Bilateral adrenal hemorrhage in a postpartum woman with multiple thromboemboli: A case report.

BACKGROUND: Bilateral adrenal hemorrhage is a rare but often a fatal cause of primary adrenal insufficiency that can result in adrenal crisis if not identified and managed appropriately. CASE PRESENTATION: We present a case of a 27-year-old Caucasian female who was admitted to the hospital 17 days postpartum with pleuritic chest and flank pain, shortness of breath and nausea. Computed tomography imaging confirmed multiple thromboemboli including pulmonary emboli and noted bilateral bulky adrenal glands. She was managed for infection and pulmonary emboli; however, she complained of persistent headaches, nausea, and vomiting despite appropriate management. Radiology re-review found the computed tomography imaging was consistent with bilateral adrenal hemorrhage in hindsight. Subsequent endocrine evaluation with hypothalamic-pituitary-adrenal axis interrogation and adrenocorticotropic hormone (Synacthen) stimulation testing confirmed resultant primary adrenal insufficiency. She required urgent intravenous hydrocortisone and was subsequently discharged on oral adrenal replacement therapy and anticoagulation. CONCLUSIONS: Delay in identification and treatment of adrenal insufficiency can lead to catastrophic outcomes. This case highlights the challenge of diagnosing bilateral adrenal hemorrhage and resultant adrenal insufficiency as patients may not present with the classic risk factors, signs, symptoms, and electrolyte derangements.

Initial Trans-Arterial Chemo-Embolisation (TACE) Is Associated with Similar Survival Outcomes as Compared to Upfront Percutaneous Ablation Allowing for Follow-Up Treatment in Those with Single Hepatocellular Carcinoma (HCC) ≤ 3 cm: Results of a Real-World Propensity-Matched Multi-Centre Australian Cohort Study.

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC.

Fitz-Hugh-Curtis syndrome with disseminated intra-abdominal gonorrhoea.

Neisseria gonorrhoea continues to be implicated in a large proportion of sexually transmitted infections worldwide. Prompt recognition of infection is required to prevent further complications which include pelvic inflammatory disease and less commonly, perihepatitis which is known eponymously as Fitz-Hugh-Curtis syndrome. Third generation cephalosporins such as ceftriaxone remain effective in the treatment of gonococcal infection, however failure in initiation of appropriate antibiotic therapy in a timely manner can result in further disseminated disease. We describe an atypical case of Fitz-Hugh-Curtis syndrome presenting with multiple intra-abdominal gonococcal collections. Our case highlights the importance of a detailed sexual history in the evaluation of acute abdominal pain in at-risk patient demographics.

Different Patterns of Care and Survival Outcomes in Transplant-Centre Managed Patients with Early-Stage HCC: Real-World Data from an Australian Multi-Centre Cohort Study.

The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less (p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia.

Candida parapsilosis bone marrow infection in an immunocompetent patient.

Background: We discuss a case of an immunocompetent patient who presented with fever and tachypnoea, found to have Candida parapsilosis bone marrow infection, cultured on bone marrow aspirate sample. Candida parapsilosis is an opportunistic yeast pathogen that typically affects immunocompromised individuals, or occurs in patients with apparent introduced source; neither of these factors were present for this case. Bone marrow aspirates and trephines are not regular investigations for fever; however they can be useful diagnostic aids as evidenced in this case. Case report: An 83-year-old woman presenting with fevers and tachypnoea was being treated for a systemic bacterial infection, however was unresponsive to empirical antibiotic therapy. To exclude an occult malignancy, an 18-fluorodeoxyglucose positron emission tomography scan was conducted. Significant bone marrow uptake was noted, prompting a bone marrow aspirate and trephine to investigate for a hematological malignancy. While the trephine biopsy was benign, a culture of the aspirate grew Candida parapsilosis. Intravenous antifungal therapy was initiated; however, the patient did not improve despite targeted therapy likely due to delays in diagnosis, and was palliated. Conclusion: Our case seeks to demonstrate a novel case whereby a bone marrow aspirate culture provided a conclusive diagnosis of invasive Candida parapsilosis bone marrow infection, and guided treatment in an immunocompetent patient. It is important for clinicians to consider invasive fungal infections in febrile patients regardless of immune status. Additionally, when performing a bone marrow aspirate and trephine on a febrile patient, we recommend including aspirate fungal cultures to investigate for an invasive fungal infection.

Severe Hepatitis Complicating Olmesartan Enteropathy: A Case Report.

Introduction: Olmesartan, an angiotensin II receptor antagonist, is associated with an uncommon complication of enteropathy that presents insidiously, usually months to years after initial commencement of anti-hypertensive therapy which can be dose-dependent. It has a variable spectrum of clinical presentation but commonly presents as a moderate to severe malabsorptive process with potential severe complications related to poor end-organ perfusion. Lymphocytic gastritis and microscopic colitis are often noted in patients presenting with olmesartan-induced enteropathy; however, hepatic involvement has been less frequently observed. Case Presentation: We illustrate a case of a 43-year-old female presenting with 2 weeks of profuse non-bloody diarrhea in the context of olmesartan enteropathy which was complicated by an acute severe ischemic and enteropathic hepatopathy. Conclusion: Our case prompts clinicians to maintain a high index of suspicion in cases presenting with a seronegative enteropathy and concurrent acute liver injury while on olmesartan therapy. Cessation of olmesartan therapy resulted in prompt resolution of diarrheal symptoms and normalization of the acute transaminitis on subsequent three-week follow-up.

Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study.

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients.

Severe Adult Rotavirus Gastroenteritis: A Rare Case with Multi-Organ Failure and Critical Management.

BACKGROUND Infectious diarrheal illnesses such as rotavirus gastroenteritis are significant contributors to childhood morbidity and mortality, especially in low socio-demographic index regions. Major advances in addressing this issue include sanitation and clean water initiatives, as well as rotavirus immunization. In Australia, a robust vaccination program has significantly reduced childhood rotavirus infections, leading to decreased hospitalizations and mortality. However, cases of adult rotavirus still occur, and although these adult patients usually do not require interventional management, it is possible for them to present critically unwell and require resuscitation. CASE REPORT A previously well 65-year-old man presented to the Emergency Department febrile and hypotensive with severe diarrhea attributed to rotavirus. Clinically, he presented with mixed hypovolemic and septic shock. Despite initial resuscitation, he had multiple severe acute end-organ complications, secondary to poor perfusion. He acquired an acute kidney injury, type-2 myocardial infarction, and ischemic hepatic injury. The mainstay of management was rapid fluid resuscitation, continuous renal replacement therapy, and monitoring in the Intensive Care Unit; however, it was crucial to empirically treat for other causes of shock. CONCLUSIONS To the best of our knowledge, there is a scarcity of reports documenting the management of severe rotavirus gastroenteritis in adults. We recommend advising elderly patients to avoid contact with individuals with diarrheal illnesses, especially rotavirus gastroenteritis. Clinicians should also promote awareness regarding the potential severity of a disease that is typically managed conservatively, and be aware that intervention can be required in severe gastroenteritis.

Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine: Three case reports.

BACKGROUND: Highly effective and well-tolerated direct-acting antiviral (DAA) therapies have revolutionised the management of hepatitis C virus (HCV); however, niche populations face treatment barriers. DAAs co-prescribed with several first-generation anti-epileptic drugs (AEDs) are contraindicated due to drug-drug interactions. A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir, glecaprevir and pibrentasvir due to potent cytochrome P450 (CYP) 3A4 induction. Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir's area under curve to infinite time. Sofosbuvir-velpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently, virological treatment failure. This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible, impractical or unacceptable. However, the properties of current generation DAA therapies, including high-potency non-structural protein 5A inhibitory effect, may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction. CASE SUMMARY: We present a case series of three patients with non-cirrhotic, treatment-naïve, genotype 1a, 1b, and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir, while co-prescribed carbamazepine for seizure disorders. Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants. DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration, and taken with meals to improve absorption. Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes. CONCLUSION: DAA therapies, including glecaprevir-pibrentasvir, warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine, particularly if AED substitution is not feasible.

Case of leptospirosis causing pancytopenia.

We present the case of a young female landscaper who presented to an Australian tertiary hospital with persistent fevers and new pancytopenia. Extensive initial workup for her presenting illness did not identify a cause; however, a detailed history of her occupation revealed she worked heavily with soil on farms that had domestic livestock in addition to rodents. Hence, further serological testing for leptospirosis was performed, revealing a diagnosis of infection with Leptospira interrogans serovar Hardjo. Treatment covering leptospirosis was commenced, and she improved clinically, and her cell counts returned to normal. Pancytopenia is a rare manifestation of leptospirosis and has only been reported in a handful of case studies. We highlight that leptospirosis should be considered as a differential diagnosis in those with fever, and new pancytopaenia, particularly in patients with relevant risk factors for exposure.

Prevalence and prognostic significance of vitamin C deficiency in patients with acute upper gastrointestinal bleeding: a prospective cohort study.

BACKGROUND: Vitamin C is an essential dietary nutrient important for collagen synthesis, including within the gastrointestinal tract. AIM: We aimed to document the prevalence of Vitamin C deficiency (VCD) in patients who present with upper gastrointestinal bleeding (UGIB) and its association with clinical outcomes. METHODS: We conducted a prospective cohort study of patients presenting with UGIB. Fasting Vitamin C levels were collected at admission. Primary outcomes were the prevalence of VCD (Vitamin C level <23 µmol/L, severe VCD < 12 µmol/L) and a composite outcome of adverse events, stratified by VCD status. Secondary outcomes were prolonged hospitalisation and the need for ICU admission. RESULTS: A total of 227 patients were included (mean age 64.5 years, males 63.9%). VCD was identified in 74 (32.6%) and severe deficiency in 32 (14.1%) patients. VCD was associated with a higher composite endpoint of AE (45.9% vs 24.8%, p < 0.01), higher in-hospital mortality (9.5% vs 1.3%, p < 0.01), increased prolonged admissions (62.2% versus 47.1%, p = 0.03) and increased rebleeding (17.6% vs 7.8%, p = 0.03), compared with patients with normal Vitamin C levels. Multivariate logistic regression models showed that VCD was independently associated with the composite endpoint of AE. CONCLUSION: VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding and length of stay. Interventional studies are required to determine the impact of early Vitamin C supplementation on clinical outcomes.

Assessing vitamin D as a biomarker in inflammatory bowel disease.

Background and Aim: A reliable serum biomarker for inflammatory bowel disease (IBD) activity is needed. Vitamin D is involved in inflammation and has been demonstrated to be low in IBD patients with active disease. It is routinely measured in IBD patients. Therefore, vitamin D may have a role as a serum biomarker in IBD. This study aims to investigate whether serum vitamin D may be useful as a biomarker in IBD in a real-world IBD population. Methods: Patients were identified by review of fecal calprotectin (FCP) results, and those who had a clinical review, vitamin D test, and FCP performed within 3 months were included. Clinical scores were calculated from chart review. Nonparametric tests were used to investigate vitamin D and FCP levels, serum biomarkers, and clinical scores. Results: Of 616 patients identified, 325 episodes of matched vitamin D level and biomarker data were obtained. A statistically significant correlation was found between vitamin D levels and FCP levels for all patients (r = -0.19 [s -0.29 to -0.080], P < 0.001]. This remained true when patients were divided into IBD subsets. Low vitamin D was associated with partial Mayo scores and C-reactive protein (CRP) to albumin ratio in ulcerative colitis, and CRP and CRP/albumin ratio in Crohn's disease. Conclusion: Vitamin D level is negatively correlated with FCP and it may be considered as an adjunct biomarker at this stage. A prospective study would be beneficial to investigate further correlations between vitamin D and existing biomarkers of inflammation in IBD.

Ischaemic stroke as the first presentation of antineutrophilic cytoplasmic autoantibody-associated vasculitis.

The diagnosis of antineutrophil cytoplasmic autoantibody-associated vasculitis in first-episode strokes is particularly challenging, especially in patients lacking features of systemic vasculitis. We present the case of a 71-year-old woman with positive myeloperoxidase antineutrophil cytoplasmic antibodies and negative proteinase 3 autoantibodies. The patient presented with 1 week history of pyramidal weakness in both upper and lower limbs, hyperreflexia, and clonus. Magnetic resonance imaging of the brain demonstrated widespread bihemispheric cortical and deep white matter acute infarcts, which are consistent with features of stroke secondary to vasculitis. Myeloperoxidase antineutrophilic cytoplasmic autoantibody-positive vasculitis diseases are more commonly associated with renal, pulmonary, and cutaneous manifestations; however, in our patient, the central nervous system features predominated. This case highlights the challenges of diagnosing primary central nervous system vasculitis, in this case, an atypical myeloperoxidase antineutrophilic cytoplasmic autoantibody-positive disease without the classical disease course and clinical signs.

Splenunculus mimicking splenomegaly in a patient with synchronous herpes simplex 1 viremia and myelosuppression.

Splenunculus, or congenital accessory spleen, is a benign anatomical variation, and is rarely of clinical consideration in routine clinical practice. We describe a patient who presented with synchronous herpes simplex 1 viraemia and myelosuppression, with a splenunculus mimicking splenomegaly, and we discuss the implications on clinical practice, investigations, and management.

An unusual case of multiple gastrointestinal stromal tumors in the small bowel presenting as occult and overt gastrointestinal bleeding.

We present a case report of a 59-year-old woman with multiple gastrointestinal stromal tumors as a cause of gastrointestinal bleeding. She initially presented with recurrent iron deficiency anemia and subsequent gastrointestinal bleeding over 10 years. An initial angiodysplastic lesion was identified, treated, and spot tattooed. Recurrent symptoms occurred leading to repeat investigations with a further subepithelial lesion with ulceration being identified. Computerized tomography enterography subsequently revealed an ileal intraluminal enhancing lesion, and she was referred to surgery. Surgical resection was ultimately performed, and multiple lesions were found to be present with histology revealing multiple gastrointestinal stromal tumors.

Altered peripheral factors affecting the absorption, distribution, metabolism, and excretion of oral medicines in Alzheimer's disease.

Alzheimer's disease (AD) has traditionally been considered solely a neurological condition. Therefore, numerous studies have been conducted to identify the existence of pathophysiological changes affecting the brain and the blood-brain barrier in individuals with AD. Such studies have provided invaluable insight into possible changes to the central nervous system exposure of drugs prescribed to individuals with AD. However, there is now increasing recognition that extra-neurological systems may also be affected in AD, such as the small intestine, liver, and kidneys. Examination of these peripheral pathophysiological changes is now a burgeoning area of scientific research, owing to the potential impact of these changes on the absorption, distribution, metabolism, and excretion (ADME) of drugs used for both AD and other concomitant conditions in this population. The purpose of this review is to identify and summarise available literature reporting alterations to key organs influencing the pharmacokinetics of drugs, with any changes to the small intestine, liver, kidney, and circulatory system on the ADME of drugs described. By assessing studies in both rodent models of AD and samples from humans with AD, this review highlights possible dosage adjustment requirements for both AD and non-AD drugs so as to ensure the achievement of optimum pharmacotherapy in individuals with AD.