Pituitary hypophysitis in granulomatosis with polyangiitis (GPA): a case series.

Granulomatosis with polyangiitis (GPA) rarely involves the pituitary gland. Pituitary involvement has been reported in ~ 1% of all cases of GPA. Most commonly, pituitary swelling and inflammation results in symptoms due to pituitary mass effect and arginine vasopressin deficiency. To date, there are no pituitary-specific treatment guidelines for this rare condition. We present three patients with GPA-related hypophysitis highlighting the spectrum of pituitary involvement. All three patients were successfully treated with immunosuppressive regimens that included rituximab (RTX). Following remission induction with high-dose glucocorticoids, patients received 6 monthly RTX for remission maintenance. RTX was well tolerated without significant side effects.

LGI1 Encephalitis and IgG4-Related Disease: Rare Conditions Collide.

OBJECTIVES: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis and IgG4-related disease (IgG4RD) have traditionally been regarded as 2 distinct disease entities. METHODS: We detail the presentation, investigations, and management of a patient who showed typical signs and symptoms of LGI1 encephalitis and also found to possess pancreatic changes and a serum profile in keeping with IgG4RD. RESULTS: Serum and CSF analyses at presentation showed a significant hyponatraemia (117 mmol/L), elevated IgG4 concentration (1.73 g/L), and the presence of LGI1 antibodies. MRI revealed symmetrical diffuse T2-weighted hyperintensity and mild swelling throughout both medial temporal lobes. CT of the chest, abdomen and pelvis revealed an edematous, bulky pancreas with loss of lobulation, typical for IgG4RD. A glucocorticoid weaning regimen was commenced, facilitated by 2 rituximab infusions, with the patient showing an effective treatment response. HLA testing confirmed the presence of HLA DRB1 and HLA DQB1 risk alleles. DISCUSSION: This case suggests that there may be shared mechanisms between LGI1 encephalitis and IgG4RD, supported by common risk HLA associations and treatment strategies/responses. To our knowledge, this represents the first instance that LGI1 encephalitis and IgG4RD have been reported in the same patient and emphasizes the continued development of our understanding of the wide range of IgG4-mediated conditions.

Innovation in gastrointestinal surgery: the evolution of minimally invasive surgery-a narrative review.

Background: Minimally invasive (MI) surgery has revolutionised surgery, becoming the standard of care in many countries around the globe. Observed benefits over traditional open surgery include reduced pain, shorter hospital stay, and decreased recovery time. Gastrointestinal surgery in particular was an early adaptor to both laparoscopic and robotic surgery. Within this review, we provide a comprehensive overview of the evolution of minimally invasive gastrointestinal surgery and a critical outlook on the evidence surrounding its effectiveness and safety. Methods: A literature review was conducted to identify relevant articles for the topic of this review. The literature search was performed using Medical Subject Heading terms on PubMed. The methodology for evidence synthesis was in line with the four steps for narrative reviews outlined in current literature. The key words used were minimally invasive, robotic, laparoscopic colorectal, colon, rectal surgery. Conclusion: The introduction of minimally surgery has revolutionised patient care. Despite the evidence supporting this technique in gastrointestinal surgery, several controversies remain. Here we discuss some of them; the lack of high level evidence regarding the oncological outcomes of TaTME and lack of supporting evidence for robotic colorectalrectal surgery and upper GI surgery. These controversies open pathways for future research opportunities with RCTs focusing on comparing robotic to laparoscopic with different primary outcomes including ergonomics and surgeon comfort.

Learning Curves in Establishing a New Minimally Invasive Pancreas Program.

INTRODUCTION: Robotic pancreaticoduodenectomy (rPD) is a complex operation with a reported learning curve of 80 cases. Two recent graduates of a formal robotic complex general surgical oncology training program have been performing rPD at our institution since 2016, which had no previous institutional experience with rPD. OBJECTIVE: To evaluate the learning curve associated with developing a new robotic pancreaticoduodenectomy (rPD) program by fellowship trained surgeons with institutional support. METHODS: Sixty patients undergoing rPD from 2016 to 2022 were reviewed for and compared with proficiency benchmarks set by the University of Pittsburg experience. RESULTS: By 30 cases, operative time met the proficiency benchmark of 391 minutes. Additionally, the entire cohort had comparable rates of clinically relevant postoperative pancreatic fistula (6.7% vs 3%, P = .6), 30-day mortality (0% vs 3%, P = .18), major complications (Clavien >2; 23% vs 17%, P = .14), and length of stay (6 vs 7 days, P = .49) when compared to the benchmark. CONCLUSION: Perioperative outcomes were comparable to proficiency benchmarks from initiation of the new rPD program, and operative time reached proficiency benchmark by 30 cases. This data suggests that graduates of formal rPD training programs can safely establish new minimally invasive pancreas programs at sites with no previous institutional rPD experience.

Can educational video resources improve learning when used to augment traditional teaching of clinical examination? A randomized control trial of novice medical students.

BACKGROUND: Good clinical examination skills can both increase the quality of patient care and reduce its cost. A previous study by our group demonstrated that face-to-face training is the gold standard for teaching these skills. It is unclear if high quality educational videos can augment this teaching. METHODS: Forty-two Medical Students naïve to large joint examination were recruited and block randomised to two groups. The control group had face-to-face teaching alone. The intervention group had their teaching augmented with a custom educational video accessed via a web portal. Participants were assessed on their examination of a large joint using a previously standardised assessment tool at baseline and 7 days post intervention. Assessors were blinded to intervention type. RESULTS: There was no significant difference in the mean baseline scores. Mean baseline scores were 3.35 (11.2%, SD = 2.2, SE = 0.49) for the face-to-face only group and 2.65 (8.8%, SD = 1.39, SE = 0.31) for the video adjunct group [p = 0.137]. There was a significant difference in the improvement in score after intervention between each group [p = 0.005]. The mean improvement in score was 15.42 (SD = 5.64, SE = 1.29) for the face-to-face only group and 20.68 (SD = 4.33,SE = 0.99) for the video adjunct group. CONCLUSION: When used as an adjunct to more traditional face-to-face teaching methods, a custom-made educational video significantly improves the teaching of clinical examination skills and there is a role for these resources in augmenting traditional teaching methods.

Robotic versus open pancreaticoduodenectomy in elderly patients: a propensity score-matched analysis.

BACKGROUND: Pancreaticoduodenectomy (PD) is complex procedure with high morbidity in the elderly. This retrospective study aimed to compare post-operative outcomes in patients ≥75 years of age who underwent robot-assisted (RA)PD and open PD. METHODS: We analyzed 2502 patients ≥75 years of age who underwent PD from 2015 to 2018 in the National Surgical Quality Improvement Program (NSQIP) database. RAPD and open PD patients were propensity score matched 1:5 to assess the 30-day outcomes of interest: postoperative complications, length of stay, discharge destination, and readmissions. RESULTS: Of 725 matched patients, 110 underwent RAPD, 615 OPD, and 12 were converted to an open operation. Post-operative outcomes were largely similar between cohorts. RAPD was associated a shorter length of stay (median 8 days, interquartile range [IQR] 6 to 11) than OPD (median 8 days, IQR 7 to 13) (p = 0.003). However, RAPD was associated with more readmissions (28.1% vs. 17.7%; p = 0.02). CONCLUSIONS: RAPD in patients ≥75 years of age appears to be safe and has a similar complication profile to open PD. Randomized or well-designed prospective matched studies are needed to confirm these findings.

Gender Differences in Experiences and Expectations of Hemodialysis in a Frail and Seriously Unwell Patient Population.

Introduction: Surprisingly few studies have explored the experiences of seriously unwell people with kidney disease on hemodialysis therapy: we conducted a mixed-methods study to investigate gender differences in illness experience, symptom burden, treatment considerations or expectations in this cohort. Methods: Seriously unwell people on hemodialysis (1-year mortality risk of >20%) at 3 hospital-based units were invited to take part in a structured interview or to complete the same questions independently via a questionnaire. A total of 54 people took part (36 males, 18 females); data analysis was undertaken using a thematic approach. Results: "Desire to keep living" is the most important and basic thought process when starting dialysis. Fear also predominates influencing risk assessment and decision-making. Once fear is managed, there are physical, social, practical and emotional issues to rationalize, but choice only seems possible if shared decision-making is part of the consultation.Gender differences were seen in perceived hopes and expectations of treatment. Males were more likely to prioritize achievement of physical goals, with females prioritizing a wish to feel well. Both genders reported significantly higher symptom scores than their health care provider perceived, however this difference was more marked in females. Dialysis regret existed in >50% of participants and 6 out of 54 (11%) stated that they would have chosen no dialysis at all. Females were more likely to report feeling depressed (P = 0.001). Conclusion: Different genders approach treatment decisions and prioritize treatment expectations differently. Recognizing this will allow personalized care plans to be developed and improve the experiences of seriously unwell people with kidney disease.

Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer.

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

Small vessel vasculitis associated with culture-negative infective endocarditis related to a cardiac device: a case report.

Background: Culture-negative endocarditis is uncommon, occurring in less than a third of all cases of infective endocarditis (IE). Culture-negative IE related to a cardiac device is an even greater diagnostic challenge due to its insidious presentation, with onset of symptoms ranging between 3 and 12 months after device implantation. Sensitivity of the modified Duke's criteria remains low in culture-negative and cardiac device-related IE (CDRIE) since classical signs and symptoms of IE are often absent. Small vessel vasculitis has been reported as an immune response to IE. Recognizing immunological phenomenon related to IE is of paramount clinical importance, prompting the search for an underlying infection and avoiding the use of immunosuppressive medications which would otherwise result in an adverse outcome. Case summary: An 81-year-old Caucasian male presented to the ambulatory medical unit with a two-week history of a symmetrical, generalized purpuric rash. He had an indwelling permanent pacemaker following a transcatheter aortic valve implantation for severe aortic stenosis five years ago. Blood tests showed an iron deficiency anaemia, thrombocytopenia and normal renal function, both CRP and ESR were raised at 61  and 30 mm/hr, respectively. Skin biopsy demonstrated small vessel cutaneous vasculitis. Transthoracic echocardiography revealed a mobile mass measuring 0.9 × 1.7 cm, confirmed on transoesophageal echocardiogram as pacing lead endocarditis. Blood cultures were persistently negative. The patient underwent pacemaker lead extraction, following which the vasculitic rash improved. Discussion: Blood cultures in IE are more likely to be negative if there is a prior antibiotic administration or causative micro-organisms with limited proliferation which fail to grow in conventional media conditions. Transesophageal echocardiography (TOE) offers improved sensitivity and diagnostic yield when compared to transthoracic echocardiography (TTE) in patients with a high clinical suspicion of CDRIE. The evidence in the literature describing culture-negative IE associated with small vessel vasculitis is limited. However, it is recognized that cutaneous small vessel vasculitis may be associated with an underlying bacterial infection. IE produces an inflammatory response, resulting in the deposition of circulating immune complexes and cutaneous signs which are included in the modified Duke's criteria to aid diagnosis. Management of CDRIE requires a multi-disciplinary team approach with an 'Endocarditis Team.' Pacemaker lead infection requires transvenous lead extraction if it is a newly implanted lead. Locking stylets, extraction sheaths or snare retrieval are usually required in cases of older implanted leads. Surgical lead extraction remains the gold standard for larger vegetations (>20 mm) or associated valve endocarditis.

Duration of External Neck Stabilisation (DENS) following odontoid fracture in older or frail adults: protocol for a randomised controlled trial of collar versus no collar.

INTRODUCTION: Fractures of the odontoid process frequently result from low impact falls in frail or older adults. These are increasing in incidence and importance as the population ages. In the UK, odontoid fractures in older adults are usually managed in hard collars to immobilise the fracture and promote bony healing. However, bony healing does not always occur in older adults, and bony healing is not associated with quality of life, functional, or pain outcomes. Further, hard collars can cause complications such as skin pressure ulcers, swallowing difficulties and difficulties with personal care. We hypothesise that management with no immobilisation may be superior to management in a hard collar for older or frail adults with odontoid fractures. METHODS AND ANALYSES: This is the protocol for the Duration of External Neck Stabilisation (DENS) trial-a non-blinded randomised controlled trial comparing management in a hard collar with management without a collar for older (≥65 years) or frail (Rockwood Clinical Frailty Scale ≥5) adults with a new odontoid fracture. 887 neurologically intact participants with any odontoid process fracture type will be randomised to continuing with a hard collar (standard care) or removal of the collar (intervention). The primary outcome is quality of life measured using the EQ-5D-5L at 12 weeks. Secondary outcomes include pain scores, neck disability index, health and social care use and costs, and mortality. ETHICS AND DISSEMINATION: Informed consent for participation will be sought from those able to provide it. We will also include those who lack capacity to ensure representativeness of frail and acutely unwell older adults. Results will be disseminated via scientific publication, lay summary, and visual abstract. The DENS trial received a favourable ethical opinion from the Scotland A Research Ethics Committee (21/SS/0036) and the Leeds West Research Ethics Committee (21/YH/0141). TRIAL REGISTRATION NUMBER: NCT04895644.

Coupling Lipid Labeling and Click Chemistry Enables Isolation of Extracellular Vesicles for Noninvasive Detection of Oncogenic Gene Alterations.

Well-preserved molecular cargo in circulating extracellular vesicles (EVs) offers an ideal material for detecting oncogenic gene alterations in cancer patients, providing a noninvasive diagnostic solution for detection of disease status and monitoring treatment response. Therefore, technologies that conveniently isolate EVs with sufficient efficiency are desperately needed. Here, a lipid labeling and click chemistry-based EV capture platform ("Click Beads"), which is ideal for EV message ribonucleic acid (mRNA) assays due to its efficient, convenient, and rapid purification of EVs, enabling downstream molecular quantification using reverse transcription digital polymerase chain reaction (RT-dPCR) is described and demonstrated. Ewing sarcoma protein (EWS) gene rearrangements and kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation status are detected and quantified using EVs isolated by Click Beads and matched with those identified in biopsy specimens from Ewing sarcoma or pancreatic cancer patients. Moreover, the quantification of gene alterations can be used for monitoring treatment responses and disease progression.

Circulating Fatty Objects and Their Preferential Presence in Pancreatic Cancer Patient Blood Samples.

Human cancers are often complicated with increased incidences of blood vessel occlusion, which are mostly insensitive to anticoagulation therapy. We searched for causal factors of cancer-associated embolism. A total of 2,017 blood samples was examined for visible abnormalities. Examined were peripheral blood samples from cancer patients who were about to undergo surgical treatment for genitourinary, breast, gastrointestinal or abdominal tumors. Samples from ambulatory patients being treated for recurrent or castration-resistant prostate cancers were included in the study. The lipid-rich nature was studied with lipophilic stains and lipid panel analysis, while surface membrane was assessed with specific staining and antibody detection. We identified a new entity, lipid droplet-like objects or circulating fatty objects (CFOs), visible in the blood samples of many cancer patients, with the potential of causing embolism. CFOs were defined as lipid-rich objects with a membrane, capable of gaining in volume through interaction with peripheral blood mononuclear cells in ex vivo culture. Blood samples from pancreatic cancer patients were found to have the highest CFO incidence and largest CFO numbers. Most noticeably, CFOs from many pancreatic cancer samples presented as large clusters entangled in insoluble fiber networks, suggestive of intravascular clotting. This study identifies CFO as an abnormal entity in cancer patient blood, and a contributory factor to intravascular embolism during cancer development and progression.

A systematic review of methodological principles and delivery of surgical simulation bootcamps.

BACKGROUND: The growth of "bootcamp style" simulation training in surgical practice has been exponential over the last decade. Developing and delivering a surgical bootcamp requires a significant investment. This systematic review aims to identify the key components that allow for a successful and rewarding surgical bootcamp course to be implemented that can be applied to all surgical specialities. METHODS: To understand the surgical bootcamp principles and delivery mechanisms, we searched peer-reviewed, English language studies published between 2000 and 21. RESULTS: From 137 articles, 14 studies with a Medical Education Research Quality Instrument Score of >11.5 were included. Most studies followed the core components; delivery at transition (12), mapping syllabus (13), multimodality delivery (14), and deliberate practice with formative feedback (12) apart from 1:1 training by only 2 studies. CONCLUSIONS: Our review suggests that Surgical bootcamp can be an extremely useful education tool for trainees if 5 pillars of a boot camp are respected.

Assessing tradeoffs in the design of climate change adaptation strategies for water utilities in Chile.

Climate change is a challenge to drinking water providers worldwide and to regulatory frameworks that consider long-term investment decisions. Coping with an unstable climate warrants adjustments in regulations and new investments. The investment required to maintain a selected service level needs to balance the potential for high regret stranded assets with the political and socioeconomic consequences of not meeting water demands. In recent years, the City of Santiago in Chile has seen drought events associated with climate change, which could worsen in the future. Chile's drinking water regulatory framework does not account for uncertainty in infrastructure design to cope with the potential impacts of such events. This work presents an adaptation option design process that considers multiple plausible climate change-impacted future scenarios, accommodating both structural and nonstructural measures. In our Santiago case study adaptation measures include extensions to the existing Chilean water market and traditional structural alternatives (e.g., storage infrastructure); all are represented in a simulation model of the water utility. We evaluate and optimize packages of efficient adaptation measures for various climate scenarios. This allows comparing different portfolios of combined institutional and infrastructure interventions via a range of stakeholder measures and comparing their tradeoffs under different plausible climate-impacted hydrological scenarios. Results showed that water supply performance without climate change adaptation is worse under climate scenarios with lower water availability, which are likely to be associated with higher GHG emission scenarios such as RCP 8.5. The optimized portfolios implement various combinations of adaptation strategies to reduce the impacts of this poor performance. Considering the uncertainty on future climate scenarios, the use of nonstructural adaptation measures such as option contracts exhibits the advantage of providing water in critical periods while avoiding large investments such as building reservoirs or the purchase of permanent water rights, which could end up underused if favorable climate scenarios manifest.

Management of C2 odontoid peg fragility fractures - A UK survey of spinal surgeons.

PURPOSE: Patients sustaining fragility fractures of the C2 odontoid peg have 30-day mortality rates as high as 10% rising up to 34.1% at 1 year. Substantial controversy exists regarding optimal management of these fractures and there is a lack of national guidance to inform best practice. The aim of this study was to determine current practice in the management of these fractures throughout the United Kingdom. METHODS: A UK wide, cross sectional survey was conducted, asking 10 questions regarding the initial management, imaging and follow-up of an elderly patient with a type 2 fragility odontoid peg fracture. This was publicised through the British Orthopaedic Association website and sent to all members of the Society of British Neurological Surgeons (SBNS) via email. RESULTS: 107 Responses were received. 56% from orthopaedic consultants, 29% from neurosurgical consultants and 15% from senior spine fellows. 86% (92) of respondents choose treatment with a cervical orthosis, with 84% (77) of these opting for a semi rigid Aspen or Philadelphia collar compared to 16% (15) opting for a soft cervical collar. Three (3%) opted for operative intervention with a further three (3%) choosing Halo fixation. Nine respondents (8%) opted for no orthosis and treatment with analgesia alone. Length of immobilisation in cervical orthosis ranged from 6 to 12 weeks. Initial follow-up ranged from 1 week to 6 weeks, with 6% (6) discharged without follow up. There was also marked variation in the use of follow-up imaging with 17% (18) using plain radiographs, 62% (66) requesting lateral flexion / extension radiographs, 10% (11) using CT and 11% (12) not performing any imaging at final follow up. In 60% (64) of cases respondents did not change subsequent management as a result of imaging. CONCLUSION: Type-2 fragility peg fractures have high morbidity and mortality. There is marked variation in the treatment modalities used, follow-up regime and use of imaging throughout the UK. Given the rapidly increasing incidence of these injuries and the associated mortality this should be a high priority field for further research. Further large scale studies are urgently required to inform best practice and standardise management of these injuries.

Perceptions of Illness Severity, Treatment Goals, and Life Expectancy: The ePISTLE Study.

INTRODUCTION: A better understanding of factors influencing perceived life expectancy (PLE), interactions between patient prognostic beliefs, experiences of illness, and treatment behavior is urgently needed. METHODS: Case-notes at 3 hemodialysis units were screened: patients with ≥20% 1-year mortality risk were included. Patients and their health care professionals (HCPs) were invited to complete a structured interview or mixed-methods questionnaire. Four hundred eleven patient notes were screened. Seventy-seven eligible patients were approached and 51 were included. RESULTS: Patients predicted significantly higher life expectancies than HCPs (P < 0.0001). Documented cognitive impairment, gender, or increasing age did not affect 1- or 5-year PLE. PLE influenced priorities of care: one-fifth of patients who estimated themselves to have >95% 1-year survival preferred "care focusing on relieving pain and discomfort," compared with nearly three-quarters of those reporting a ≤50% chance of 1-year survival. Twenty of 51 (39%) patients believed transplantation was an option for them, despite only 4 being waitlisted at the time of the interview. Patients who thought they were transplant candidates were significantly more confident they would be alive at 1 and 5 years and to want resuscitation attempted. Cognitive impairment had no effect on perceived transplant candidacy. A high symptom burden was present and underrecognized by HCPs. High symptom burden was associated with significantly lower PLE at both 1 and 5 years, increased anxiety/depression scores, and treatment choices more likely to prioritize relief of suffering. CONCLUSION: There is a disparity between patient PLE and those of their HCPs. Severity of symptom burden and beliefs regarding PLE or transplant candidacy affect patient treatment preferences.

The mixed reality medical ward round with the MS HoloLens 2: Innovation in reducing COVID-19 transmission and PPE usage.

BACKGROUND: The COVID-19 pandemic necessitated changes to the traditional medical ward round to protect staff and patients. This study investigated the value and acceptability of using the Microsoft HoloLens 2 mixed reality headset in a COVID-19 renal medicine ward. METHODS: The HoloLens 2 was used during the height of the COVID-19 pandemic and it was compared with the days prior to its introduction. Staff exposure to COVID-19 and PPE usage were measured, and staff and patients were surveyed on the HoloLens 2 experience. RESULTS: The average ward round was significantly shorter with the use of the HoloLens 2 (94 minutes vs 137 minutes; p=0.006). With the HoloLens 2, only the consultant was in direct contact with COVID-19 patients compared with up to seven staff members on a normal ward round. Personal protective equipment usage was reduced by over 50%. Both staff and patients were positive about its use but raised some important concerns. CONCLUSION: The HoloLens 2 mixed reality technology is an innovative solution to the challenges posed by COVID-19 to the traditional medical ward round.