers, was performed to identify patients treated with TM-ILP for locally advanced cSSC of an extremity between 2000 and 2015. Results: A total of 30 patients treated with TM-ILP for cSCC were identified, with a median age of 71 years (36–92) and 50% female. Response could not be evaluated in 3 patients. After a median follow up of 25 months, the overall response rate was 81% (n = 22), with 16 patients having a complete response (CR, 59%). A total of 7 patients developed local recurrence, with a median time to recurrence of 9 months (Interquartile Range 7–10). Progressive disease was observed in 5 patients (19%). Limb salvage rate was 80%. The overall 2-year survival was 67%. Conclusions: TM-ILP should be considered as an option in patients with locally advanced cSCC in specialised centers, resulting in a high limb salvage rate

Mastery Profiling through Entity Linking: to Support Project Team Formation in Higher Education

Computer-supported group formation enables educators to assign students to project teams. The focus in this paper is placed on gathering data about student attributes that are relevant in the context of specific course projects. We developed a method that automatically produces learner models from existing documents, by linking students to topics and estimating the levels of skill, knowledge, and interest that students have in these topics. The method is evaluated in an experiment with student participants, wherein its performance is measured on two levels. Our results demonstrate that it is possible to link students to topics with high precision, but suggest that estimating mastery levels is a more challenging task

Impact of infantile short bowel syndrome on long-term health-related quality of life: a cross-sectional study

Studies on the long-term effects of short bowel syndrome (SBS) on the quality of life are scarce. Therefore, we determined health-related quality of life (HRQoL) in children and adolescents with a history of infantile SBS compared with that of same-aged controls drawn from the general population. Cross-sectional assessment (2005-2007) of HRQoL in children with a history of infantile SBS treated in their first year of life, born between 1987 and 2002, using generic HRQoL measures was performed. Children aged 5 to 18 years and their parents filled out the Pediatric Quality of Life Inventory. Differences in scores between subjects and controls were analyzed using independent sample t tests. Thirty-one children with a history of SBS (19 girls and 12 boys; mean age, 11.8 ± 4.2 years) participated, giving an overall response rate of 70%. The children and their parents reported significantly lower HRQoL than 275 healthy age-matched children and their parents (P <.05). Children with a history of infantile SBS have a lower HRQoL than healthy age-matched controls. This difference lasts beyond childhood and way beyond the period of intestinal rehabilitation early in life. These findings highlight the need for targeted interventions to address these dimensions of impaired HRQo

Comment on Moriconi et al. Very-Low-Calorie Ketogenic Diet as a Safe and Valuable Tool for Long-Term Glycemic Management in Patients with Obesity and Type 2 Diabetes. Nutrients 2021, 13, 758

With interest, we have read the article of Moriconi et al. [...

Energy expenditure and feeding practices and tolerance during the acute and late phase of critically ill COVID-19 patients

Background & aims: Different metabolic phases can be distinguished in critical illness, which influences nutritional treatment. Achieving optimal nutritional treatment during these phases in critically ill patients is challenging. COVID-19 patients seem particularly difficult to feed due to gastrointestinal problems. Our aim was to describe measured resting energy expenditure (mREE) and feeding practices and tolerance during the acute and late phases of critical illness in COVID-19 patients.  Methods: Observational study including critically ill mechanically ventilated adult COVID-19 patients. Indirect calorimetry (Q-NRG+, Cosmed) was used to determine mREE during the acute (day 0–7) and late phase (>day 7) of critical illness. Data on nutritional intake, feeding tolerance and urinary nitrogen loss were collected simultaneously. A paired sample t-test was performed for mREE in both phases.  Results: We enrolled 21 patients with a median age of 59 years [44–66], 67% male and median BMI of 31.5 kg/m2 [25.7–37.8]. Patients were predominantly fed with EN in both phases. No significant difference in mREE was observed between phases (p = 0.529). Sixty-five percent of the patients were hypermetabolic in both phases. Median delivery of energy as percentage of mREE was higher in the late phase (94%) compared to the acute phase (70%) (p = 0.001). Urinary nitrogen losses were significant higher in the late phase (p = 0.003).  Conclusion: In both the acute and late phase, the majority of the patients were hypermetabolic and fed enterally. In the acute phase patients were fed hypocaloric whereas in the late phase this was almost normocaloric, conform ESPEN guidelines. No significant difference in mREE was observed between phases. Hypermetabolism in both phases in conjunction with an increasing loss of urinary nitrogen may indicate that COVID-19 patients remain in a prolonged acute, catabolic phase