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INTRODUCTION:Upper gastrointestinal (UGI) cancers, comprising malignancies of the esophagus, stomach, duodenum, pancreas, liver, biliary tract, and gallbladder, are the second leading cause of cancer-related mortality in the United States and are associated with significant comorbidities. Recent studies show a disproportionate rise in pancreatic and stomach cancer among young adults. This study aims to use a nationwide, population-based cohort to (i) evaluate the trend of all UGI cancer as an aggregate and (ii) examine the role of demographics, histology, and tumor stage in UGI cancer incidence among young adults.METHODS:Individuals diagnosed with UGI cancer in the United States from 2001 to 2019 were identified and obtained from the Surveillance, Epidemiology, and End Results-National Program of Cancer Registries database. The primary outcomes were incidence rates of UGI cancer (calculated per 100,000, age-adjusted to the year 2000 US population), stratified by sex and age (< 55 years for young adults and ≥ 55 years for older adults). Trends, annual percentage change, and average annual percentage change were calculated using the parametric method. Sensitivity analysis was performed according to primary site and histology; further analysis examining race and cancer stage was performed in the young adult subgroup.RESULTS:A total of 2,333,161 patients with UGI cancer were identified. Most cases were male, and 14.3% were < 55 years of age. Incidence of UGI cancer increased most in women younger than 55 years, driven primarily by pancreatic and stomach cancers, as well as neuroendocrine tumor and gastrointestinal stromal tumor histology. African American race and localized tumors and malignancy with distant spread are also contributing to the disparate increase among young women. UGI mortality rates have not changed significantly in young adults.DISCUSSION:The overall incidence rate of upper gastrointestinal cancer is increasing significantly in young women compared with men. Increased endoscopic procedures and disparate exposure to risk factors are likely contributing to these trends.

Surgical clip migration into the common bile duct (CBD) with subsequent stone formation is an exceedingly rare complication following both laparoscopic and open cholecystectomy, with fewer than 100 cases reported in the literature. Herein, we present the case of a 78-year-old female who presented with abdominal pain and dark urine six years after an open cholecystectomy. Her abdominal ultrasonography revealed no abnormalities, with only mild derangements noted in liver function tests. However, computed tomography of the abdomen unveiled a single metallic surgical clip lodged within the CBD, surrounded by a bile stone, alongside another clip at the gallbladder fossa. The patient underwent endoscopic retrograde cholangiopancreatography (ERCP), during which the clip was successfully removed. The procedure has utilized SpyGlass cholangioscopy. While clip migration into the CBD remains a rare phenomenon, it should be considered in the differential diagnosis of patients presenting with obstructive jaundice or biliary colic post-cholecystectomy. Minimally invasive management by ERCP is the procedure of choice for migrated clips-related complications but surgical common bile duct exploration may be necessary. This case highlights the importance of vigilance and prompt intervention in managing post-cholecystectomy clip migration (PCCM) but potentially serious postoperative complications.

This case report explores the complex clinical trajectory of a 72-year-old female with a history of hypertension, iron-deficiency anaemia, and vertigo, who underwent an endoscopic retrograde cholangiopancreaticography (ERCP) procedure for common bile duct (CBD) stone removal. After an uneventful laparoscopic cholecystectomy, she continued to experience abdominal pain and icterus. Investigations including magnetic resonance cholangiopancreatography (MRCP), revealed a dilated CBD with multiple stones, prompting ERCP. During the procedure, a fall in saturation and arrhythmia were noted, leading to the diagnosis of gas embolism. Trans-esophageal echocardiography (TEE) confirmed air bubbles in cardiac chambers and a patent foramen ovale (PFO). Despite interventions, including intubation, noradrenaline infusion, and a temporary pacemaker, the patient's cardiovascular status deteriorated. Due to financial constraints, she was discharged against medical advice (DAMA) with a high-risk profile. This case highlights the rarity and iatrogenic nature of ERCP-related air embolism, emphasising the challenges in its management and underscoring the need for awareness and timely intervention. The discussion delves into the broader context of air embolism pathogenesis, referencing relevant literature and highlighting the need for continued research in managing such rare complications associated with ERCP.

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants’ next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals ( n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones’ altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK.

Little is known about the effects of HIV reservoir research at the end of life on staff members involved. Staff members' perceptions and experiences were assessed related to their involvement in the Last Gift, a rapid autopsy study at the University of California San Diego enrolling people living with HIV who are terminally ill and have a desire to contribute to HIV cure-related research. Two focus group discussions consisting of clinical (n = 7) and rapid research autopsy (n = 8) staff members were conducted to understand the perspectives of staff members and the impact the Last Gift rapid autopsy study had on them. The total sample consisted of 66.7% females and 33.3% males and was ethnically diverse (66.7% Caucasian, 6.7% African American, 20.0% Asian descent, 6.7% Hispanic descent and American Indian) with a range of experience in the HIV field from 1 year to 30 years. Qualitative focus group data revealed five major themes underlying study staff members' multilayered mental and practical involvement: 1) positive perceptions of the Last Gift study, with sub-themes including Last Gift study participants' altruism, fulfillment, and control at the end of life, 2) perceptions of staff members' close involvement in the Last Gift study, with sub-themes related to staff members' cognitive processing, self-actualization and fulfillment, stress management and resilience, coping mechanisms, and gratitude toward Last Gift participants and toward the study itself, 3) considerations for successful and sustainable study implementation, such as ethical awareness and sustained community and patient engagement, 4) collaborative learning and organizational processes and the value of interdependence between staff members, and 5) considerations for potential study scale-up at other clinical research sites. Understanding staff members' nuanced emotional and procedural experiences is crucial to the Last Gift study's sustainability and will inform similar cure research studies conducted with people living with HIV at the end of life. The study's potential reproducibility depends on a robust research infrastructure with established, interdependent clinical and rapid autopsy teams, continuous community engagement, and an ethical and well-informed engagement process with people living with HIV.

Bacillus Calmette-Guerin (BCG) vaccine is a type of immunomodulatory drug which is not only used for prevention of pulmonary and extrapulmonary tuberculosis but also in treatment of urinary bladder cancer. It is administered intravescicular into the bladder and acts by decreasing the growth of tumour by cicatrisation and immune system activation.1,2 However, it has been reported previously that in rare situations, it may get absorbed into the system of the individual and spread via bloodstream. This can lead to a widespread systemic inflammation in place of what should have been a local reaction and can lead to a vaccine induced potentially fatal condition called BCGitis or BCGosis.3,4 Here we describe a case of 83 year old gentleman who was admitted with complains of generalised fatigue and weakness since 4–6 months, confusion and reduced mobility since 3–4 weeks. His daughter also complained of him having a chronic cough since 4 weeks (ex smoker). He had a background history of squamous cell carcinoma of urinary bladder (diagnosed in 2022), receiving intravescicle BCG vaccine since then (1.5 years), diabetes mellitus, hypertension, permanent pacemaker in situ and Chronic Myeloid Leukemia. His travel history included a recent trip to Spain with his daughter, after which his symptoms worsened progressively. He was seen by a respiratory consultant in an outpatient appointment 2 weeks prior his admission and raised concerns about perihilar and pretracheal lymphadenopathy on his CT Thorax and was investigated them due to BG of CML and bladder cancer. After a MDT and discussion with Haematologist, a PET CT was done as an inpatient. Images of which can be seen here (Image 1 and 2). ▪ The PET-CT was reported as- ‘There are multiple enlarged mediastinal and hilar nodes with paratracheal nodes measuring up to 10 mm (previously 8.6 mm), precarinal nodes measuring up to 13 mm (previously 8.7 mm), subcarinal nodes measuring up to 18 mm (previously 14 mm) and hilar conglomerate nodes bilaterally.’ An ultrasound guided biopsy of one of the lymph nodes done as an IP was reported as- ‘Core biopsies of lymph node showing non-necrotising granulomatous inflammation.Granulomata are composed of epithelioid histiocytes and occasional multinucleate giant cells. Mostly small lymphocytes are seen between follicles with some medium sized immunoblastic cells and plasma cells. No atypical large cells are seen. Final Diagnosis:Right supraclavicular lymph node biopsy:- Non-necrotising granulomatous inflammation.’ He was started on anti tubercular treatment but soon developed sepsis secondary to a HAP and unfortunately succumbed to his illness. Such instances of vaccine induced BCGosis hav been described previously. One such report by Katarzyna Lewandowska et al. was published in 2022.5 Another case (Shai Shrot et al. in 2016) reported BCGosis in children with primary immunodeficiencies.6 This case report was chosen to be discussed as this highlights the importance of basics in medicine such as a detailed history taking (including treatment history). This case also teaches us importance of good communication, effective MDTs and team work.

Glioblastoma multiforme (GBM) is a World Health Organisation (WHO) grade IV glioma originating from astrocytes. It is the most common malignant primary tumour of the brain and central nervous system (CNS) and is associated with fast progression and violent local spread, with a median overall survival of approximately 15 months after diagnosis. Due to its late and varied presentation, it is often diagnosed only after it has grown considerably. The symptomatology can vary from the individual being completely asymptomatic to mild sensory or sensorimotor symptoms. The symptoms usually arise due to compression of the fibres rather than pressure on vital structures.  We discuss a case of a 72-year-old male who presented with complaints of tingling in the left upper limb for one day, improving spontaneously. A noncontrast CT head was nondiagnostic, and an MRI reported a likely metastatic lesion, and further imaging was advised. A detailed history was taken from an oncology point of view but the patient denied any weight loss, fever, recent travel, and family history of cancers. The scans were discussed at a neuroradiology multidisciplinary team (MDT) discussion an MRI with contrast was planned. After a thorough discussion and further review by neuroradiology consultants, the patient was diagnosed with a grade IV glioblastoma - a primary tumour of the brain - which was confirmed by a biopsy and immunohistochemistry. He was treated with two cycles of radiotherapy initially, followed by chemotherapy. Unfortunately, he died eight months after the start of the treatment due to a massive pulmonary embolism, complicated by nosocomial infection. This report highlights the importance of early diagnosis and treatment for patients with glioma. It also sheds light on the symptomatology and difficulties faced in the diagnosis of gliomas. Treating physicians should adopt an MDT approach in such cases and discuss the various possibilities and differentials.

Background The U.S. National Institute of Allergies and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) have a new research priority: inclusion of terminally ill persons living with HIV (PLWHIV) in HIV cure-related research. For example, the Last Gift is a clinical research study at the University of California San Diego (UCSD) for PLWHIV who have a terminal illness, with a prognosis of less than 6 months. Discussion As end-of-life (EOL) HIV cure research is relatively new, the scientific community has a timely opportunity to examine the related ethical challenges. Following an extensive review of the EOL and HIV cure research ethics literature, combined with deliberation from various stakeholders (biomedical researchers, PLWHIV, bioethicists, and socio-behavioral scientists) and our experience with the Last Gift study to date, we outline considerations to ensure that such research with terminally ill PLWHIV remains ethical, focusing on five topics: 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining a favorable benefits/risks balance, 4) safeguarding against vulnerability through patient-participant centeredness, and 5) ensuring the acceptance of next-of-kin/loved ones and community stakeholders. Conclusion EOL HIV cure-related research can be performed ethically and effectively by anticipating key issues that may arise. While not unique to the fields of EOL or HIV cure-related research, the considerations highlighted can help us support a new research approach. We must honor the lives of PLWHIV whose involvement in research can provide the knowledge needed to achieve the dream of making HIV infection curable.

Background and Aims Antibodies targeting bacterial cytolethal distending toxin subunit B (CdtB) and vinculin are diagnostic of post-infection irritable bowel syndrome (IBS). In this study, we explored the temporal behavior of anti-CdtB and anti-vinculin antibodies and potential relationships to IBS symptoms. The potential impacts of antibody reduction therapies were also assessed. Methods A retrospective chart review of 417 IBS patients who had been tested for anti-CdtB and anti-vinculin antibodies was performed. Anti-vinculin and anti-CdtB antibody levels, time to normalization of antibody levels, and IBS symptoms’ burdens and changes were assessed. Use of antibody-depleting therapies (intravenous immunoglobulin [IVIG] or plasmapheresis exchange [PLEX]) vs. usual management was also recorded. Results 158 subjects (38.5%) were positive for either anti-CdtB or anti-vinculin. In subjects with multiple tests (total N  = 38), normalization of anti-vinculin levels over time correlated with improvements in IBS symptoms ( p  = 0.020). Plasmapheresis (PLEX) or intravenous immunoglobulins (IVIG) treatments were associated with greater antibody normalization than usual management ( p  = 0.046). Conclusions Anti-CdtB and anti-vinculin antibodies are common in post-infection IBS, and anti-vinculin levels may correlate with severity of IBS symptoms.