Mater Dei Hospital

Panenteric capsule endoscopy is a novel method of assessing the gastrointestinal (GI) tract from the mouth to the anus. This has been made possible through technological advancements of having two cameras on a capsule with a wide-angle view, an adaptive frame rate, and better battery life. Specific bowel preparation with specific instructions needs to be administered. In this chapter, we review the type of bowel preparation instructions that need to be administered together with the clinical indications, these being mainly inflammatory bowel disease and GI bleeding. The limitations of this test are also reviewed as though the potential for a panenteric assessment is available, and one has to be careful on its use due to the current concerns of esophageal, gastric, and colonic mucosa visualization.

This chapter attempts to give practical answers to frequently asked questions (FAQs) and settings related to video capsule endoscopy. The statements represent a personal view from the authors’ experience. For more details and further references, the reader is referred to the corresponding chapters.

Background Duodenal biopsies are standard for diagnosing celiac disease (CD), but a biopsy-free approach has gained attention in the past decade. Evidence suggests that immunoglobulin A anti-tissue transglutaminase (IgA tTg) antibody levels ≥10 times the upper limit of normal (ULN) may reduce the need for histology. This study aimed to assess whether IgA tTg antibody titers ≥10 × ULN correlate with the histological diagnosis in adults. Methods The retrospective study was conducted at Mater Dei Hospital, Malta, analyzing adult patients who underwent upper gastrointestinal endoscopy with duodenal biopsies between 2012 and 2024. Data on demographics, symptoms, risk factors, serology and histological results were collected. Patients who had positive serology but initial negative biopsies and underwent repeat biopsies were also reviewed. Results Of 114 patients (78.1% female, mean age 41.0 years), 97.4% tested positive for IgA tTg antibodies and 93.8% for endomysial antibodies (EMA). CD was histologically confirmed in 70.2%, with females more frequently diagnosed than males (75.3% vs. 52%, P=0.025). CD-related symptoms were reported by 79.8%, while 20.2% were asymptomatic. Levels of tTg ≥10 × ULN were found in 41.2% patients, and this cutoff had a sensitivity of 58.8%, specificity of 100%, positive predictive value of 100% and negative predictive value of 50.7% for CD (P<0.001). Conclusion This study supports a biopsy-free approach for diagnosing CD when IgA tTg levels are ≥10 x ULN, especially with EMA positivity and typical clinical presentation.

Introduction Achieving a pCR serves as a biomarker indicating enhanced overall survival for breast cancer patients undergoing NST. Vitamin D enhances the antitumor effect of chemotherapeutics as demonstrated in cancer cells and animal models. In this prospective randomized clinical study, we aim to investigate the effect of oral vitamin D supplementation during neoadjuvant systemic therapy (NST) on pathologic complete response (pCR). Methods Between June 2019 and June 2023, an oral form of 50,000 IU vitamin D3 (cholecalciferol) replacement was administered once a week during NST for the study group. Results There were 114 (50.2%) cases in the study group and 113 (49.8%) in the control group (totally 227 cases). Factors that positively influenced pCR were higher clinical T stage, higher AJCC clinical stage, Estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, high Ki‐67 expression (≥ 20%), hormone negative molecular subtypes, and vitamin D intake in univariate analysis. In the multivariate analysis, factors significantly affecting pCR were vitamin D intake (OR: 2.33, 95% CI 1.20–4.53; p = 0.013), hormone receptor negativity (OR: 2.22, 95% CI 1.11–4.43; p = 0.024), and Ki‐67 ≥ 20% (OR: 3.27, 95% CI 1.03–10.34; p = 0.044). Conclusions This is the first and only study to compare the effect of oral vitamin D supplementation on pCR during NST. Vitamin D supplementation during NST has a significant effect on pCR in breast cancer patients. Although this effect is not significant for axillary pCR, there is an almost significant correlation. Trial Registration ClinicalTrials.gov (Identifier: NCT03986268)

A female in her 70s originally presented with a mechanical fall and a consolidation on a chest x-ray, thought to be secondary to aspiration. Failure to response to medical treatment prompted further investigations which revealed a calcific lesion obstructing the left lower lobe bronchus, histologically confirmed as endobronchial amyloidosis. Amyloidosis is a rare condition characterized by insoluble fibril protein deposition in various organs. Pulmonary amyloidosis can be a manifestation of systemic amyloid disease, or otherwise being isolated in nature. Tracheobronchial amyloidosis is a subtype of lung-related amyloidosis, and in fact being mostly not linked to a systemic form of disease. Removal of the lesion with rigid bronchoscopy led to an excellent recovery. Given that the lesion was focal and endobronchial, the most common manifestations would be complications related to collapse of the airway, including symptoms such as dyspnea or chronic cough and also episodes of recurrent pneumonias. Bronchoscopy and resection of the lesion is the main management of localised endobronchial amyloidosis unless systemic involvement or other complications are present.

Purpose Cycles of in vitro maturation (IVM) of oocytes show asynchrony between embryo development and endometrial receptivity. Hence, elective embryo vitrification/warming (V/W) for embryo transfer (FET) is routinely performed. However, clinical outcomes after IVM are lower compared to conventional ovarian stimulation, mainly due to lower embryo quality. Vitrification at cleavage stage, rather than blastocyst stage, is used to optimize embryo utilization while maintaining acceptable pregnancy rates. The aim of this study is to ascertain the vulnerability to V/W of IVM-derived cleavage-stage embryos and to identify characteristics that predict pregnancy. Methods In this single-center retrospective cohort study, 442 day-3 IVM-derived embryos from PCOS patients were investigated. Cell survival upon warming, cell cycle progression during overnight culture and clinical outcome in 425 FET cycles were analyzed. Results From 442 V/W embryos, 85% were fully intact. Cell loss reduced the cell cycle progression after overnight culture of V/W embryos (p = 0.047) and tended to lower clinical pregnancy rates (16% vs 23%, p = 0.22) compared to intact embryos. Better fresh embryo quality was associated with enhanced cell cycle resumption after overnight culture (p < 0.0001). Cell cycle resumption was required for pregnancy to occur. Additionally, the extent of cell cycle progression (OR = 0.439, CI = 0.24–0.78, p < 0.001) and the number of available top-quality embryos (OR = 0.174, CI = 0.04–0.32, p = 0.01) were indicative for success. Conclusions A clinical pregnancy rate of 23% per FET with V/W IVM-derived cleavage-stage embryo was obtained with cell cycle resumption after overnight culture as dominant predictive factor.

Background The last 15 years have seen new extended half‐life (EHL) recombinant FVIII/IX concentrates and nonreplacement therapy for haemophilia A (emicizumab) introduced in Europe. These changes affect FVIII/IX exposure in previously untreated patients (PUPs) and previously treated patients (PTPs) with severe haemophilia A and B (SHA and SHB) and may modify inhibitor development and/or detection. Aim To report trends in treatment for severe haemophilia and concomitant changes in inhibitor incidence. Methods Between 2008 and 2022, 97 centres reported inhibitor development against FVIII/IX concentrates to the European Haemophilia Safety Surveillance System (EUHASS). Inhibitors were reported quarterly, and PUPs without inhibitor development annually. Cumulative inhibitor incidences (95% confidence intervals [CI]) were calculated for PUPs and incidence rates/1000 years (CI) for PTPs. Results By 2022, SHA‐PUPs ( n = 1574) received emicizumab (44%), SHL‐rFVIII (21.5%), pdFVIII (17.5%) and EHL‐rFVIII (17%). SHB‐PUPs ( n = 236) received EHL‐rFIX (79%) and SHL‐rFIX (21%). SHA‐PTPs (68,772 years) received EHL‐rFVIII (31%), SHL‐rFVIII (28%), emicizumab (25%), and pdFVIII (15%). SHB PTPs (11,185 years) received EHL‐rFIX (69%), pdFIX (15%) and SHL‐rFIX (15%). Observed Inhibitor incidence in SHA‐PUPs decreased from 24% before 2016 to 6% in 2022 ( p < 0.001), and potentially in SHB‐PUPs too (from 9% to 3%; p = 0.066), but remained stable in SHA/SHB PTPs. Conclusion In 2022, 44% of SHA‐PUPs and 25% of SHA‐PTPs received emicizumab prophylaxis. Concomitantly, observed inhibitor incidence reduced to 6% in SHA‐PUPs. In SHB, EHL‐rFIX treatment increased to 79% in SHB‐PUPs and 69% in SHB‐PTPs. Assessing inhibitor incidence for new concentrates is likely to be hampered by novel treatments causing delayed exposure to FVIII/FIX.

Background Pierre Robin Sequence (PRS) is a congenital condition characterized by a triad of micrognathia, glossoptosis, and cleft palate. This study aims to investigate the incidence and epidemiology of PRS in the Maltese population, providing valuable insights into its prevalence, clinical characteristics, and surgical management. Method A population-based retrospective analysis was conducted utilizing data from the years 2000 to 2019. Aggregate data were collected from the Maltese Public Health Department, capturing registered PRS cases in the Maltese population. Incidence rates were calculated, and demographic factors, gestational distribution, and associations with cleft palate were evaluated. Results The incidence of PRS in the Maltese population was found to be 12.5 per 100,000 births, higher than global estimates. Among the registered cases, 63.6% were male. Gestational distribution analysis revealed a concentration of PRS cases born at 39 weeks. Furthermore, 90.9% of PRS cases were associated with cleft palate. Conclusion This study highlights a higher prevalence of PRS in the Maltese population compared with global estimates, indicating a unique epidemiological profile specific to the Maltese Islands. The findings provide valuable insights for plastic surgeons and health care professionals involved in the management of PRS patients. Further research is needed to explore the underlying factors contributing to this increased prevalence and to optimize treatment strategies for PRS patients in the Maltese Islands.

Background & Aims: The presence of backwash ileitis, post-colectomy pre-pouch ileitis, or pouchitis has been widely described in the presentation of ulcerative colitis [UC]. However, over the years, a few cases of upper gastrointestinal [UGI] inflammation in patients with UC have been reported, most commonly post-colectomy. The aim of this review was to conduct an analysis of the current literature to identify the prevalence, risk factors and current treatment of UGI UC. Methods Case report and review of the literature. An electronic search of five bibliographic databases [Pubmed, Cochrane, DOAJ, Science Direct, and JSTOR], was conducted. A combination of keywords and medical subject headings [MeSH] related to “small intestine” and “inflammation” or “enteritis” and “colectomy” or “post operative complications” or “ileostomy” or “stoma” and “ulcerative colitis” or “inflammatory bowel disease” were used. Referenced papers not fully available in English text were excluded from the study. The manuscripts were analysed for age, gender, extent of colonic and UGI disease, timing of UGI presentation, surgical history, treatment and follow-up. Results We present the case of a 59-year-old woman with diffuse upper gastrointestinal (UGI) ulcerative colitis (UC) that was refractory to steroid treatment, occurring nine years after a panproctocolectomy for medical treatment failure Upon initiation of an anti-TNFɑ [adalimumab], she achieved remission. We then systematically reviewed the literature to analyse previous reports of patients presenting with UGI UC to understand the prevalence and identify risk factors for developing this condition. To date, 43 cases have been published describing UGI UC with a male to female ratio 5:4 with a mean age of 37.52 years [IQ range 27 years] The majority [85.7%] of these patients were post-colectomy secondary to pancolitis. The mean time post-colectomy for UGI UC to occur is 14 months [range 0-12 years]. The prognosis of these patients were generally good; however, severe complications including haemorrhage, perforation and death have been reported. The inflammatory distribution affected the duodenum [74%] > ileum [57%] > jejunum [31%] > stomach [4%]. The majority of patients with reported changes in the stomach had a pangastritis pattern, with only one case describing isolated antral inflammation. No standardised treatment strategy is available, however, intravenous and oral corticosteroids, 5-aminosalicylates, thiopurines, calcineurin-inhibitors, and TNFα-inhibitors, have been found to be effective in treating UGI UC. Only one other case report reported the successful use of adalimumab to attain remission in UGI UC. Conclusion: This review sheds light on a rare presentation of UC. This highlights the need for further research into the pathogenesis of UC and treatment strategies for patients presenting with UGI UC. Our case further strengthens the use of anti-TNFɑ, particularly adalimumab for UGI UC and highlights the need for further research into the pathogenesis of inflammatory bowel disease. No disclosures Conflict of Interest None

Background Patients treated with biologics or Janus kinase (JAK) inhibitors have an increased risk of reactivating latent tuberculosis infection (LTBI). ECCO guidance recommends screening for LTBI by using clinical data, epidemiological factors, chest X-ray (CXR), and either a tuberculin skin test or interferon-gamma release assay (IGRA). The evidence supporting CXR use is categorised at level 5. We aimed to determine the relation between CXR and IGRA test results in adults with inflammatory bowel disease (IBD) before starting immunosuppressive therapy in a low-risk population. Methods This retrospective analysis identified adult patients with IBD on biologics or JAK inhibitors and their epidemiological data, CXR, and IGRA results were evaluated. Results 356 patients diagnosed with IBD were included, 58.7% ( n = 209) being male. Most patients had Crohn’s disease (66.6%, n = 237), 30.6% ( n = 109) had ulcerative colitis, and the remaining 2.8% were classified as IBD-unclassified. The mean age of IBD diagnosis was 30.3 years (SD ± 15.7). None of the patients had any clinical suggestion or exposure to tuberculosis (TB); 93.8% ( n = 334) of the IGRA results were negative and 4.2% ( n = 15) were indeterminate. Among those with indeterminate results, 66.7% ( n = 10) were undergoing corticosteroid treatment. The remaining 2.0% ( n = 7) had a positive IGRA test result. None of the CXRs performed revealed any radiological signs of TB disease. None of these patients had TB reactivation after immunosuppresion. Conclusion Routinely performing a CXR in individuals with a negative IGRA offers limited benefits, and submits patients to unnecessary radiation.

Background and purpose Low grade tumors (LGT) are the most frequent central nervous system lesions observed in children. Despite the high-throughput research, differentiating LGT from tumor- like lesions (TLL) and providing an accurate differential diagnosis based on conventional MRI remains a challenge. For this reason, advanced MR sequences are routinely investigated and applied in clinical practice. The aim of this study is to explore the potential of the amide proton transfer (APTw) sequence as a tool for discriminating LGT from TLL. Materials and methods In this single-center retrospective study, we recruited 35 patients (20 with a histologically confirmed LGT, and 15 with a TLL) with both conventional and APT MRI images obtained on a 3T clinical scanner at onset or prior to treatment/surgery. Two volumes of interest (VOI), namely the whole lesion and the normal appearing white matter (NAWM), were defined using the semi-automatic segmentation tool from Philips Intellispace portal for Windows (v. 8). The mean APTw (mAPTw) and difference between the mAPTw lesion and the NAWM (dAPTw) were measured and compared between the two groups. Results Lower values were found in the TLL group compared to the LGT group for both the mAPTw (1.51 ± 0.64% vs. 2.87 ± 0.96%) and dAPTw (0.24 ± 0.72% vs. 1.53 ± 1.08%) (p-value < 0.001). Based on ROC curve analysis, optimal cut-offs value for mAPTw and dATPw were 1.79 and 0.53, respectively. Conclusion APT imaging may prove useful to discriminate between LGT and TLL in pediatric patients.

Introduction Racial and ethnic disparities in obstetrics persist globally despite improvements in maternal mortality rates and are related to access, experience and outcomes. We aimed to elucidate the racial and ethnic disparity in obstetric analgesia and anaesthesia. Methods Databases were searched and we included studies published in the English language conducted in all countries. Search terms included terminology concerning obstetric anaesthesia related to race or ethnicity. Included papers were assessed for risk of bias. Studies were included for detailed review if they described disparities relating to obstetric anaesthesia between two or more racial or ethnic groups. Results In total, 1806 abstracts were screened of which 25 articles were included and data from 19 could be pooled for meta‐analysis using a random effects model. Outcome measures included disparities in labour neuraxial analgesia utilisation and general anaesthesia use for caesarean delivery. Sixteen observational studies examined labour neuraxial analgesia, representing data from 13,398,421 patients in the USA and UK. Patients categorised as Asian or Black had lower odds of receiving neuraxial analgesia when compared with those from White backgrounds (odds ratios (95%CI) 0.80 (0.65–0.99) and 0.72 (0.61–0.85), respectively). Six studies examined the use of general anaesthesia for caesarean delivery in 2,139,763 patients. Black patients were more likely to receive general anaesthesia compared with White patients (odds ratio (95%CI) 1.60 (1.15–2.22)). Risk of bias assessments showed high or very high risk of bias in 13 of the 25 included studies. Discussion Racial and ethnic disparities exist in obstetric anaesthesia. Further research to elucidate causes and ongoing action to minimise them are crucial.

Background Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a multifactorial inflammatory disorder of the gastrointestinal system that impairs the patient’s quality of life. Its presentation includes a spectrum of symptoms that may also be secondary to IBD complications, such as malignancy. On the other hand, immunosuppressive treatment to maintain remission also carries a risk of malignancy, which can cause patients distress due to the risk/benefit balance of IBD control and malignancy. Methods In this nationwide retrospective study, we aimed to elucidate which patient and treatment factors have the greatest impact on the development of malignancy in IBD patients. Statistical analysis was performed on patient factors, including treatment types, and nominal regression analysis was carried out to assess the effects of multiple risk factors on the incidence of malignancy in patients with IBD. Results Age at diagnosis of IBD correlated significantly with malignancy development, as did the diagnosis of ulcerative colitis. IBD patients diagnosed with malignancy had an older age of onset of IBD than those who did not develop malignancy. Sex, treatment type, treatment duration, and extent or location of disease did not correlate significantly with malignancy development. Conclusion We conclude that age of onset of IBD plays the greatest role in malignancy development, whilst immunosuppressive treatment is not a significant risk factor.

Fontan-associated liver disease (FALD) is a significant complication in patients with Fontan palliation. The improved longevity following Fontan palliation has led to wider recognition of FALD and its association with hepatocellular carcinoma (HCC). This review examines the intricate link between FALD and HCC development, emphasizing the unique hemodynamic changes in Fontan circulation that promote hepatic congestion, fibrosis and cirrhosis, thereby facilitating carcinogenesis. The review comprehensively analyzes the existing literature, highlighting key risk factors, pathophysiological mechanisms, and diagnostic challenges in FALD-related HCC. While HCC incidence in FALD remains relatively low (1.5-5.0%), its higher mortality rate of 29.4% necessitates a thorough understanding of contributing factors and screening requirements. The management of FALD involves multidisciplinary approaches, addressing cardiac and hepatic aspects, with regular surveillance for liver disease progression and HCC using advanced imaging and biomarkers. Therapeutic considerations include interventions to manage hepatic congestion and fibrosis, although balancing these with the unique cardiac needs of Fontan circulation remains challenging. Interestingly, FALD management often mirrors that of other liver diseases, underscoring the need for tailored approaches. In severe cases, combined heart–liver transplantation offers a comprehensive solution for FALD-HCC. This review consolidates current knowledge on the epidemiology, pathogenesis and comprehensive management of HCC in the specific context of FALD, ultimately improving outcomes for this unique patient population.