An Unusual Case of Lethal Strongyloides stercoralis-Associated Chronic Fulminant Colitis in an Immunocompetent Patient.

A 70-year-old immunocompetent Lebanese male presented with 3-month history of watery diarrhoea and abdominal pain after recently arriving to Australia from Lebanon. He had a colectomy for an iatrogenic bowel perforation associated with a colonoscopy in Lebanon several months prior. His computed tomography (CT) scan demonstrated pancolitis. Stool culture and polymerase chain reaction (PCR) were positive for Strongyloides stercoralis. Despite Strongyloides treatment and total parenteral nutrition, his pancolitis unexpectedly persisted despite negative stool cultures, and the patient failed to progress over several weeks with worsening abdominal pain. A colectomy was considered. However, due to his recent myocardial infarct requiring cardiac stenting, his anticoagulant and antiplatelets could not be ceased for at least 3 months without significant cardiac risk. After hospitalisation for several weeks in Australia, he was discharged against medical advice and flew back to Lebanon, where he presented with worsening pain and underwent a subtotal colectomy. Unfortunately, he developed multiorgan failure and died 3 weeks following his colectomy. Strongyloides-related pancolitis is a rare condition in immunocompetent adults that has the potential to persist and be lethal, despite microbiological antiparasitic eradication.

Pathological and clinical outcomes following neoadjuvant dual HER2 therapy for early-stage breast cancer: An Australian institutional real-world experience.

AIM: There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non-metastatic HER2-positive breast cancer, which may be used in combination with conventional chemotherapy to optimise pathological responses at surgery. However, these therapies, particularly the chemotherapeutic components, may portend significant and long-lasting toxicity. Hence, de-escalation of treatment intensity has been an area of interest and was evaluated in the phase II NeoSphere study. Herein, we report the real-world pathological and survival outcomes from neoadjuvant taxane and dual HER2 blockade recorded at our centre. METHODS: This was a retrospective cohort study of patients receiving neoadjuvant pertuzumab, trastuzumab and taxane chemotherapy for non-metastatic HER2-positive breast cancer at a single centre in Sydney, Australia. We collected data pertaining to baseline demographic characteristics, pathological response rates, post-surgical prescribing patterns and also undertook survival analyses for invasive disease-free survival (iDFS) as well as exploratory analyses for correlations between pre-specified clinicopathologic factors and pathological response at surgery. RESULTS: Our population was largely similar at baseline to the NeoSphere study. 71 patients were included in the final analysis. 61% achieved a pathological complete response (pCR). Three patients received conventional chemotherapy in the adjuvant setting. 92% of included patients were alive and disease-free at 3 years of follow-up. Only 3 events of recurrence or death were recorded at a median follow-up of 32 months. No significant difference in iDFS was noted between patients achieving pCR and those with residual disease at surgery. CONCLUSION: This study demonstrates that de-escalated adjuvant treatment for HER2-positive early breast cancer achieved favourable pathological and long-term outcomes comparable to large trials, some utilising more intensive chemotherapeutic components.

Spontaneous pneumomediastinum and pneumopericardium in a young male with asthma.

INTRODUCTION: Spontaneous pneumomediastinum with pneumopericardium is an uncommon clinical entity. CASE STUDY: Here, we report the case of a 23-year-old male with asthma who presented with acute chest pain and shortness of breath after an episode of coughing and sneezing. CT scans of the chest and neck revealed pneumomediastinum and pneumopericardium with extensive subcutaneous emphysema extending into the axilla and neck. RESULTS: The patient was admitted for observation and analgesia. No other interventions were administered. Interval scans performed on day five of the admission demonstrated an interval reduction in the degree of air within the mediastinum, pericardium and subcutaneous tissues, and the patient was subsequently discharged home. CONCLUSION: This case outlines the presentation, diagnosis, and management of concurrent spontaneous pneumomediastinum and pneumopericardium.

Synthetic biology approaches for enhancing safety and specificity of CAR-T cell therapies for solid cancers.

CAR-T cell therapies have been successful in treating numerous hematologic malignancies as the T cell can be engineered to target a specific antigen associated with the disease. However, translating CAR-T cell therapies for solid cancers is proving more challenging due to the lack of truly tumor-associated antigens and the high risk of off-target toxicities. To combat this, numerous synthetic biology mechanisms are being incorporated to create safer and more specific CAR-T cells that can be spatiotemporally controlled with increased precision. Here, we seek to summarize and analyze the advancements for CAR-T cell therapies with respect to clinical implementation, from the perspective of synthetic biology and immunology. This review should serve as a resource for further investigation and growth within the field of personalized cellular therapies.

Conservative Treatment of an Unusual Presentation of Iliopsoas Phlegmon Related to Infected Intrauterine Contraceptive Device.

Iliopsoas phlegmon/abscess is uncommon, and individuals often present with nonspecific symptoms. Diagnosis is often delayed and almost always requires advanced imaging techniques such as computed tomography or magnetic resonance imaging. We report a case of a 51-year-old woman who presented with right lower limb swelling and associated rash with imaging demonstrating iliopsoas abscess secondary to an infected intrauterine contraceptive device. This rare case highlights the nonspecific presentation of iliopsoas abscess and the need to consider unusual sources of infection such as an intrauterine contraceptive device in women presenting with iliopsoas phlegmon and abscess.

Inactivation of Tulane virus and feline calicivirus by aqueous ozone.

Ongoing challenges with reproducible human norovirus cultivable assays necessitate the use of surrogates, such as feline calicivirus (FCV-F9) and Tulane virus (TV), during inactivation studies. Chlorine alternates used as control strategies include aqueous and gaseous ozone. This study aimed at determining the inactivation of FCV-F9 and TV by a portable ozone-generating device. FCV-F9 (∼8 log PFU/mL) or TV (∼6 log PFU/mL) in sterile-low-organic matter-containing-water was treated for 0-5 min, or in sterile-water containing newborn calf serum (high-organic matter/protein) for 0-38 min with ∼1 ppm ozone (pH 7-6). Infectivity was determined from triplicate treatments using plaque assays. FCV-F9 titers significantly decreased by 6.07 log PFU/mL after 5 min in ozonated low-organic-matter-containing-water and was non-detectable (≤2 log PFU/mL) after 36 min treatments in high-organic-matter-containing water (p < 0.05). TV titers decreased by 4.18 log PFU/mL after 4 min in ozonated low-organic-matter water (non-detectable after 4.5 min) and were non-detectable after 22.5 min treatments of high-organic-matter-containing water (p < 0.05). Overall, ∼1 ppm aqueous ozone significantly decreased FCV-F9 by >6 log PFU/mL after 5 min, TV to non-detectable levels (≤2 log PFU/mL) after 4.5 min and required longer treatments (>32 and >20 min, respectively) for ≥4 log reduction in high-organic-matter-containing water (p < 0.05). For ozone treatment of both viruses, the linear and Weibull models were similar for low-organic-load water, though the Weibull model was better for the high-organic load water. Prior filtration or organic load removal is recommended before ozonation for increased viral inactivation with decreased treatment-time.

Proteomics identifies the developmental regulation of HKDC1 in liver of pigs and mice.

During the perinatal period, unique metabolic adaptations support energetic requirements for rapid growth. To gain insight into perinatal adaptations, quantitative proteomics was performed comparing the livers of Yorkshire pigs at postnatal day 7 and adult. These data revealed differences in the metabolic control of liver function including significant changes in lipid and carbohydrate metabolic pathways. Newborn livers showed an enrichment of proteins in lipid catabolism and gluconeogenesis concomitant with elevated liver carnitine and acylcarnitines levels. Sugar kinases were some of the most dramatically differentially enriched proteins compared with neonatal and adult pigs including galactokinase 1 (Galk1), ketohexokinase (KHK), hexokinase 1 (HK1), and hexokinase 4 (GCK). Interestingly, hexokinase domain containing 1 (HKDC1), a newly identified fifth hexokinase associated with glucose disturbances in pregnant women, was highly enriched in the liver during the prenatal and perinatal periods and continuously declined throughout postnatal development in pigs and mice. These changes were confirmed via Western blot and mRNA expression. These data provide new insights into the developmental and metabolic adaptations in the liver during the transition from the perinatal period to adulthood in multiple mammalian species.

Clinical and cellular phenotypes resulting from a founder mutation in IL10RB.

Inborn errors of immunity are a group of rare genetically determined diseases that impair immune system development or function. Many of these diseases include immune dysregulation, autoimmunity or autoinflammation as prominent clinical features. In some children diagnosed with very early onset inflammatory bowel disease (VEOIBD), monogenic inborn errors of immune dysregulation underlie disease. We report a case of VEOIBD caused by a novel homozygous loss of function mutation in IL10RB. We use CyTOF with a broad panel of antibodies to interrogate the immunophenotype of this patient and detect reduced frequencies of CD4 and CD8 T cells with additional defects in some populations of T helper cells, innate-like T cells and memory B cells. Finally, we identify the patient's mutation as a founder allele in an isolated indigenous population and estimate the age of this variant by studying the shared ancestral haplotype.

Is preoperative hypoalbuminemia or hypoproteinemia a reliable marker for anastomotic leakage risk in patients undergoing elective colorectal surgery in an enhanced recovery after surgery (ERAS) program?

PURPOSE: Preoperative hypoalbuminemia has traditionally been used as a marker of nutritional status and is considered a significant risk factor for anastomotic leak (AL). METHODS: The Westmead Enhanced Recovery After Surgery (WERAS) prospectively collected database, consisting of 361 patients who underwent colorectal surgery with primary anastomosis, was interrogated. Preoperative serum albumin and protein levels (measured within 1 week of surgery) were plotted on receiver operating characteristic curves (ROC curves) and statistically analyzed for cutoff values, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). RESULTS: The incidence of AL was 4.4% (16/361). Overall mortality was 1.4% (5/361), 6.3% (1/16) in the AL group, and 1.2% (4/345) in the no AL group. The median preoperative albumin and protein level in the AL group were 39 g/L and 75 g/L, respectively. The median preoperative albumin and protein level in the no AL group were 38 g/L and 74 g/L, respectively. The Mann-Whitney U test showed no statistically significant difference in albumin levels (p = 0.4457) nor protein levels (p = 0.6245) in the AL and no AL groups. ROC curves demonstrated that preoperative albumin and protein levels were not good predictors of anastomotic leak. Cutoff values for albumin (38 g/L) and protein (75 g/L) both had poor PPV for AL (4.8% and 3.8% respectively). CONCLUSION: In patients undergoing elective colorectal surgery as part of an ERAS program, preoperative serum albumin and protein levels are not reliable in predicting AL. This may be because of nutritional supplementation provided as part of an ERAS program may correct nutritional deficits to protect against AL or that low albumin/protein is not as robust a marker of AL as previously reported.

Hermansky-Pudlak syndrome with early onset inflammatory bowel disease due to loss of dysbindin expression.

Hermansky-Pudlak syndrome (HPS) is a heterogeneous group of autosomal recessive genetic disorders characterized by oculocutaneous albinism, bleeding diathesis, and variable presentation of immune deficiency and dysregulation. The pathogenesis of HPS involves mutations in genes responsible for biogenesis and trafficking of lysosome-related organelles, essential for the function of melanosomes, platelet granules, and immune cell granules. Eleven genes coding for proteins in the BLOC-1, BLOC-2, BLOC-3 and AP-3 complexes have been implicated in the pathogenesis of HPS. To date, the rare subtype HPS-7 associated with bi-allelic mutations in DTNBP1 (dysbindin) has only been reported in 9 patients. We report a novel DTNBP1 splicing mutation in a 15-month-old patient with HPS-7 phenotype and severe inflammatory bowel disease (IBD). This patient's leukocytes have undetectable dysbindin protein. We also identify dysregulated expression of several genes involved in activation of the adaptive immune response. This case underscores the emerging immunological consequences of dysbindin deficiency and suggests that DTNBP1 mutations may underlie some rare cases of very early onset IBD.

PARC: Physics-aware recurrent convolutional neural networks to assimilate meso scale reactive mechanics of energetic materials.

The thermo-mechanical response of shock-initiated energetic materials (EMs) is highly influenced by their microstructures, presenting an opportunity to engineer EM microstructures in a "materials-by-design" framework. However, the current design practice is limited, as a large ensemble of simulations is required to construct the complex EM structure-property-performance linkages. We present the physics-aware recurrent convolutional (PARC) neural network, a deep learning algorithm capable of learning the mesoscale thermo-mechanics of EM from a modest number of high-resolution direct numerical simulations (DNS). Validation results demonstrated that PARC could predict the themo-mechanical response of shocked EMs with comparable accuracy to DNS but with notably less computation time. The physics-awareness of PARC enhances its modeling capabilities and generalizability, especially when challenged in unseen prediction scenarios. We also demonstrate that visualizing the artificial neurons at PARC can shed light on important aspects of EM thermos-mechanics and provide an additional lens for conceptualizing EM.

An unusual case of colonic duplication cyst in an adult with dysplasia.

Duplication cysts are rare benign congenital malformations typically identified in children by the age of 2 years. We report a rare case of colonic duplication cyst with dysplasia in an adult. A 32-year-old male was diagnosed with non-specific abdominal symptoms. Abdominopelvic computed tomography scan demonstrated a submucosal cystic lesion in the right colon. He underwent laparoscopic right hemicolectomy. Histopathology showed colonic duplication cyst with low grade dysplasia. He is due for a surveillance colonoscopy in 3 years. Duplication cyst in an adult colon with dysplasia is extremely rare. They are usually present in the terminal ileum. They have non-specific abdominal symptoms or can be asymptomatic. They are often identified incidentally or intraoperatively. Imaging may demonstrate a cystic lesion. Histopathology is required for definitive diagnosis. There are no guidelines or consensus on managing duplication cysts in adults. We recommend an oncological resection of the involved colon. Surveillance with routine colonoscopy is advisable.

Mini-Open Achilles Tendon Repair: Improving Outcomes While Decreasing Complications.

An acute rupture of the Achilles tendon is a traumatic injury that can cause considerable morbidity and reduced function. Nonoperative intervention may put patients at higher risk of rerupture, whereas surgical intervention carries risk of infection, wound complications, and iatrogenic nerve injury. The mini-open Achilles tendon repair technique has been popularized in helping decrease complications. The goal of this study was to examine and compare the functional outcomes and rate of complications in patients treated with a mini-open repair technique versus a traditional open repair for acute Achilles tendon ruptures. A retrospective review was performed of all patients with a complete Achilles tendon rupture that were treated by a single foot and ankle fellowship-trained surgeon. Functional outcome scores were assessed using the American Orthopaedic Foot and Ankle scoring system (AOFAS) and the Achilles Tendon Rupture Score (ATRS). Eighty-one patients with a complete Achilles tendon rupture underwent mini-open repair and 22 patients underwent traditional open repair surgery between 2013 and 2020. The mean follow-up was 38.40 months (range, 12-71). Mean preoperative AOFAS and ATRS improved in the mini-open group from 45.60 and 47.18 respectively, to 90.29 and 87.97 after surgery (p < .05). Mean preoperative AOFAS and ATRS scores for the traditional open repair (n = 22) cohort were 44.02 and 42.27, respectively. Postoperatively, the AOFAS and ATRS scores improved to 85.27 and 86.64 (P value < .05), respectively. There was no statistically significant difference in postoperative ATRS scores. However, the mini-open repair group showed a statistically higher postoperative AOFAS score (90.30) than the traditional open-repair group (85.27) (P value < .05). The overall complication rate for our study was 2.9% (2 mini-open repair and 1 traditional open repair). The complication rate in the mini-open repair group and traditional open repair cohort were 2.4% and 4.5%, respectively (P value > .05). One patient in the mini-open repair cohort (1.2%) reruptured his Achilles tendon 4 months postoperatively. A second patient in the mini-open repair group (1.2%) developed a superficial skin infection and suture irritation. One patient (4.5%) in the traditional open repair group developed a superficial skin infection. There were no sural nerve injuries in our series. The mini-open approach to repair a ruptured Achilles tendon is a viable treatment option to decrease the incidence rate of postoperative complications and rerupture rates while also producing a superior cosmetic result.Level of Evidence: 3 (retrospective cohort study N ≥ 30).

A comparative study of diagnostic accuracy in 3026 pleural biopsies and matched pleural effusion cytology with clinical correlation.

BACKGROUND: Pleural effusion can be caused by a wide range of benign and malignant conditions. Pleural biopsy and effusion cytology represent two key methods of pathological diagnosis. To compare the performance these two methods, a large cohort of matched pleural biopsy and effusion cytology with clinical follow-up was reviewed. METHODS: Pleural biopsies and effusion cytology specimens over a period of 18 years were retrieved. Cytology specimens collected within 7 days of pleural biopsy were matched. Reports were reviewed, and the cause for pleural effusion was determined by hospital disease coding and clinical data. RESULTS: Totally, 3026 cases were included. The leading cause of benign effusion was tuberculosis (n = 650). Malignant pleural effusion (MPE) was more common in older females (p < 0.001) and mostly due to lung cancer (n = 959), breast cancer (n = 64), and mesothelioma (n = 48). The inadequate/insufficient (B1/C1) rate of biopsy was higher than cytology (15.6% vs. 0.3%) but the rates for other diagnostic categories were similar. Biopsy and cytology showed a correlation coefficient of 0.315, improving to 0.449 when inadequate/insufficient (B1/C1) cases were excluded. The ROM for benign cytology (C2) was lower than biopsy (B2) (p < 0.001). Compared with biopsy, the diagnostic accuracy was higher in cytology overall and for metastatic carcinomas (p < 0.001) but lower for hematolymphoid malignancies (p = 0.014) and mesotheliomas (p = 0.002). CONCLUSIONS: These results suggest that effusion cytology may be better for confirming benignity and diagnosing carcinomatous MPE. In these cases, pleural biopsy may be withheld to reduce procedural risks. However, for suspected hematolymphoid malignancies and mesothelioma, biopsy should be considered.

Disparities in HIV Testing, Condom Use, and HIV Education Between Transgender and Not Transgender High School-Aged Youth: Findings From the 2019 Youth Risk Behavior Survey.

Transgender individuals are disproportionately affected by HIV in the United States. Given increased risk of HIV among youth, there is a need to understand HIV risk and protective factors among transgender individuals who are 18 years and younger. Patterns of HIV testing, HIV education, and condom use have known associations with HIV outcomes among youth in general, but are understudied among transgender youth. This study assessed these outcomes by developing a series of sex-stratified multivariable logistic regression models using pooled Youth Risk Behavior Survey data. Results indicate female and male transgender youth as well as males who were not sure they were transgender were more likely have tested for HIV compared with their not transgender peers. Male transgender youth were significantly less likely to have received HIV education compared with not transgender males. Females not sure if they were transgender and male transgender youth were significantly less likely to have used condoms compared with, respectively, not transgender female and not transgender male counterparts. In sum, condom use and HIV education both remain lower among transgender individuals relative to their not-transgender peers. This highlights the need for the promotion of culturally appropriate HIV education and HIV prevention supports among transgender youth.

Safe postoperative outcomes following early cholecystectomy for acute calculus cholecystitis regardless of symptom onset.

Objectives: There is growing evidence for reduced post-operative complications, and lower hospital costs associated with early cholecystectomy for acute calculus cholecystitis (AC) compared to delayed surgery. Limited high-quality evidence exists for how early, if at all, should surgeons be operating emergently for AC based on symptom onset. Material and Methods: Seven hundred seventy-four patients who had cholecystectomy performed by a single surgeon between January 2015-October 2022 were retrospectively reviewed. Five hundred fourty-one patients were analysed. Patients were divided into three groups based on symptom onset: Group 1: 0-72 hours (n= 305), Group 2: 72 hrs-1 week (n= 154) and Group 3: >1 week (n= 82). Results: Median operative time was most prolonged in Group 2 (96.5 minutes), and had the greatest proportion of reconstituting 95% cholecystectomies (n= 22/154, 14.29%) compared to Group 1 (p> 0.05). The conversion to open was between 0.65-1.64% in all groups. The greatest proportion of bile leak occurred in Group 1 (n= 7/305, 2.3%) followed by Group 3 (n= 1/82, 1.22%) (p> 0.05). All were successfully managed with ERCP and biliary stent. Median hospital stay was significantly prolonged in Group 2 (2.3 days) compared to Group 1 (2 days) (p= 0.03). The proportion of 95% cholecystectomies in Group 2 and 3 were not significant compared to Group 1. Conclusion: Early cholecystectomy for calculus cholecystitis, irrespective of the timing of symptoms appears to have safe postoperative outcomes. Surgeons do not necessarily need to limit early cholecystectomy for within 72 hours of symptom onset.