Introduction

Obesity remains a global health challenge, with long‑term weight management often limited by metabolic adaptation and poor dietary adherence. Tirzepatide—a dual glucose‑dependent insulinotropic polypeptide (GIP) and glucagon‑like peptide‑1 (GLP‑1) receptor agonist— has shown substantial and durable weight‑reducing effects across its phase‑3 clinical‑development program. Although high‑protein diets (HPD) can preserve lean mass and enhance satiety, few real‑world data address their combined use with tirzepatide. We therefore conducted a retrospective study to assess whether HPD associated with tirzepatide aid to preserve lean mass magnifying weight‑loss outcomes compared to a standard‑protein diet (SPD).

Aims & Methods

We performed a single‑centre, retrospective analysis of adults with obesity or overweight plus at least one metabolic comorbidity who initiated once‑weekly subcutaneous tirzepatide 2.5 mg between February and April 2025. All patients received dietary counseling that prescribed a daily 500‑kcal energy deficit and a minimum of 150 minutes of physical activity each week. Demographics, comorbidities, dietary adherence, and laboratory values were collected. Protein intake was quantified from a 7‑day weighed food diary collected at baseline and at 4 weeks, reviewed by a registered dietitian using validated nutrient‑analysis software. Accordingly, patients were categorized into HPD group (≥ 1.6 g protein·kg⁻¹·day⁻¹) and SPD group (1.0-1.5 g protein·kg⁻¹·day⁻¹). The primary endpoint was the percentage change in fat‑free mass and fat mass from baseline. Secondary outcomes included changes in body weight and other body‑composition parameters, along with safety assessments.

Results

Twenty‑seven adults completed the 4‑week assessment, among those 18 were on a SPD and 9 on a HPD. Baseline characteristics were comparable, although HPD participants were slightly younger (median 44 years, IQR 43-56 vs 51 years, IQR 45-61) and included more men (3, 33.3% vs 1, 5.6%). After four weeks of tirzepatide 2.5 mg, the BMI reduction was similar in both groups (HPD: 30.0, IQR 29.4-32.8 to 28.6, IQR 27.6-31.7; SPD: 30.9, IQR 29.5-34.6 to 29.7, IQR 27.8-32.8). Median fat mass declined by ‑3.1 kg (‑12.6 % of baseline) in the HPD group, whereas the SPD group lost ‑1.5 kg (‑5.5 %) with p=0.011. Considering fat-free mass, patients receiving SPD experienced a median loss of ‑5.0 kg (‑10.8 %), while those on HPD gained +1.6 kg (+3.2 %) with p=0.011. Total body water increased by 1.3 L in HPD and decreased by 2.0 L in SPD, mirroring the divergent lean‑mass trajectories. Lipid profiles and glycaemic indices showed similar improvements in both cohorts, and no adverse events were reported.

Conclusion

In adults initiating tirzepatide, coupling a high‑protein diet with standard energy restriction preserved—and modestly increased—fat‑free mass, while doubling adipose‑tissue loss relative to a standard‑protein diet, without compromising overall BMI reduction or metabolic safety. These findings support prioritising higher protein targets to optimize body‑composition outcomes during early tirzepatide therapy and warrant confirmation in prospective, controlled trials of longer duration.

Disclosure

None to declare

Clinical Case Summary

Celiac disease (CD), an autoimmune enteropathy triggered by gluten ingestion, commonly presents with gastrointestinal symptoms but can also manifest with various extra-intestinal symptoms, including cutaneous manifestations. Erythema nodosum (EN), a form of acute hypodermitis, is a rare extra-intestinal manifestation of CD and is often associated with other conditions such as infections and inflammatory enteropathies. We report the case of an 11-year-old girl who presented with erythema nodosum and was subsequently diagnosed with celiac disease. The patient exhibited deep, painful red nodules on the anterior surface of both legs and the dorsal surface of the feet, which persisted for a month prior to her referral. Laboratory testing revealed markers of celiac disease, and endoscopic evaluation revealed mosaic antritis and duodenitis with a characteristic fish-scale appearance. Duodenal biopsy confirmed a diagnosis of celiac disease (Marsh stage 3c class), with a significant intraepithelial lymphocytosis of 47%. After initiating a strict gluten-free diet, the patient showed complete resolution of the skin lesions within six weeks. This case underscores the importance of considering celiac disease in the differential diagnosis of erythema nodosum, particularly in patients with unexplained cutaneous manifestations. It also highlights the potential benefits of early screening for celiac disease in patients with EN, as a strict gluten-free diet can lead to both dermatological and gastrointestinal improvement. Further research is needed to establish a clear causal relationship between celiac disease and erythema nodosum.

Clinical Case Summary

Melioidosis, caused by Burkholderia pseudomallei, is an infectious disease endemic to tropical and subtropical regions. It poses a particular risk to immunocompromised individuals. This case report describes a 48-year-old male with Crohn's disease on biologic therapy who developed pulmonary melioidosis—a condition rarely reported among patients receiving biologics for inflammatory bowel disease.
A 48-year-old male, working as a plaster renderer in rural Queensland, presented with a productive cough, sore throat, fever, and night sweats. He had a background of Crohn’s disease and ankylosing spondylitis, managed with Adalimumab, mesalazine, and intermittent corticosteroids. He denied recent travel or gardening exposure.
Melioidosis was confirmed by positive cultures for Burkholderia pseudomallei from sputum and bronchial washings. Imaging demonstrated bilateral lower zone airspace opacities, a right-sided pleural effusion, and mediastinal lymphadenopathy, with CT features suggestive of a mass-like lesion in the right middle lobe bronchus. The overall picture was consistent with pulmonary melioidosis complicated by lymphadenopathy.
The patient received intravenous ceftazidime for four weeks, followed by oral trimethoprim-sulfamethoxazole for three months. Adalimumab was withheld during the acute infection, and he was managed with mesalazine (4.8 g daily) and prednisolone (20 mg daily) for his IBD.
Conclusion: In melioidosis-endemic areas, inflammatory bowel disease patients receiving biologic therapy can be safely managed if there is early recognition and prompt initiation of appropriate antimicrobial treatment. This case underscores the importance of maintaining a high index of suspicion for melioidosis in immunosuppressed patients presenting with respiratory symptoms in endemic regions.

References

1. Image of CT cross sectional image of right middle lobe mass

Clinical Case Summary

Introduction: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder with multisystem involvement, predominantly affecting the cardiovascular system. Aortic aneurysms and dissections are common complications. LDS shares features with other connective tissue disorders, such as Marfan and Ehlers-Danlos syndromes (1).
Case report: A 44-year-old male with a marfanoid habitus, history of thyroid carcinoma treated with radioactive iodine, appendectomy complicated by hematoma and dehiscence, and Loeys-Dietz syndrome type 3 (SMAD3 variant), diagnosed after a Stanford type A aortic dissection in 2022. In 2023, he underwent left carotid-subclavian bypass and ascending aortic aneurysm repair with hybrid graft. Family history included aortic dissection and hiatal hernia. He was on levothyroxine, dicoumarol, and omeprazole. Referred to the motility unit for preoperative evaluation of a large hiatal hernia seen on CT (Figure 1A).
He reported diet-related occasional nocturnal heartburn and regurgitation, well-controlled with PPIs. No dysphagia or alarm symptoms. Gastroscopy showed an 8–10 cm partially volvulated hernia sac without mechanical or vascular compromise. Esophagogram (1B) confirmed a mixed hiatal hernia with severe reflux and delayed esophageal clearance. High-resolution manometry with impedance (HRIM) showed a short esophagus (21 cm), ineffective motility, incomplete bolus transit and early post-swallow reflux (1C). Due to high risk of postoperative dysphagia, partial fundoplication was advised, but conservative management was chosen given prior surgical dehiscence and good symptom control.
Discussion: Gastrointestinal manifestations of LDS are rare and understudied. Large hiatal and abdominal wall hernias are among the most frequent findings, due to altered structural support at the esophagogastric junction (4,5). GERD symptoms are common and may require multidisciplinary care. HRIM is essential for preoperative planning in these patients.

References

1. Gouda, P., Kay, R., Habib, M., Aziz, A., Aziza, E., & Welsh, R. (2022). Clinical features and complications of Loeys-Dietz syndrome: A systematic review. International journal of cardiology, 362, 158–167. https://doi.org/10.1016/j.ijcard.2022.05.065
2. Wang, X. J., Babameto, M., Babovic-Vuksanovic, D., Bowen, J. M., & Camilleri, M. (2021). Audit of Gastrointestinal Manifestations in Patients with Loeys-Dietz Syndrome and Vascular Ehlers-Danlos Syndrome. Digestive diseases and sciences, 66(4), 1142–1152. https://doi.org/10.1007/s10620-020-06265-8
3. Honrubia Lopez, R., Burgos García, A., & Palacios Lázaro, E. (2017). Multiple perforation of small-intestine diverticula in a patient with Ehlers-Danlos syndrome. Revista espanola de enfermedades digestivas, 109(1), 83. https://doi.org/10.17235/reed.2016.4452/2016
4. Castori, M., Morlino, S., Pascolini, G., Blundo, C., & Grammatico, P. (2015). Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. American journal of medical genetics. Part C, Seminars in medical genetics, 169C(1), 54–75. https://doi.org/10.1002/ajmg.c.31431
5. Thwaites, P. A., Gibson, P. R., & Burgell, R. E. (2022). Hypermobile Ehlers-Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know. Journal of gastroenterology and hepatology, 37(9), 1693–1709. https://doi.org/10.1111/jgh.15927

Clinical Case Summary

An 82-year-old man with Child B alcoholic cirrhosis, complicated by portal hypertension, underwent surveillance upper digestive endoscopy (UDE), revealing large esophageal varices and a 20 mm exophytic lesion, 40 cm from the dental arch, with an infiltrative and ulcerated appearance. Biopsies were inconclusive. Endoscopic ultrasound identified a heterogeneous, amorphous lesion with poorly defined borders and disruption of all wall layers, complicated by numerous large varices, preventing biopsy due to hemorrhagic risk. Computed tomography revealed parietal thickening in the distal esophagus and multiple varices, complicating lesion delineation. An oncology consultation recommended clinical surveillance, considering the patient's age, comorbidities, indeterminate nature of the esophageal lesion, and low suspicion for adenocarcinoma on ultrasound. One year later, surveillance UDE showed regression of the lesion.Histological samples were reviewed, revealing changes consistent with pyogenic granuloma. Pyogenic granuloma is a rapidly growing capillary hemangioma that may occur within the lumen of a pre-existing vessel (intravascular variant). The case is supported by appropriate iconography.

This case is presented with imaging, highlighting the challenge due to the macroscopic appearance suggestive of a neoplastic lesion and the pyogenic granuloma's growth within esophageal varices, limiting diagnostic and therapeutic management.

References

Introduction

Inflammatory Bowel Disease (IBD) patients carry a high risk of malnutrition, independently of disease activity. Screening for malnutrition in IBD is currently recommended since malnutrition, as well as low Fat-Free Mass Index (FFMI), have been associated to poor disease outcomes. However, due to a non-universal definition of malnutrition, most Nutritional Screening Tools (NSTs) have been validated compared to different reference methods and do not consider patients’ body composition. Moreover, the ability of most NSTs to predict malnutrition over time has not been explored.

Aims & Methods

The aim of this study was to compare the efficacy of different NSTs to predict malnutrition, as defined by the ESPEN 2015 and GLIM criteria, and a low FFMI in a cohort of inactive/mildly active IBD patients.
This is a prospective, single center, cohort study enrolling Crohn’s disease (CD) and ulcerative colitis (UC) patients in clinical remission or with mildly active disease as defined by Harvey-Bradshaw Index and partial Mayo Score, respectively. MUST, MIRT, MNA, NRS-2002 and SaskIBD-NR questionnaires and Bioelectrical Impedance Analysis (BIA) were performed at baseline and after six months follow-up. A low FFMI was defined as <18 kg/m2 in males and <15 kg/m2 in females. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the accuracy of the different NSTs for the detection of malnutrition and low FFMI at six months were calculated.

Results

Sixty-six (CD: 32; UC: 34) IBD patients were enrolled. Median age was 55.5 years (IQR 34-62.8), median disease duration was 10 years (IQR 6-17). At baseline, all CD and 30/34 (88%) UC patients were in clinical remission; median C-reactive protein was 0.8 mg/L (IQR 0-3.8), median fecal calprotectin was 55.2 mcg/g (IQR 12.9-326). Of the entire cohort, 6/66 (9%) and 17/66 (26%) patients were malnourished according to GLIM and ESPEN criteria, respectively, [(GLIM CD:3, UC: 3)(ESPEN: CD: 3; UC:14)] and 5/66 (8%) had low FFMI (CD:1; UC: 4). At 6 months follow-up, all CD and 31/34 (91%) UC patients were in clinical remission. Ten out of 66 (15%) and 32/66 (48%) patients were malnourished according to GLIM and ESPEN criteria, respectively [(GLIM CD:5, UC: 5)(ESPEN: CD: 15; UC:17)], 11/66 (17%) patients had low FFMI (CD: 3; UC: 8). Baseline MIRT showed the highest sensitivity for the diagnosis of both ESPEN and GLIM-defined malnutrition at 6 months (ESPEN: 40.5%; GLIM: 50%). For ESPEN, MIRT and NRS2002 were the most accurate NSTs (MIRT: 50%, NRS2002: 51.5%), while SaskIBD (75.8%) showed the highest accuracy in detecting GLIM-malnourished patients at 6 months follow up. Among all NSTs, baseline MIRT, MNA and NRS2002 had the highest sensitivity for the detection of low FFMI at six months (MIRT, MNA, NRS2002: 45.5%), while SaskIBD_NR was the most accurate (80.3%).

Conclusion

MIRT might be the NSTs of choice to predict defined malnutrition and low Fat-Free Mass Index at 6 months follow-up in a cohort of inactive/mildly active IBD patients.

References

Huang S, Niu Y, Liu X, Gu Z, Huang A, Wu J. Characteristics of malnutrition according to Global Leadership Initiative on Malnutrition criteria in non-surgical patients with inflammatory bowel disease. Nutrition. 2022;94:111514. doi:10.1016/j.nut.2021.111514

Jensen GL, Cederholm T, Correia MITD, et al. GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community. JPEN J Parenter Enteral Nutr. 2019;43(1):32-40. doi:10.1002/jpen.1440

Cederholm T, Bosaeus I, Barazzoni R, et al. Diagnostic criteria for malnutrition - An ESPEN Consensus Statement. Clin Nutr. 2015;34(3):335-340. doi:10.1016/j.clnu.2015.03.001

van Bokhorst-de van der Schueren MA, Guaitoli PR, Jansma EP, de Vet HC. Nutrition screening tools: does one size fit all? A systematic review of screening tools for the hospital setting. Clin Nutr. 2014;33(1):39-58. doi:10.1016/j.clnu.2013.04.008

Ding NS, Tassone D, Al Bakir I, et al. Systematic Review: The Impact and Importance of Body Composition in Inflammatory Bowel Disease. J Crohns Colitis. 2022;16(9):1475-1492. doi:10.1093/ecco-jcc/jjac041

Introduction

Pancreatic exocrine insufficiency (PEI) is a condition characterized by inadequate secretion or activity of pancreatic enzymes, resulting in the maldigestion and malabsorption of nutrients. While PEI is most commonly associated with chronic pancreatitis and cystic fibrosis, it also occurs frequently in the context of pancreatic and peri-pancreatic malignancies. In patients with pancreatic cancer PEI arises due to direct tumor infiltration, ductal obstruction, parenchymal destruction, or as a consequence of surgical resection. Other gastrointestinal malignancies, such as ampullary or biliary tree cancers, may also contribute to PEI through similar mechanisms. Importantly, PEI in cancer patients is often under-recognized, despite its significant impact on nutritional status, quality of life, and overall prognosis. Timely identification and management of PEI in malignancy-associated cases is crucial to optimize clinical outcomes and support ongoing cancer therapies.

Aims & Methods

The objective of this study is to assess the incidence of PEI in patients with biliopancreatic and ampullary tumors, to explore potential differences in PEI occurrence based on tumor location and to investigate possible associations between PEI and relevant biomarkers.
We conducted a retrospective observational analysis of a consecutively recruited patient cohort including patients diagnosed with biliopancreatic and ampullary tumors at a tertiary care hospital between 2016 and 2024.
PEI was defined as fecal elastase-1 (FE-1) levels below 100 µg/g.
At the time of diagnosis, we collected data on demographic characteristics, tumor-related variables, the incidence of PEI, and serum nutritional markers.

Results

We included 408 patients with malignancies potentially associated with PEI. Of these, 54.2% were male, with a mean age of 72 years (range: 38–101) and a mean body mass index (BMI) of 25.45 (SD ± 4.28).
The types of malignancies included were pancreatic ductal adenocarcinoma (PDAC) in 63.5% of patients, cholangiocarcinoma (CCA) in 23.8%, ampullary tumors in 9.8%, and gallbladder tumors in 2.9%. The overall incidence of PEI at the time of diagnosis was 38.2%. Among subgroups, the incidence was 51.4% in PDAC patients, 13.4% in those with CCA, and 25% in those with ampullary tumors. PEI incidence was significantly associated with elevated HbA1c (>5.8%, p<0.01) and Ca 19-9 levels (>37 U/mL, p<0.01).
In PDAC, tumors located in the pancreatic head were associated with a significantly higher incidence of PEI (58.8%) compared to tumors in the body (27.8%) and tail (21.7%) (p<0.01). In this subgroup, PEI was significantly associated with elevated HbA1c (>5.8%, p=0.03), elevated Ca 19-9 (>37 U/mL, p=0.04), and elevated bilirubin (>1.2 mg/dL, p<0.01).
In contrast, among CCA patients, no significant differences in PEI incidence were observed based on tumor location, and no significant associations were found between PEI and the clinical or laboratory variables analyzed .

Conclusion

• PEI is observed not only in patients with PDAC but also in those with CCA and ampullary tumors at the time of diagnosis.
• Given the high incidence of PEI in tumors located in the pancreatic head, empirical pancreatic enzyme replacement therapy should be considered in this subgroup.
• In PDAC patients, the presence of PEI is significantly associated with endocrine dysfunction, hyperbilirubinemia secondary to biliary obstruction and elevated Ca 19-9 levels.