Modified Radiation Lobectomy Strategy of Radioembolization for Right-Sided Unresectable Primary Liver Tumors.

PURPOSE: To assess the safety and effectiveness of using modified radiation lobectomy (mRL) to treat primary hepatic tumors located in the right hepatic lobe (Segments V-VIII) and to determine future liver remnant (FLR) hypertrophy. MATERIALS AND METHODS: A retrospective review was performed at a single institution to include 19 consecutive patients (7 females, 12 males) who underwent single-session mRL for right-sided primary hepatic tumors: 15 received segmentectomy plus lobectomy (segmental dose of >190 Gy and lobar dose of >80 Gy); 4 were treated with the double-segmental approach (dominant segments of >190 Gy and nondominant segments of >80 Gy). Treated tumors included 13 hepatocellular carcinoma (HCC), 4 cholangiocarcinoma (CCA), and 2 mixed-type HCC-CCA with a median dominant tumor size of 5.3 cm (interquartile range [IQR], 3.7-7.3 cm). FLR of the left hepatic lobe was measured at baseline, T1 (4-8 weeks), T2 (2-4 months), T3 (4-6 months), and T4 (9-12 months). RESULTS: Objective tumor response and tumor control were achieved in 17 of the 19 (89.5%) and 18 of the 19 (94.7%) patients, respectively. FLR hypertrophy was observed at T1 (median, 47.8%; P = .025), T2 (median, 48.4%; P = .012), T3 (median, 50.4%; P = .015), and T4 (median, 59.1%; P < .001). Patients without cirrhosis demonstrated greater hypertrophy by 6 months (median, 55.8% vs 47.2%; P = .031). One patient developed a Grade 3 adverse event (ascites requiring paracentesis) at 1-month follow-up. Grade ≥2 serum toxicities were associated with worse baseline Child-Pugh Score, serum albumin, and total bilirubin (P < .05). Among 7 patients who underwent neoadjuvant mRL, 2 underwent resection and 1 received liver transplant. CONCLUSIONS: mRL appears safe and effective for treatment of right-sided primary hepatic tumors with the benefit of promoting FLR hypertrophy.

Tumor Size and Watershed Area Correlate with Incomplete Treatment and Tumor Progression after Selective Radioembolization for Hepatocellular Carcinoma.

PURPOSE: To identify factors of incomplete treatment after segmental transarterial radioembolization (TARE) for treatment-naive and solitary hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 75 consecutive patients (age, 68.5 years [SD ± 8.0]; 25/75 [33.3%] women) with treatment-naive, solitary HCC underwent segmental or subsegmental TARE with glass microspheres (tumor size, 3.8 cm [SD ± 2.2]; administered dose, 222.6 Gy [SD ± 123.9]) at a single institution from November 2015 to June 2022. Radiologic response and progression-free survival (PFS) were assessed as per modified Response Evaluation Criteria in Solid Tumors. RESULTS: Complete treatment was achieved in 48 of 75 (64.0%) patients (mean follow-up, 33.2 months [SD ± 27.4]). Patients with incomplete treatment (27/75, 36%) presented with larger tumor size (5.0 [SD ± 2.5] vs 3.1 [SD ± 1.6] cm; P = .0001), with more tumors located in the watershed zone (81.5% vs 41.7%; P = .001). These patients were less likely to be bridged to transplant or resection (22.2% vs 52.1%; P = .015). Watershed tumors demonstrated worse target tumor PFS (median PFS, 19 months vs not reached; P = .0104) and overall PFS (9.1 months vs not reached; P = .0077). Watershed location was associated with worse PFS among tumors >3 cm in size (8.4 months vs not reached; P = .035) but not in tumors ≤3 cm in size (52.2 months vs not reached; P = .915). CONCLUSIONS: Tumor size and watershed location were associated with incomplete treatment after segmental TARE for HCC. Watershed tumors were associated with worse PFS, particularly tumors larger than 3 cm. These tumors may require careful treatment planning and repeated treatments to ensure a durable response.

Selective internal radiation therapy using yttrium-90 microspheres for treatment of localized and locally advanced intrahepatic cholangiocarcinoma.

OBJECTIVES: To evaluate safety and effectiveness of selective internal radiation therapy (SIRT) using yttrium-90 for localized and locally advanced intrahepatic cholangiocarcinoma (iCCA). METHODS: A retrospective review was performed of patients with localized iCCA treated with SIRT at a single institution. Overall survival (OS), local tumor response, progression-free survival (PFS), and toxicity were collected. Stratified analysis was performed based on surgical resection. Predictor analysis of OS was performed using the Fine-Grey regression analysis model with patients bridged to surgery regarded as competing events. RESULTS: A total of 28 consecutive patients with localized iCCA were treated with a total of 38 sessions of SIRT (17 segmental, 13 lobar, and 8 combined deliveries) and a mean dominant target dose per session of 238.4 ± 130.0 Gy. The cumulative radiologic response rate was 16/28 (57.1%) with a median PFS of 265 days. Median survival time (MST) was 22.9 months for the entire cohort with 1-year and 3-year survival of 78.4% and 45.1%, respectively. Ten patients (34.5%) were downstaged to surgical intervention (7 resection, 3 transplant) and showed longer OS (p = 0.027). The 1-year and 3-year OS for patients who received surgery were 100% and 62.5% (95% CI: 14.2-89.3%), respectively. Age (p = 0.028), Eastern Cooperative Oncology Group performance status (p = 0.030), and objective radiologic response (p=0.014) are associated with OS. Two ≥grade 3 hyperbilirubinemia, anemia, and one pleuro-biliary fistula occurred post-SIRT. CONCLUSIONS: SIRT for localized iCCA is safe and effective in achieving radiological response, downstaging to surgery and transplant, and resulting in pathologic necrosis. CLINICAL RELEVANCE STATEMENT: Selective internal radiation therapy should be considered for patients with localized and locally advanced intrahepatic cholangiocarcinoma. KEY POINTS: • The effectiveness of radioembolization for intrahepatic cholangiocarcinoma (iCCA) can be underestimated given the inclusion of extrahepatic disease. • Radioembolization is safe and effective for local and locally advanced iCCA. Age, Eastern Cooperative Oncology Group performance status, and radiologic response are associated with survival. • Radioembolization should be considered for patients with localized and locally advanced iCCA.

Relationship between BMI and prognosis of chronic heart failure outpatients in Vietnam: a single-center study.

Background: Insufficient data exists regarding the relationship between body mass index (BMI) and the prognosis of chronic heart failure (CHF) specifically within low- and middle-income Asian countries. The objective of this study was to evaluate the impact of BMI on adverse outcomes of ambulatory patients with CHF in Vietnam. Methods: Between 2018 and 2020, we prospectively enrolled consecutive outpatients with clinically stable CHF in an observational cohort, single-center study. The participants were stratified according to Asian-specific BMI thresholds. The relationships between BMI and adverse outcomes (all-cause death and all-cause hospitalization) were analyzed by Kaplan-Meier survival curves and Cox proportional-hazards model. Results: Among 320 participants (age 63.5 ± 13.3 years, 57.9% male), the median BMI was 21.4 kg/m2 (IQR 19.5-23.6), and 10.9% were underweight (BMI <18.50 kg/m2). Over a median follow-up time of 32 months, the cumulative incidence of all-cause mortality and hospitalization were 5.6% and 19.1%, respectively. After multivariable adjustment, underweight patients had a significantly higher risk of all-cause mortality than patients with normal BMI (adjusted hazard ratios = 3.03 [95% CI: 1.07-8.55]). Lower BMI remained significantly associated with a worse prognosis when analyzed as a continuous variable (adjusted hazard ratios = 1.27 [95% CI: 1.03-1.55] per 1 kg/m2 decrease for all-cause mortality). However, BMI was not found to be significantly associated with the risk of all-cause hospitalization (p > 0.05). Conclusion: In ambulatory patients with CHF in Vietnam, lower BMI, especially underweight status (BMI < 18.5 kg/m2), was associated with a higher risk of all-cause mortality. These findings suggest that BMI should be considered for use in risk classification, and underweight patients should be managed by a team consisting of cardiologists, nutritionists, and geriatricians.

Aicardi Syndrome Is a Genetically Heterogeneous Disorder.

Aicardi Syndrome (AIC) is a rare neurodevelopmental disorder recognized by the classical triad of agenesis of the corpus callosum, chorioretinal lacunae and infantile epileptic spasms syndrome. The diagnostic criteria of AIC were revised in 2005 to include additional phenotypes that are frequently observed in this patient group. AIC has been traditionally considered as X-linked and male lethal because it almost exclusively affects females. Despite numerous genetic and genomic investigations on AIC, a unifying X-linked cause has not been identified. Here, we performed exome and genome sequencing of 10 females with AIC or suspected AIC based on current criteria. We identified a unique de novo variant, each in different genes: KMT2B, SLF1, SMARCB1, SZT2 and WNT8B, in five of these females. Notably, genomic analyses of coding and non-coding single nucleotide variants, short tandem repeats and structural variation highlighted a distinct lack of X-linked candidate genes. We assessed the likely pathogenicity of our candidate autosomal variants using the TOPflash assay for WNT8B and morpholino knockdown in zebrafish (Danio rerio) embryos for other candidates. We show expression of Wnt8b and Slf1 are restricted to clinically relevant cortical tissues during mouse development. Our findings suggest that AIC is genetically heterogeneous with implicated genes converging on molecular pathways central to cortical development.

Segmental Yttrium-90 Radioembolization Using Glass Microspheres Greater than 400 Gray for the Treatment of Intrahepatic Cholangiocarcinoma: A Preliminary Experience.

Radiation segmentectomy with a dose of >190 Gy using yttrium-90 (90Y) glass microspheres for intrahepatic cholangiocarcinoma (iCCA) has been shown to be safe and effective. The present study further increased the dose to >400 Gy for treatment of iCCA as complete pathologic necrosis has been shown in hepatocellular carcinoma using this ablative approach. A total of 10 patients with 13 tumors (median size, 5.3 cm; range, 1.5-13.6 cm) at a single institution underwent >400-Gy segmental radioembolization. Objective response was achieved in all tumors (13 of 13, 100%). One patient developed a Grade 3 or greater major adverse event (stroke and hepatic decompensation). One patient was bridged to transplant (>95% pathologic necrosis), whereas another underwent resection (>99% necrosis). Contralateral hypertrophy was observed in 6 out of 6 patients treated with modified lobectomy dosing, with a functional liver reserve increase from a median of 31.5% to 57.1%. The present report suggests that segmental transarterial radioembolization with >400 Gy is feasible in terms of safety and effectiveness for treating iCCA.

Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in RUNX1, GATA2, and DDX41.

Individuals with germ line variants associated with hereditary hematopoietic malignancies (HHMs) have a highly variable risk for leukemogenesis. Gaps in our understanding of premalignant states in HHMs have hampered efforts to design effective clinical surveillance programs, provide personalized preemptive treatments, and inform appropriate counseling for patients. We used the largest known comparative international cohort of germline RUNX1, GATA2, or DDX41 variant carriers without and with hematopoietic malignancies (HMs) to identify patterns of genetic drivers that are unique to each HHM syndrome before and after leukemogenesis. These patterns included striking heterogeneity in rates of early-onset clonal hematopoiesis (CH), with a high prevalence of CH in RUNX1 and GATA2 variant carriers who did not have malignancies (carriers-without HM). We observed a paucity of CH in DDX41 carriers-without HM. In RUNX1 carriers-without HM with CH, we detected variants in TET2, PHF6, and, most frequently, BCOR. These genes were recurrently mutated in RUNX1-driven malignancies, suggesting CH is a direct precursor to malignancy in RUNX1-driven HHMs. Leukemogenesis in RUNX1 and DDX41 carriers was often driven by second hits in RUNX1 and DDX41, respectively. This study may inform the development of HHM-specific clinical trials and gene-specific approaches to clinical monitoring. For example, trials investigating the potential benefits of monitoring DDX41 carriers-without HM for low-frequency second hits in DDX41 may now be beneficial. Similarly, trials monitoring carriers-without HM with RUNX1 germ line variants for the acquisition of somatic variants in BCOR, PHF6, and TET2 and second hits in RUNX1 are warranted.

Integrated multi-omics for rapid rare disease diagnosis on a national scale.

Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). This included major impacts, such as informing precision treatments, surgical and transplant decisions and palliation, in 94 patients (60%). Our results provide preliminary evidence of the clinical utility of integrating multi-omic approaches into mainstream diagnostic practice to fully realize the potential of rare disease genomic testing in a timely manner.

Expanding the phenotype of DNMT3A as a cause a congenital myopathy with rhabdomyolysis.

Pathogenic variants in DNMT3A are most commonly associated with Tatton-Brown-Rahman Syndrome (TBRS), but includes other phenotypes such as Heyn-Sproul-Jackson syndrome and acute myeloid leukemia (AML). We describe a patient presenting to the neuromuscular clinic with a de novo missense variant in DNMT3A where the striking clinical feature is that of a congenital myopathy with associated episodes of rhabdomyolysis, severe myalgias and chest pain along with phenotypic features associated with TBRS. Muscle biopsy showed minor myopathic features and cardiac investigations revealed mildly impaired bi-ventricular systolic function. We confirmed the DNA methylation profile matched haplo-insufficient TBRS cases, consistent with a loss of methyltransferase activity. Our report emphasizes the phenotypic overlap of patients with syndromic disorders presenting to neuromuscular clinics and limitations of gene panels in establishing a molecular diagnosis.

Al-Gazali Skeletal Dysplasia Constitutes the Lethal End of ADAMTSL2-Related Disorders.

Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death.

Pregnancy loss and perinatal death are devastating events for families. We assessed 'genomic autopsy' as an adjunct to standard autopsy for 200 families who had experienced fetal or newborn death, providing a definitive or candidate genetic diagnosis in 105 families. Our cohort provides evidence of severe atypical in utero presentations of known genetic disorders and identifies novel phenotypes and disease genes. Inheritance of 42% of definitive diagnoses were either autosomal recessive (30.8%), X-linked recessive (3.8%) or autosomal dominant (excluding de novos, 7.7%), with risk of recurrence in future pregnancies. We report that at least ten families (5%) used their diagnosis for preimplantation (5) or prenatal diagnosis (5) of 12 pregnancies. We emphasize the clinical importance of genomic investigations of pregnancy loss and perinatal death, with short turnaround times for diagnostic reporting and followed by systematic research follow-up investigations. This approach has the potential to enable accurate counseling for future pregnancies.

Endovascular thrombectomy and repair of suprarenal inferior vena cava thrombosis: A case series.

OBJECTIVES: The objective of this study is to document the combined use of catheter-based thrombectomy/thrombolysis with endovascular repair of high-risk segments of the inferior vena cava in the setting of iatrogenic and traumatic injuries. While the use of endovascular techniques to treat caval thrombosis is well documented and often preferred due to its minimally invasive nature, there is still little literature that focuses on the nuances related to injury of high mortality areas of the IVC as a result of major trauma, transplant, and other surgical interventions. METHODS: An IRB-approved retrospective review of all patients undergoing IVC thrombectomy was performed at a single tertiary care academic center between January 2018 and July 2021. Cases were subsequently selected based on those who underwent primary mechanical thrombectomy followed by endovascular stenting (or angioplasty). Among this cohort, four patients who underwent this procedure in the context of iatrogenic and traumatic injuries were included. RESULTS: All four patients undergoing primary mechanical thrombectomy followed by endovascular stenting (or angioplasty) due to IVC thrombus and/or stenosis were technically successful with immediate positive clinical outcomes. CONCLUSIONS: Mechanical thrombectomy in conjunction with IVC recanalization via stenting may be a useful intervention with promising technical success and positive clinical outcomes for occlusive thrombosis and IVC stenosis.

Combination of transarterial radioembolization with atezolizumab and bevacizumab for intermediate and advanced staged hepatocellular carcinoma: A preliminary report of safety and feasibility.

Purpose: The IMbrave150 Phase III trial demonstrated the superiority of atezolizumab and bevacizumab (Atezo/Bev) over sorafenib for unresectable hepatocellular carcinoma (HCC). The present study aims to evaluate the feasibility of TARE in combination with Atezo/Bev for the treatment of intermediate and advanced staged HCC. Methods: A retrospective review at a single institution was performed between May 2021 and December 2022. Patients who received TARE using yttrium-90 (Y90) with concomitant or sequential Atezo/Bev systemic treatment were included. The following outcomes were retrieved: overall survival (OS), radiologic tumor response, progression-free survival, technical adverse events related to TARE, and toxicity based on the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Results: Ten consecutive patients with intermediate (n â€‹= â€‹4) and advanced stage HCC (n â€‹= â€‹6) were treated with TARE and sequential/concomitant Atezo/Bev. Tumor control was achieved in all TARE-treated target lesions (100%). Overall disease progression occurred in 4 patients with PFS of 78.8% and 66.7% at 6- and 12- months, respectively. Two patients died at follow-up, with 6-month and 12-month OS rates of 90.0% and 77.1%, respectively. Three (75%) patients with intermediate stage disease were downstaged into Milan criteria. One patient developed grade 3 transaminitis and hypoglobulinemia, while Atezo/Bev was switched to Lenvatinib in another patient due to immunotherapy related myositis. Conclusion: This study demonstrates the initial safety and feasibility of combined TARE with Atezo/Bev for intermediate/advanced stage HCC. Further prospective studies with larger sample sizes are warranted.

Transarterial Radioembolization versus Transarterial Chemoembolization Plus Percutaneous Ablation for Unresectable, Solitary Hepatocellular Carcinoma of ≥3 cm: A Propensity Score-Matched Study.

PURPOSE: To compare the safety and effectiveness of transarterial radioembolization (TARE) and transarterial chemoembolization with drug-eluting embolic agents combined with percutaneous ablation (transarterial chemoembolization [TACE] + ablation) in the treatment of treatment-naïve, unresectable, solitary hepatocellular carcinoma (HCC) of ≥3 cm. MATERIALS AND METHODS: Twenty-nine patients with treatment-naïve, unresectable, solitary HCC of ≥3 cm received combined TACE + ablation, and 40 patients received TARE at a single institution. Local tumor response, tumor progression-free survival (PFS), overall survival, need for reintervention, bridge to transplant, and major complications were compared. Clinical variables and outcomes were compared before and after propensity score matching (PSM). RESULTS: Before PSM, patients who underwent TARE had a larger tumor size (3.7 vs 5.5 cm; P = .0005) and were older (61.5 vs 69.3 years; P = .0014). After PSM, there was no difference in baseline characteristics between the 2 groups, with the mean tumor sizes measuring 3.9 and 4.1 cm in the TACE + ablation and TARE cohorts, respectively. After PSM (n = 19 in each group), no statistically significant difference was observed in local radiological response (disease control rates, 100% vs 94.7%; P = .31), survival (subdistribution hazard ratio [SHR], 0.71; 95% confidence interval [CI], 0.28-1.80; P = .469), PFS (SHR, 0.61; 95% CI, 0.21-1.71; P = .342), bridge to transplant (21.1% vs 31.6%, P = .46), and major adverse event rates (15.8% vs 10.5%, P = .63) between the 2 groups. The mean total number of locoregional interventions was higher in the TACE + ablation cohort (1.9 vs 1.3 sessions, P = .02), with an earlier median reintervention trend (SHR, 0.61; 95% CI, 0.20-1.32; P = .167). CONCLUSIONS: The present study showed that TARE and the combination of TACE and ablation are comparable in safety and effectiveness for treating treatment-naïve, unresectable, solitary HCC of ≥3 cm.

Variable expressivity in a four-generation ACDMPV family with a non-coding hypermorphic SNV in trans to the frameshifting FOXF1 variant.

Heterozygous single nucleotide variants (SNVs) or copy-number variant deletions involving FOXF1 or its distant lung-specific enhancer on chromosome 16q24.1 have been identified in 80-90% of patients with Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe a four-generation family with a deceased ACDMPV neonate, her sibling from the electively terminated pregnancy, healthy mother with a history of pulmonary arterial hypertension (PAH), an unaffected aunt, an aunt deceased due to findings consistent with ACDMPV, and a reportedly unaffected grandmother, all with the frameshifting variant c.881_902dup (p.Gly302Profs*46) in FOXF1, and a deceased great-grandmother with a history of PAH. Genome sequencing analyses in the proband's unaffected mother revealed a non-coding putative regulatory SNV rs560517434-A within the lung-specific distant FOXF1 enhancer in trans to the FOXF1 frameshift mutation. Functional testing of this variant using an in vitro luciferase reporter assay showed that it increased FOXF1 promoter activity 10-fold. Our studies further demonstrate that non-coding SNVs in the FOXF1 enhancer region can rescue the lethal ACDMPV phenotype and support the compound inheritance gene dosage model.

The clinical and genetic features of hereditary pancreatitis in South Australia.

OBJECTIVE: To characterise the clinical phenotypes and genetic variants of hereditary pancreatitis in people diagnosed in South Australia. DESIGN, SETTING, PARTICIPANTS: Cross-sectional study of people who received molecular diagnoses of hereditary pancreatitis from one of four major diagnostic services in South Australia, 1 January 2006 - 30 June 2021. MAIN OUTCOME MEASURES: Genotypic and clinical features of people with hereditary pancreatitis, including age at onset, attack frequency, pain indices, use of opioid medications, and physical and mental health impact of hereditary pancreatitis. RESULTS: We identified 44 people from ten families who received molecular diagnoses of hereditary pancreatitis during 2006-21 (including 25 Indigenous people [57%] and 27 women [61%]): 36 with PRSS1, five with SPINK1, and three with PRSS1 and SPINK1 mutations (determined by whole exome sequencing). Symptom onset before the age of ten years was reported by 37 people (84%). Pancreatitis-related pain during the preceding four weeks was described as moderate or high by 35 people (79%); 38 people regularly used opioids (86%). Fifteen patients had diabetes mellitus (34%), and eight had undergone pancreatic surgery (18%). The estimated prevalence of hereditary pancreatitis was 1.1 (95% CI, 0.72-1.4) cases per 100 000 population for non-Indigenous and 71 (95% CI, 66-77) cases per 100 000 population for Indigenous South Australians. Among people with adult-onset chronic pancreatitis admitted to South Australian public hospitals during 2001-2019, the proportions of Indigenous people (12%) and women (38%) were smaller than we report for hereditary pancreatitis. CONCLUSION: The estimated prevalence of hereditary pancreatitis in South Australia is higher than in Europe. PRSS1 gene mutations are important causes, particularly among Indigenous young people.

Green biorefinery: Microalgae-bacteria microbiome on tolerance investigations in plants.

Co-culture of microalgae and microorganisms, supported with the resulting synergistic effects, can be used for wastewater treatment, biomass production, agricultural applications and etc. Therefore, this study aimed to explore the role of Bacillus subtilis (B. subtilis) in tolerance against the harsh environment of seafood wastewater, at which these microalgal-bacterial flocs were formed by microalgae cultivation. In this present study, B. subtilis isolated from the cultivation medium of Chlorella vulgaris and exposed to different salinity (0.1-4% w/v sodium chloride) and various pH range to determine the tolerant ability and biofilm formation. Interestingly, this bacteria strain that isolated from microalgae cultivation medium showed the intense viability in the salt concentration exceeding up to 4% (w/v) NaCl but demonstrated the decrease in cell division as environmental culture undergoing over pH 10. Cell viability was recorded higher than 71% and 92% for B. subtilis inoculum in media with salt concentration greater than 20 gL-1 and external pH 6.5-9, respectively. This showed that B. subtilis isolated from microalgal-bacteria cocultivation exhibited its tolerant ability to survive in the extremely harsh conditions and thus, mitigating the stresses due to salinity and pH.