-
1.
The effects of Bacillus coagulans MTCC 5856 on functional gas and bloating in adults: A randomized, double-blind, placebo-controlled study.
Majeed, M, Nagabhushanam, K, Paulose, S, Arumugam, S, Mundkur, L
Medicine. 2023;102(9):e33109
-
-
-
Free full text
-
Plain language summary
The reasons for bloating and feelings of stomach discomfort are not fully understood and it is thought that they may be caused by several factors. Amongst these is the possibility that small intestinal bacterial overgrowth (SIBO) and gut microbiota alterations play a role in the development of bloating. Many therapies exist for the symptomatic relief of bloating, however probiotics may be effective for the relief of bloating due to the role of gut microbiota in its development. This randomised control trial of 66 individuals with abdominal bloating, discomfort, and gas aimed to determine the effectiveness of a gut bacteria strain known as Bacillus coagulans MTCC 5856 on feelings of gas and bloating. The results showed that supplementation with B. coagulans MTCC 5856 for 4 weeks relieved feelings of bloating, burping, and gas. It was concluded that B. coagulans MTCC 5856 supplementation was effective at relieving gas and bloating and may be a safe approach for individuals who experience these symptoms. This study could be used by healthcare professionals to recommend B. coagulans MTCC 5856 as a safe and effective therapy for individuals who suffer from gastrointestinal problems such as gas, bloating and stomach discomfort.
Abstract
BACKGROUND Gut microbiome dysbiosis is a major cause of abdominal gas, bloating, and distension. Bacillus coagulans MTCC 5856 (LactoSpore) is a spore-forming, thermostable, lactic acid-producing probiotic that has numerous health benefits. We evaluated the effect of Lacto Spore on improving the clinical symptoms of functional gas and bloating in healthy adults. METHODS Multicenter, randomized, double-blind, placebo-controlled study at hospitals in southern India. Seventy adults with functional gas and bloating with a gastrointestinal symptom rating scale (GSRS) indigestion score ≥ 5 were randomized to receive B coagulans MTCC 5856 (2 billion spores/day, N = 35) or placebo (N = 35) for 4 weeks. Changes in the GSRS-Indigestion subscale score for gas and bloating and global evaluation of patient's scores from screening to the final visit were the primary outcomes. The secondary outcomes were Bristol stool analysis, brain fog questionnaire, changes in other GSRS subscales, and safety. RESULTS Two participants from each group withdrew from the study and 66 participants (n = 33 in each group) completed the study. The GSRS indigestion scores changed significantly (P < .001) in the probiotic group (8.91-3.06; P < .001) compared to the placebo (9.42-8.43; P = .11). The median global evaluation of patient's scores was significantly better (P < .001) in the probiotic group (3.0-9.0) than in the placebo group (3.0-4.0) at the end of the study. The cumulative GSRS score, excluding the indigestion subscale, decreased from 27.82 to 4.42% (P < .001) in the probiotic group and 29.12 to 19.33% (P < .001) in the placebo group. The Bristol stool type improved to normal in both the groups. No adverse events or significant changes were observed in clinical parameters throughout the trial period. CONCLUSIONS Bacillus coagulans MTCC 5856 may be a potential supplement to reduce gastrointestinal symptoms in adults with abdominal gas and distension.
-
2.
Efficacy and dose response of Lactiplantibacillus plantarum in diarrhea-predominant irritable bowel syndrome.
Martoni, CJ, Srivastava, S, Damholt, A, Leyer, GJ
World journal of gastroenterology. 2023;29(28):4451-4465
-
-
-
-
Free full text
Plain language summary
Probiotics are microorganisms that have been shown in previous research to improve symptoms of diarrhoea-predominant irritable bowel syndrome (IBS-D). This randomised control trial of 307 individuals with IBS-D aimed to determine the tolerability and efficacy of varying doses of the microbiota Lactiplantibacillus plantarum. The results showed that the severity of symptoms improved with L. plantarum regardless of whether individuals were given a high or low dose. Improvements were seen as soon as 28 days following supplementation. Abdominal pain severity, duration, bloating, bowel movements, and quality of life were all improved. Individuals in the study largely tolerated the supplement, with only a few occurrences of nausea and vomiting. It was concluded that L. plantarum is effective and safe for improving symptoms associated with IBS-D. This study could be used by healthcare professionals to recommend L. plantarum supplementation to individuals with hard to treat or persistent IBS-D.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This randomised, double-blind, placebo controlled, multi-centre, parallel-arm and dose-ranging study showed that L. plantarum may be a strong candidate for the management of IBS-D symptoms and associated mental health effects.
- L. plantarum may be of particular benefit to individuals who are suffering from stress because of IBS-D.
- L. plantarum is well tolerated and may be of benefit to individuals who have ceased pharmaceutical treatments as a result of side-effects.
Evidence Category:
-
X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
-
B: Systematic reviews including RCTs of limited number
-
C: Non-randomized trials, observational studies, narrative reviews
-
D: Case-reports, evidence-based clinical findings
-
E: Opinion piece, other
Summary Review:
Introduction
This study aimed to determine the tolerability and efficacy of varying supplemental doses of Lactiplantibacillus plantarum (Lpla33) in adults with irritable bowel syndrome of the diarrhoea predominant subtype (IBS-D).
Methods
This randomised, double blind, placebo-controlled trial recruited 307 females and males aged 18-70 years with IBS-D based upon the Rome IV diagnostic criteria with Bristol Stool Scale stools of type 6 or 7.
Individuals were randomised to receive an eight-week intervention in one of three study groups: Group 1B: Lpla33 at 1 × 109 vs group 10B: 1x1010 colony forming units (CFU) per day vs placebo.
Results
- Improvement was seen in the primary outcome of IBS-D symptom severity (IBS-SSS) with both Lpla33 doses compared to placebo at the end of the trial (P=<0.001).
- Improvements with both doses compared to placebo were seen as quickly as 28 days (P=<0.01).
- At the end of the study the higher dose Lpla33 was more effective at improving IBS-SSS compared to the lower dose (P=<0.05).
- Improvements to IBS remission or mild IBS were seen in 48.1% in group 1B, 72.6% in group 10B and only 11.1% of placebo (P=<0.001).
- Specific improvements were seen in 10B group compared to placebo in abdominal pain severity and duration, abdominal distension, bowel habits, and quality of life (QoL) (P=<0.001).
- Post-hoc analysis showed that supplementation prevented symptom development compared to placebo with 2.9% of group 1B, 2.1% of group 10B and 18.2% of placebo individuals reporting increased symptom severity (P=<0.001).
- QoL and perceived stress were improved with supplementation compared to placebo (P=<0.001 for both), with the higher dose being more beneficial than the lower dose in QoL (P=<0.001).
- Compliance to Lpla33 was comparable to placebo (P=>0.05), with adverse events related to the supplement including nausea and vomiting.
Conclusion
- L. plantarum at doses of 1 × 109 and 1 × 1010 CFU/day is a well-tolerated and efficacious therapy for the improvement of symptoms related to IBS-D, with benefits seen as quickly as 28 days after commencing supplementation.
- Symptoms such as abdominal pain severity and duration, QoL and perceived stress may all be improved.
- Stool normalisation may be seen in certain individuals.
Clinical practice applications:
- L. plantarum supplementation may be of benefit to the management and improvement of symptoms in individuals with IBS-D.
- Improvements may be seen physically and in mental health parameters.
- Metronidazole (400mg/day) was given as a rescue medication for individuals with severe pain and frequent loose stools and should be considered when interpreting results.
Considerations for future research:
- The authors concluded that future research should focus on understanding the mechanisms of action that may be involved.
- Studying the role of diet on the microbial community and metabolite profiles in IBS-D may be of interest.
Abstract
BACKGROUND Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D); however, the certainty of evidence is low. Well-powered randomized controlled dose-ranging trials are warranted on promising single-strain candidates. AIM: To investigate the clinical efficacy of Lactiplantibacillus plantarum (L. plantarum) Lpla33 (DSM34428) in adults with IBS-D. METHODS This is a randomized, double-blind, placebo-controlled, multi-center, and dose-ranging study. Three hundred and seven adults, 18-70 years of age, with IBS-D, according to Rome IV criteria, were allocated (1:1:1) to receive placebo or L. plantarum Lpla33 at 1 × 109 (1B) or 1 × 1010 (10B) colony-forming units/d over an 8-wk intervention period. The primary outcome was the change in IBS severity scoring system (IBS-SSS) total score after 8 wk, while secondary and exploratory outcomes included abdominal pain severity, IBS related quality of life, stool and microbial profile, and perceived stress. RESULTS IBS-SSS was significantly reduced, after 8 wk, in participants receiving L. plantarum 1B (-128.45 ± 83.30; P < 0.001) and L. plantarum 10B (-156.77 ± 99.06; P < 0.001), compared to placebo (-58.82 ± 74.75). Further, a dose-ranging effect was observed, with a greater absolute reduction in the L. plantarum 10B group (P < 0.05). A reduction in sub-scores related to abdominal pain, abdominal distension, bowel habits, and quality of life was observed in both L. plantarum groups compared to placebo (P < 0.001). Further, 62.5% and 88.4% of participants administered L. plantarum 1B and 10B, respectively, were classified as stool consistency responders based on a reduction in diarrheal stool form, as compared to 26.3% in the placebo group (P < 0.001). In contrast, no significant shifts were observed in microbial diversity. CONCLUSION L. plantarum Lpla33 (DSM34428) is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.
-
3.
Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study.
Wang, S, Ma, P, Zhang, S, Song, S, Wang, Z, Ma, Y, Xu, J, Wu, F, Duan, L, Yin, Z, et al
Diabetologia. 2020;63(10):2102-2111
-
-
-
Free full text
-
Plain language summary
Hyperglycaemia was a risk factor for mortality from severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and is an independent risk factor for lower respiratory tract infection and poor prognosis. The aim of this retrospective study of 605 patients without previously diagnosed diabetes was to examine the association between fasting blood glucose (FBG) on admission and the 28-day in hospital mortality of COVID-19 patients. Patients with a FBG level of 7.0mmol/l or over had more than double the risk of dying than those with a level of 6.0mmol/l or less. Other risk factors for mortality included age, being male, and severity of pneumonia at admission. Compared with patients whose FBG was 6.0mmol/l or lower at admission, patients with FBG of 7.0 mmol/l and above had a 3.99 times higher risk of in-hospital complications, whilst those with FBG of 6.1–6.9 mmol/l had a 2.61 times higher risk of complications. The authors conclude that glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes.
Abstract
AIMS/HYPOTHESIS Hyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes. METHODS We conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years). RESULTS Six hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1-2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3-4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1-6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively. CONCLUSIONS/INTERPRETATION FBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. Graphical abstract.
-
4.
Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.
Cariou, B, Hadjadj, S, Wargny, M, Pichelin, M, Al-Salameh, A, Allix, I, Amadou, C, Arnault, G, Baudoux, F, Bauduceau, B, et al
Diabetologia. 2020;63(8):1500-1515
-
-
-
Free full text
-
Plain language summary
People with diabetes have an increased risk for infections, especially influenza and pneumonia, and also appear to be particularly vulnerable to develop severe disease or die from Covid-19. The aim of this multicentre observational study from France was to determine clinical and biological features in patients with diabetes and hospitalised for Covid-19. A total of 1317 patients were analysed, with the main outcomes being intubation for mechanical ventilation (reached by 267 patients, 29%) or death (140 patients, 10.6%) within 7 days of being admitted to hospital. HbA1C, as a marker of how well controlled the diabetes was, was not associated with either risk of death or need for mechanical ventilation. When other factors were taken into account, only body mass index was associated with risk of ventilation, whilst age, history of microvascular or macrovascular complications (injury to small or large blood vessels), and treated obstructive sleep apnoea were found to be independently associated with the risk of death. Of clinical and blood test parameters on admission, difficulty breathing, lymphopaenia (low levels of specific white blood cells), and increased AST (marker of liver function) and CRP (marker of inflammation) were independent factors for predicting severity of the course of COVID-19.
Abstract
AIMS/HYPOTHESIS Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION clinicaltrials.gov NCT04324736.
-
5.
Longitudinal Study of the Psoriasis-Associated Skin Microbiome during Therapy with Ustekinumab in a Randomized Phase 3b Clinical Trial.
Loesche, MA, Farahi, K, Capone, K, Fakharzadeh, S, Blauvelt, A, Duffin, KC, DePrimo, SE, Muñoz-Elías, EJ, Brodmerkel, C, Dasgupta, B, et al
The Journal of investigative dermatology. 2018;138(9):1973-1981
-
-
-
Free full text
Plain language summary
Chronic plaque psoriasis is an immune-mediated disease of the skin and joints. A growing appreciation of the role of the innate immune system in psoriasis pathogenesis stems from the prominent role of inflammatory cytokines and cells associated with innate immunity in the disease and associations observed between psoriasis and genetic variations involved in innate immunity. The aim of this study was to assess changes of the skin microbiome in the setting of a longitudinal phase 3b study of patients receiving up to 2 years of ustekinumab therapy. Results show that prior to treatment, there were minor, body-site specific differences in microbial diversity and composition when comparing lesional with non-lesional skin. Microbial heterogeneity was greater in lesional skin than non-lesional skin. During ustekinumab treatment, the composition of microbiota diverged further between lesional and non-lesional skin across body sites. The divergence observed between lesional and non-lesional skin during ustekinumab treatment varied by body site. Authors conclude that their findings may help inform future study design and it may also have medically relevant implications for diagnostics and therapeutics involving the skin microbiome.
Abstract
Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a phase 3b clinical trial. By sequencing the bacterial 16S ribosomal RNA gene from skin swab samples obtained at six anatomical sites, we identified minor, site-specific differences in microbial diversity and composition between pretreatment lesional and nonlesional skin. During therapy, microbial communities within lesional and nonlesional skin diverged, and body-site dispersion increased, reflecting microbial skin site-specificity. Microbiota demonstrated greater pretreatment heterogeneity in psoriatic lesions than in nonlesional skin, and variance increased as treatment progressed. Microbiota colonizing recurrent lesions did not overlap with pretreatment lesional microbiota, suggesting colonization patterns varied between initial and recurrent psoriatic lesions. While plaque psoriasis does not appear to be associated with specific microbes and/or microbial diversity, this large dataset provides insight into microbial variation associated with (i) disease in different body locations, (ii) initial versus recurrent lesions, and (iii) anti-IL12/23 therapy.
-
6.
Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.
Laharie, D, Bourreille, A, Branche, J, Allez, M, Bouhnik, Y, Filippi, J, Zerbib, F, Savoye, G, Vuitton, L, Moreau, J, et al
Gut. 2018;67(2):237-243
-
-
-
Free full text
-
Plain language summary
Intravenous steroids are the first-line therapy for ulcerative colitis (UC) patients who are hospitalised during a severe UC flare-up. In the 40% of patients who don’t respond to steroids, the drugs ciclosporin and infliximab have been found to be efficient in preventing surgery to remove part or all of the colon, but there is a lack of data on the long-term outcomes of using these medications in UC patients. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. Between 2007 and 2010, 115 patients with UC that did not respond to steroids were randomised to receive ciclosporin or infliximab in association with azathioprine. Patients were followed to January 2015 or death. After a median follow-up of 5.4 years, colectomy-free survival rates at 1 and 5 years were, respectively, 70.9% and 61.5% in patients who received ciclosporin and 69.1% and 65.1% in those who received infliximab. Long-term colectomy-free survival was independent from initial treatment. However, a higher proportion of patients initially treated with ciclosporin needed a new treatment compared with those who received infliximab first. The researchers concluded that these results further confirm a similar efficacy and good safety profiles of both drugs.
Abstract
OBJECTIVE Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.
-
7.
Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: The EverExt study.
Pizzuti, L, Marchetti, P, Natoli, C, Gamucci, T, Santini, D, Scinto, AF, Iezzi, L, Mentuccia, L, D'Onofrio, L, Botticelli, A, et al
Scientific reports. 2017;7(1):10597
-
-
-
Free full text
Plain language summary
Literature shows that hyperglycaemia is amongst the most common grade 3 or 4 drug-related adverse events in breast cancer patients. The aim of the study was to investigate the role of anthropometrics and biomarkers of glucose metabolism on treatment outcomes in advanced breast cancer patients. The study is an observational study that recruited 102 postmenopausal women, aged at least 18 years, who were diagnosed with advanced breast cancer and treated with everolimus and exemestane. Results indicate a significant trend towards increasing fasting glucose and decreasing BMI in the overall study population. Furthermore, significant evidence also shows that lower levels of fasting glucose is associated with better outcomes. Authors conclude that their study showed a predictive role of fasting glucose and BMI on treatment outcomes, longer progression free survival and clinical benefit rates (percentage of patients with shrinking tumours or stable disease for at least 6 months).
Abstract
Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms.