Search Results (36)

Introduction: Benralizumab has demonstrated rapid efficacy in treating severe eosinophilic asthma (SEA). This study aims to characterize early responses to benralizumab, the patient features observed in those with early responses, and the potential patient features that could predict them, and it also evaluates whether these improvements are sustained during a one-year follow-up (FUP) in clinical practice. Methods: This analysis was conducted using the ORBE II study database. ORBE II is an observational, retrospective study that included uncontrolled SEA adult patients treated with benralizumab according to routine clinical practice in Spain. We analysed patients with available data on the asthma control test (ACT) at baseline and within the first 120 days after benralizumab initiation, identifying ACT “Early Super-Responders” (ACT-ESR) as patients with a ≥9 point-improvement in the ACT score or reaching an absolute score of ≥24. Likewise, we assessed patients with available data on the pre-BD FEV₁ during the same study periods, defining those with a pre-BD FEV₁ increment of ≥230 mL as FEV₁-ESR patients. Clinical outcomes were described up to 1 year of FUP. Results: A total of 45 and 65 patients with data for ACT and FEV₁, respectively, during the first 120 days of treatment were analysed. Of those, 55.5% and 58.5% of patients were categorized as ACT-ESR and FEV₁-ESR, respectively. At baseline, both groups showed high T2 inflammation markers and a high prevalence of comorbidities (chronic rhinosinusitis with nasal polyposis: 56% and 50%; gastro-oesophageal reflux disease: 24% and 40%, respectively). Poor asthma control (ACT < 20) was observed at baseline in 96% of ACT-ESR, while impaired lung function (pre-BD FEV₁ < 80%) was present in 71.7% of FEV₁-ESR. Oral corticosteroid (OCS) dependency affected 25% and 30% of ACT-ESR and FEV₁-ESR, respectively. The early gains observed in ACT-ESR and FEV₁-ESR were sustained up to 1 year of FUP, with 90.5% and 66.7% of patients achieving a super-response (zero exacerbations and no OCS use) and 92.0% and 71.1% meeting clinical remission criteria (zero exacerbations, no OCS use, ACT ≥ 20 and pre-BD FEV₁ increment of ≥100 mL), respectively. Conclusions: Benralizumab provides early benefits for SEA patients in clinical practice, with more than half achieving early super-responses in both ACT score and lung function. These improvements were sustained over a 1-year FUP, resulting in high rates of clinical remission. Full article

Background: Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) is a standard of care for patients with locally advanced gastro-oesophageal adenocarcinoma (GEA) in Western guidelines, but its use is limited in Asian patients. We report outcomes from a single Asian centre of perioperative FLOT with concomitant granulocyte colony-stimulating factor (GCSF) prophylaxis. Methods: A retrospective analysis of all 56 stage II to III GEA patients treated with perioperative FLOT at the National Cancer Centre Singapore between June 2017 and February 2024 was performed. All patients were discussed at a multidisciplinary tumour board, underwent preoperative laparoscopic staging, and received prophylactic GCSF with perioperative FLOT. Surgery was performed across four partner institutions. The primary endpoints were the tolerability of FLOT and pathological complete response (pCR). A univariate analysis of factors associated with survival and adverse events was also performed. Results: Overall, 33 patients (58.9%) completed eight cycles of pre- and postoperative FLOT, and 92.9% underwent resection. The commonest grade 3 to 4 adverse events (AEs) were diarrhoea (10.7%) and neutropenia (5.6%). The 30- and 90-day postoperative mortality rates were 0% and 1.9%, respectively. In resected tumours, the pCR was 15.4%. The median DFS was 27.5 months, but the median OS was not reached. The values for 1-, 2-, and 3-year DFS were 74.6%, 61.0%, and 46.5%, respectively. The values for 1-, 2-, and 3-year OS were 85.0%, 67.4%, and 61.0%, respectively. In the univariate analysis of patients who underwent resection, an ECOG status of 0 was associated with better DFS, while ypN0, R0 resection, and pathological stages 0-II were associated with better DFS and OS. Patients ≥ 65 years benefited from FLOT similarly to those <65 years in terms of DFS (HR 1.03; p = 0.940) and OS (HR 1.08; p = 0.869), with similar rates of grade 3 to 4 AEs. Patients with a higher housing index (HI) were less likely to experience ≥grade 3 AEs compared to those with a lower HI (OR 0.16, p = 0.029). Conclusions: This study presents a unique real-world Asian experience of perioperative FLOT with prophylactic GCSF use, with low rates of G3 to 4 neutropenia. The tolerability of FLOT was similar to that reported in Western populations. Furthermore, similar survival and rates of grade 3 to 4 AEs were observed in elderly patients. Patients of lower socioeconomic status were more likely to experience severe AEs, highlighting the need to proactively support vulnerable groups during treatment. Full article

The aim of this in vivo study was to compare total protein present in the salivary films (F) and acquired enamel pellicle (AEP) on eroded and non-eroded surfaces in patients suffering from GORD symptoms with and without GORD diagnosis (GORD, No-GORD). Thirty-nine patients suffering from GORD symptoms and erosive tooth wear on lower first molars and an unaffected posterior occlusal surface in the same quadrant were recruited from Guy’s hospital, London. Salivary film and AEP were collected from the eroded and uneroded occlusal surfaces, using 0.5% sodium dodecyl sulphate (SDS)-soaked filter papers. Total protein concentration was analysed using bicinchoninic acid assay (BCA). Statistical analysis was conducted using Shapiro–Wilk, ANOVA, and Tukey’s tests (p < 0.05), comparing four GDS sample types and GORD vs. No-GORD groups. The level of significance was set as p < 0.05. Data were compared between eroded and uneroded surfaces in the same patient with GORD symptoms, as well as between those with or without a GORD diagnosis (GORD, No-GORD). The AEP total protein concentration from the eroded [2.17 (0.49) mg/mL] and uneroded surfaces [2.24 (0.66) mg/mL] of the GORD group were statistically significantly lower than those on eroded [3.27 (1.01) mg/mL] and uneroded [3.33 (1.57) mg/mL] surfaces in the No-GORD group (p = 0.007) (p = 0.008), respectively. No statistically significant differences were observed for film and AEP between eroded and uneroded surfaces (p > 0.05). Full article

Khat leaves, indigenous to eastern Africa, have been chewed for centuries for their stimulant effects, attributed to alkaloids such as cathinone and cathine. Although associated with gastric disorders like gastritis and gastro-oesophageal reflux disease, the underlying molecular mechanisms remain unclear. This study aimed to examine the morpho-anatomy of khat leaves using light microscopy and histochemistry and to assess the effects of leaf extracts and alkaloids on human gastric epithelial cells (GES-1). The study identified specific cells in the palisade–spongy transition zone as storage sites for psychoactive alkaloids. Leaf extracts were prepared by mimicking the chewing process, including a prolonged salivary phase followed by a gastric phase. Cytotoxicity and cell viability were evaluated using LDH and MTT assays, respectively. Additionally, the impact on IL-8 secretion, a key chemokine in gastric inflammation, was analysed under normal and TNF-α-stimulated conditions. The results showed no increase in cytotoxicity up to 250 µg/mL. However, there was a significant decrease in cell metabolism and a reduction in both basal and TNF-α-induced IL-8 secretion, but cathinone and cathine were inactive. These findings suggest that khat may not directly cause the gastric issues reported in the literature, which would rather be attributed to other confounding factors, highlighting the need for further research to clarify its biological impacts. Full article

A growing body of evidence suggests that the effects of poor oral hygiene extend beyond the oral cavity and are associated with a variety of systemic diseases, including asthma. Asthma, which results in symptoms of cough, wheezing, and dyspnoea, and is characterized by airflow limitation with variability and (partial or complete) reversibility, is amongst the most prevalent respiratory diseases with approximately 262 million patients worldwide, and its prevalence and disease burden is on the increase. While asthma can occur at a young age, it can also develop later in life and affects a variety of age groups. Both of these diseases have a chronic course, and various researchers have suggested a link between the two. In this article, we aim to provide a literature review focusing on the association between the two diseases. The results demonstrate that medications (primarily, inhaler medicine), hypoxia induced by asthma, and the breathing behaviour of patients potentially trigger periodontal disease. In contrast, oral periodontopathogenic microorganisms and the inflammatory mediators produced by them may be involved in the onset and/or exacerbation of asthma. Common contributing factors, such as smoking, gastro-oesophageal reflux, and type-2 inflammation, should also be considered when evaluating the relationship between the two diseases. Full article

Barrett’s oesophagus is a pathological condition whereby the normal oesophageal squamous mucosa is replaced by specialised, intestinal-type metaplasia, which is strongly linked to chronic gastro-oesophageal reflux. A correct endoscopic and histological diagnosis is pivotal in the management of Barrett’s oesophagus to identify patients who are at high risk of progression to neoplasia. The presence and grade of dysplasia and the characteristics of visible lesions within the mucosa of Barrett’s oesophagus are both important to guide the most appropriate endoscopic therapy. In this review, we provide an overview on the management of Barrett’s oesophagus, with a particular focus on recent advances in the diagnosis and recommendations for endoscopic therapy to reduce the risk of developing oesophageal adenocarcinoma. Full article

Historically, oesophageal and gastro-oesophageal junction adenocarcinomas were associated with a poor prognosis. The advent of neoadjuvant therapy has transformed the management of oesophageal and gastro-oesophageal junction adenocarcinomas further and offers the possibility to reverse disease progression, eliminate micrometastasis, and offer potentially better outcomes for these patients. This review provides an overview of landmark clinical trials in this area, with different treatment regimens considered over the years as well as potential therapeutic agents on the horizon that may transform the management of oesophageal and gastro-oesophageal junction adenocarcinomas further. Full article

Gastric cancer (GC) is an important cause of cancer worldwide with over one million new cases yearly. The vast majority of cases present in stage IV disease, and it still bears a poor prognosis. However, since 2010, progress has been made with the introduction of targeted therapies against HER2 and with checkpoint inhibitors (PDL1). More agents interfering with other targets (FGFR2B, CLDN18.2) are being investigated. cMET is a less frequent molecular target that has been studied for gastric cancer. It is a proto-oncogene that leads to activation of the MAPK pathway and the PI3K pathway, which is responsible for activating the MTOR pathway. The prevalence of cMET is strongly debated as different techniques are being used to detect MET-driven tumors. Because of the difference in diagnostic assays, selecting patients who benefit from cMET inhibitors is difficult. In this review, we discuss the pathway of cMET, its clinical significance and the different diagnostic assays that are currently used, such as immunohistochemy (IHC), fluorescence in situ hybridization (FISH), the H-score and next-generation sequencing (NGS). Next, we discuss all the current data on cMET inhibitors in gastric cancer. Since the data on cMET inhibitors are very heterogenous, it is difficult to provide a general consensus on the outcome, as inclusion criteria differ between trials. Diagnosing cMET-driven gastric tumors is difficult, and potentially the only accurate determination of cMET overexpression/amplification may be next-generation sequencing (NGS). Full article

In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients. Full article

Gastroesophageal reflux disease (GORD) affects up to 20% of Western populations, yet sensory mechanisms underlying heartburn pathogenesis remain incompletely understood. While central mechanisms of heartburn perception have been established in earlier studies, recent studies have highlighted an important role of neurochemical, inflammatory, and cellular changes occurring in the oesophageal mucosa itself. The localization and neurochemical characterisation of sensory afferent nerve endings differ among GORD phenotypes, and could explain symptom heterogeneity among patients who are exposed to similar levels of reflux. Acid-induced stimulation of nociceptors on pain-sensing nerve endings can regulate afferent signal transmission. This review considers the role of peripheral mechanisms of sensitization in the amplification of oesophageal sensitivity in patients with GORD. Full article

Introduction: Potassium Permanganate (KMnO₄) is an uncommon cause of caustic ingestion in teenagers and adults; only case reports are found in the recent literature. At Ngwelezana Hospital in South Africa, KMnO₄ ingestion is not an uncommon indication for admission. KMnO₄ is readily available as used in most households and recommended for medicinal purposes by traditional health practitioners. Aim: To ascertain the reasons for KMnO₄ ingestion, the extent and severity of injury as determined by upper gastro-intestinal studies, and patient outcomes in comparison with the available global literature. Methods: We performed a retrospective study of 26 teenage and adult patients, admitted to our adult wards following KMnO₄ ingestion. Data collected on patient demographics, reason for KMnO₄ ingestion, and quantity ingested. Oral inspection and upper gastro-intestinal study findings recorded with grading (Zargar) of corrosive injury to oesophagus and stomach. Patients’ outcome and duration of hospital stay documented. Results: There were 73% females and 27% males, with an average age of 23 years. Reasons for ingestion included parasuicide (84%), accidental ingestion (8%), and for relief of abdominal pain (8%). The vast majority (96%) swallowed KMnO₄ in solution rather than in solid form. The volume and concentration of KMnO₄ taken was difficult to quantify. Oral discoloration, oedema, and ulceration were found in 58%. Gastro-intestinal endoscopy was performed in 92%; abnormalities were demonstrated in 68% (oesophageal injury 14%, oesophageal and gastric injuries 14%, gastric injury alone 41%). Oesophageal injuries: n = 6; Zargar grade 1—83%, Zargar grade 2A—17%. Gastric injuries: n = 12; Zargar grade 1—42%, Zargar grade 2A—33%, Zargar grade 2B—25%. Average hospital stay was 2.9 days (range 2–8 days). There were no mortalities and no complications at 6 weeks. Conclusion: KMnO₄ ingestion by teenagers and adults is not uncommon in our setting, mostly related to suicide attempts and most often taken in liquid form. KMnO₄ was possibly of a low concentration as no systemic complications were noted and there were milder gastric and oesophageal injuries as compared to case reports from elsewhere of mucosal necrosis following ingestion of KMnO_4. Full article

Background/Aim: The aim of this study was to compare high-resolution manometry (HRM) and upper gastrointestinal (GI) endoscopy as diagnostic utilities in detecting a sliding hiatus hernia in patients with gastro-oesophageal reflux disease (GORD) symptoms. Material and Methods: For both diagnostic modalities, the data obtained from 31 patients (20 females; mean age 48.2) who qualified for Nissen fundoplication were analysed using oesophageal pressure topography in line with the Chicago Classification. Confirmation of hiatus hernia during the surgery was considered the gold standard. HRM protocol involved 10 consecutive boluses of 10 mL of water. Results: Sliding hiatus hernia was confirmed intraoperatively in 29 out of 31 patients. In 14 patients, hiatus hernia was detected in HRM, while 19 patients were found to have hiatus hernia by upper GI endoscopy before surgery. No false positive results were obtained in HRM, while 15 false negative results were shown. In upper GI endoscopy, false positive data were observed in 1 patient, while false negative results were found in 10 patients. Thus, the sensitivity of HRM in detecting hiatus hernia was 48% (95%CIs: 29–67%), and sensitivity of upper GI endoscopy was 66% (95%CIs: 46–82%). It was not possible to assess the specificity of HRM or upper GI endoscopy because only 2 of 31 patients had no hiatus hernia during fundoplication (gold standard). False negative results (sensitivity) were not significantly different between compared diagnostic modalities HRM and upper GI endoscopy (52% vs. 34%, respectively, p = 0.29). Conclusions: Due to poor sensitivity, both modalities, i.e., HRM and upper GI endoscopy, are not reliable tools to diagnose sliding hiatus hernia in patients with GORD symptoms. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ∼3 years. Several risk factors have been identified, such as age, genetic predisposition, tobacco exposure, and gastro-oesophageal reflux disease (GERD). Prevalence of GERD in IPF is high and may affect 87% of patients, of whom only half (47%) report symptoms. Objective: The aim of this study is to review current evidence regarding the correlation between GERD and IPF and to evaluate the current studies regarding treatments for GERD-IPF. Methods: A review to identify research papers documenting an association between GERD and IPF was performed. Results: We identified several studies that have confirmed the association between GERD and IPF, with an increased acid exposure, risk of gastric aspiration and bile acids levels in these patients. Few studies focused their attention on GERD treatment, showing how antiacid therapy was not able to change IPF evolution. Conclusions: This review investigating the correlation between GERD and IPF has confirmed the hypothesized association. However, further large prospective studies are needed to corroborate and elucidate these findings with a focus on preventative and treatment strategies. Full article

Introduction: Robotic surgery has shown explicit benefits and advantages in adults, but it is not yet strongly established in the pediatric population, even though its popularity is increasing, especially in the urologic field. Materials and methods: In this article we present our experience with the Da Vinci System (SI first and XI nowadays) at our pediatric institution in order to analyze our progress over the years. We considered all patients from the start of the robotic surgery program in 2016 until the end of 2021, dividing them into general abdominal surgery and genitourinary surgery. Analyzed data were the patient’s demographic, details of surgery, and intra and post-operative complications. Results: The total number of patients (pts) included in this study was 76, of whom 40 (52%) were male and 36 (48%) were female. The mean age at surgery was 90.9 months (range 10–207 months), and the mean weight at surgery was 29.3 kg (range 9.5–68 kg). There were 18 general abdominal robotic surgeries and 58 genitourinary robotic surgeries performed. The most performed surgeries in these two categories were fundoplication for gastro-oesophageal reflux disease (11%) and Anderson–Hynes pyeloureteroplasty. The mean operative time was 224.2 min (range 72–530 min): the mean times in the two groups (general abdominal surgery and genitourinary surgery) were 165 min (range 84–204 min) and 194 min (range 95–360 min), respectively. A total of four (5%) minor complications were reported. The total conversions were two (2.6%) and the mortality rate was 0%. Conclusions: Pediatric robotic surgery is a field of considerable interest and it is rapidly expanding. In our experience, it is evident how the learning curve has increased gradually, but steadily, allowing us to advance from standardized surgery, such as fundoplication and pieloplasty, towards a more technically complex one, achieving the same good results. We believe that robotic surgery is very respectful of tissues and feasible, especially for reconstructive surgery. For these reasons, it could become of common use also in the pediatric population, overcoming impediments such as excessive cost and the lack of pediatric instruments, in order to be able to treat children with a progressively lower age and weight. Full article

Eosinophilic gastroenteritis (EGE) is a subgroup of the eosinophilic gastro-intestinal disorders (EGIDs), characterized by eosinophilic infiltration and chronic inflammation of the gastrointestinal tract. These are rare diseases with still incompletely elucidated causes and mechanisms, with frequently delayed diagnosis and variable outcome. Despite increased interest in eosinophilic diseases in recent years, fewer data have been published on EGE and no standardized diagnostic and therapeutic approach exists. This paper reports the case of a young male patient diagnosed with EGE in 2017 based on clinical and histopathological criteria and constantly monitored during five years. Besides gastrointestinal eosinophilic infiltration, biopsies also revealed eosinophilic infiltration of the oesophagus, despite no declared characteristic oesophageal symptoms. We found increased specific IgE to multiple foods and progressive blood hypereosinophilia which preceded EGE diagnosis by three years. The EGE management included selective dietary restrictions and pharmacologic therapy based on daily budesonide non-enteric coated tablets, proton pumps inhibitors, antihistamines, cromoglycate, correction of iron, calcium and vitamin D deficiencies. The clinical outcome was good, while blood eosinophilia and endoscopic appearance remained almost unchanged. After one year the patient complained of respiratory symptoms suggesting asthma, needing continuous combined inhaled therapy. The reported case is illustrative for complex presentation, diagnosis and outcome of a rare case of mucosal chronic EGE associated with oesophageal involvement, peripheral eosinophilia, multiple food allergies and asthma. Full article