Primary Adnexal Signet-Ring Cell/Histiocytoid Carcinoma.

An 84-year-old man presented with a 2-year history of a progressive left-sided ptosis. Examination demonstrated a mechanical ptosis and concentric constriction of the palpebral aperture. CT imaging revealed demonstrated diffuse soft tissue infiltration of the upper and lower eyelids with extension into the anterior orbit. This case was diagnostically challenging because of a history of multiple other primary tumors. However, clinicoradiologic and histopathologic findings were consistent with a diagnosis of primary adnexal signet-ring cell/histiocytoid carcinoma. The patient underwent surgical excision but local recurrence was noted 2 months postoperatively.

Visual outcomes and patient satisfaction 1 and 12 months after combined implantation of extended depth of focus and trifocal intraocular lenses.

PURPOSE: To assess the 1-month and 12-month postoperative visual performance and subjective outcomes following combined implantation of an extended depth of focus (EDOF) intraocular lens (IOL) and a trifocal IOL. METHODS: The study enrolled consecutive patients undergoing refractive lens extraction or cataract surgery with combined implantation of an EDOF IOL (dominant eye) and trifocal IOL. Uncorrected (UDVA) and best-corrected (CDVA) distance visual acuities, uncorrected intermediate (UIVA) and near (UNVA) visual acuities, and subjective questionnaires were evaluated 1 month and 12 months postoperatively. RESULTS: The study enrolled 58 consecutive patients. Binocular UDVA, UIVA and UNVA were - 0.08 ± 0.07 logMAR, 0.15 ± 0.14 logMAR and 0.17 ± 0.11 logMAR at 1 month, compared to - 0.09 ± 0.06 logMAR (P = .323), 0.11 ± 0.10 logMAR (P = .030) and 0.13 ± 0.10 logMAR (P = 0.008) at 12 months. Satisfaction was high with 93.1% of patients fulfilled or more than fulfilled postoperatively, and 84.5% and 86.3% reported spectacle independence for near at the respective postoperative assessments. The mean daytime and nighttime quality of vision (QoV) scores were 9.12 ± 0.94 and 7.88 ± 1.74 at 1 month, compared to 9.24 ± 0.78 (P = .183) and 8.26 ± 1.38 (P = .043) at 12 months. CONCLUSIONS: This IOL combination provides good unaided visual acuity at 1 and 12 months postoperatively, with high functional vision and postoperative satisfaction reported at 1 and 12 months. However, a significant improvement in overall nighttime QoV at the 12 months assessment was found.

Over 12 Years Single Institutional Experience Performing Percutaneous Hepatic Perfusion for Unresectable Liver Metastases.

Patients with unresectable hepatic metastases, from uveal or ocular melanoma, are challenging to treat with an overall poor prognosis. Although over the past decade significant advances in systemic therapies have been made, metastatic disease to the liver, especially from uveal melanoma, continues to be a poor prognosis. Percutaneous hepatic perfusion (PHP) is a safe, viable treatment option for these patients. PHP utilizes high dose chemotherapy delivered directly to the liver while minimizing systemic exposure and can be repeated up to 6 times. Isolation of the hepatic vasculature with a double-balloon catheter allows for high concentration cytotoxic therapy to be administered with minimal systemic adverse effects. A detailed description of the multidisciplinary treatment protocol used at an institution with over 12 years of experience is discussed and recommendations are given. A dedicated team of a surgical or medical oncology, interventional radiology, anesthesiology and a perfusionist allows PHP to be repeatedly performed as a safe treatment strategy for unresectable hepatic metastases.

ERCP and SARS-COV-2: an urgent procedure that should be immune.

BACKGROUND: Radical changes to clinical and endoscopy practice have been rapidly introduced following the spread of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Urgent endoscopies are, however, intended to proceed as normal with additional personal protective procedures. A perceived reduction in hospital attendances may suggest a number of urgently indicated endoscopic retrograde cholangio-pancreatographies (ERCPs) are being missed. Objectives and Methods: A review of all ERCPs carried out in a large tertiary referral endoscopy unit under healthcare restrictions was compared to the same time period in previous years. The intention was to determine if ERCPs are proceeding as normal or if there is a difference in referral characteristics. RESULTS: Under service restrictions (13 March to the end of April 2020), 55 ERCPs were performed compared with 87 ERCPs in 2019. Similar numbers to 2019 were also recorded in the preceding years. One case of coronavirus disease 2019 (COVID-19) was reported in a patient in the days following ERCP, with no cases notified among staff related to endoscopy. CONCLUSIONS: A reduction in ERCP referrals raises concern that a cohort of patients with significant biliary disease remain undetected. Whether this results in later, and more severe, presentation remains to be seen but a potential surge in such cases could significantly burden all future endoscopy planning services.

PRAGMATISM OF RANDOMIZED CLINICAL TRIALS ON RANIBIZUMAB FOR THE TREATMENT OF DIABETIC MACULAR EDEMA: Impact on Clinical Outcomes.

PURPOSE: To evaluate the pragmatism and generalizability of randomized clinical trials (RCTs) on ranibizumab for diabetic macular edema and determine whether clinical outcomes would differ based on whether or not patients fulfill the eligibility criteria of these RCTs. METHODS: Pragmatism and generalizability of three RCTs on ranibizumab for diabetic macular edema (DRCRnet Protocols I and T, and RESTORE) were rated using the PRECIS-2 tool. A cohort of consecutive patients with diabetic macular edema was assessed to determine whether clinical outcomes differed based on whether or not patients met the RCT eligibility criteria. Univariable and multivariable regression analyses, adjusted for baseline best-corrected visual acuity, central retinal thickness and number of injections received, were used. RESULTS: All RCTs were rated as being more pragmatic than explanatory, with DRCRnet trials being the most pragmatic. Of the 216 eyes (176 patients) included in the cohort, 63% would have met eligibility criteria for Protocol T, 61% for Protocol I, and 56% for RESTORE. When adjusted for best-corrected visual acuity, central retinal thickness, and number of ranibizumab injections received, there were no statistically significant differences in best-corrected visual acuity or central retinal thickness found between "eligible" and "ineligible" patients. CONCLUSION: Randomized clinical trials evaluating ranibizumab for diabetic macular edema were more pragmatic than explanatory. "Ineligible" patients still benefited from ranibizumab therapy.

Validation of a Model for Identification of Patients With Compensated Cirrhosis at High Risk of Decompensation.

BACKGROUND & AIMS: It is important to rapidly identify patients with advanced liver disease. Routine tests to assess liver function and fibrosis provide data that can be used to determine patients' prognoses. We tested the validated the ability of combined data from the ALBI and FIB-4 scoring systems to identify patients with compensated cirrhosis at highest risk for decompensation. METHODS: We collected data from 145 patients with compensated cirrhosis (91% Child A cirrhosis and median MELD scores below 8) from a cohort in Nottingham, United Kingdom, followed for a median 4.59 years (development cohort). We collected baseline clinical features and recorded decompensation events. We used these data to develop a model based on liver function (assessed by the ALBI score) and extent of fibrosis (assessed by the FIB-4 index) to determine risk of decompensation. We validated the model in 2 independent external cohorts (1 in Dublin, Ireland and 1 in Menoufia, Egypt) comprising 234 patients. RESULTS: In the development cohort, 19.3% of the patients developed decompensated cirrhosis. Using a combination of ALBI and FIB-4 scores, we developed a model that identified patients at low vs high risk of decompensation (hazard ratio [HR] for decompensation in patients with high risk score was 7.10). When we tested the scoring system in the validation cohorts, the HR for decompensation in patients with a high-risk score was 12.54 in the Ireland cohort and 5.10 in the Egypt cohort. CONCLUSION: We developed scoring system, based on a combination of ALBI and FIB-4 scores, that identifies patients at risk for liver decompensation. We validated the scoring system in 2 independent international cohorts (Europe and the Middle East), so it appears to apply to diverse populations.

Vitreomacular interface abnormalities in patients with diabetic macular oedema and their implications on the response to anti-VEGF therapy.

PURPOSE: To determine whether the presence of vitreomacular interface abnormalities (VMIA) in patients with diabetic macular oedema (DMO) modifies the response to ranibizumab. METHODS: Medical records and spectral-domain optical coherence tomography (SD-OCT) scans of consecutive patients with centre-involving DMO initiating therapy with ranibizumab between December 2013 and March 2014 at the Belfast Health and Social Care Trust were reviewed. Patients were identified through an electronic database. Demographics; systemic baseline characteristics; history of previous ocular surgery/laser; best-corrected visual acuity (BCVA), central retinal thickness (CRT) and stage of retinopathy at presentation; and BCVA, CRT and presence/absence of fluid at the last follow-up were recorded. OCT scans were reviewed by a masked investigator who graded them for the presence/absence of VMIA at baseline and during follow-up and for the change in the posterior hyaloid face during follow-up. The association between (1) VMIA at baseline and (2) the change in the posterior hyaloid face during the follow-up and functional/anatomical outcomes was evaluated. RESULTS: One hundred forty-six eyes of 100 patients (mean age 63.5 years) followed for a mean of 9 months (range 2-14 months; only 9/146 dropped to follow-up before month 6) were included. Statistically significant differences were observed at baseline in BCVA (p = 0.007), previous macular laser and panretinal photocoagulation (PRP) (p = 0.006) and previous cataract surgery (p = 0.01) between eyes with and without VMIA, with better levels of vision, higher frequency of macular laser and lower frequency of PRP in eyes where no VMIA was present. Multivariable regression analysis did not disclose any statistically significant associations between VMIA at baseline or change in the posterior hyaloid face during the follow-up and functional and anatomical outcomes following treatment. CONCLUSION: VMIA are associated with worse presenting vision in patients with DMO; VMIA or change in the posterior hyaloid face during the follow-up did not modify the response to ranibizumab in this study.

Disease outcomes in a cohort of women in Ireland infected by hepatitis C-contaminated anti-D immunoglobulin during 1970s.

BACKGROUND & AIM: In the mid-1990s, a group of Rh negative women was diagnosed with hepatitis C virus (HCV) genotype 1b infection, following administration of contaminated anti-D immunoglobulin in 1977-79. We aimed to describe their disease history and estimate the effect of selected host and treatment factors on disease progression. METHODS: We conducted a cohort study on the women infected with HCV. Information was collected from records at seven HCV treatment centres on demographics, treatment and health outcomes up to the 31st December 2013. We calculated cumulative incidence, case fatality, and sub hazard ratios (SHR) for disease progression using competing risks regression. RESULTS: Six hundred and eighty-two patients were included in the study. Among the chronically infected patients (n=374), 35% completed interferon-based antiviral treatment; 42% of whom had a sustained virological response. At the end of 2013, 19%, 1.9%, and 4.9% of chronically infected patients had developed cirrhosis, hepatocellular carcinoma, and liver-related death, respectively, compared with 10%, 0.8%, and 2.4% at the end of 2008. At the end of 2013, 321 (86%) of the chronically infected patients remained alive, 247 (77%) of whom were still chronically infected. Factors associated with increased cirrhosis rates included high alcohol intake (aSHR=4.9 [2.5-9.5]) and diabetes mellitus (aSHR=5.0 [2.9-8.8]). CONCLUSIONS: Development of liver-related outcomes accelerated with time, with the risk of cirrhosis, hepatocellular carcinoma, and liver-related death doubling in the last five years of follow-up, particularly in women with high alcohol consumption and diabetes mellitus. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of alcohol, and that data be collected on this cohort after a further five years to analyse the effect of subsequent antiviral treatment during this rapidly evolving period in HCV treatment history. LAY SUMMARY: In the mid-1990s, a group of women were diagnosed with chronic hepatitis C virus (HCV) infection following receipt of contaminated anti-D immunoglobulin between 1977 and 1979 in Ireland. Seventy-two (19%) developed cirrhosis and 18 had died from liver-related causes (5%) after 36years of infection. Disease progression accelerated in the last five years of follow-up, particularly in women with diabetes mellitus and high alcohol consumption. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of high alcohol consumption.

Increased soluble GPVI levels in cirrhosis: evidence for early in vivo platelet activation.

Cirrhosis is a consequence of prolonged liver injury and is characterised by extensive tissue fibrosis: the deposition of collagen-rich extracellular matrix. The haemostatic balance is disordered in cirrhosis and coagulation activation appears to promote fibrosis. In spite of recent studies demonstrating a role for anticoagulant therapy in preventing cirrhosis progression, there has not been a change in clinical practice, suggesting that physicians are reluctant to anticoagulate patients with cirrhosis due to bleeding risks. Platelets play an important role in facilitating coagulation. Glycoprotein VI (GPVI) is a platelet-specific collagen receptor that is shed from the platelet surface in a metalloproteinase-dependent manner in response to GPVI ligation and coagulation activation. Our aim was to use soluble GPVI levels to determine whether there was evidence for collagen and coagulation-induced platelet activation in early, well-compensated cirrhosis. Plasma soluble GPVI levels were quantified in 46 patients with mixed aetiology cirrhosis and 55 healthy controls using an immunoassay. In the cirrhosis group, soluble GPVI levels were significantly increased (5.8 ± 4.4 ng/ml, n = 46) compared to healthy controls (3.3 ± 3.4 ng/ml, n = 55, p < 0.05). This increase in soluble GPVI levels was still evident when levels were adjusted for platelet count (Healthy controls; 0.015 ± 0.018 ng/106 platelets/ml vs. cirrhosis; 0.048 ± 0.04 ng/106 platelets/ml, p < 0.0001). This study provides evidence for early platelet activation in patients with well-compensated cirrhosis. This may have translational implications for prognosis, treatment, and risk stratification.

Correlates of hepcidin and NTBI according to HFE status in patients referred to a liver centre.

BACKGROUND/AIMS: Innately low hepcidin levels lead to iron overload in HFE-associated hereditary haemochromatosis. METHODS: This study compared hepcidin and non-transferrin bound iron (NTBI) levels in untreated iron-loaded and non-iron-loaded C282Y homozygotes to levels in C282Y/H63D compound heterozygotes and individuals with other HFE genotypes associated with less risk of iron overload. RESULTS: As the genotypic risk for iron overload increased, transferrin saturation and serum NTBI levels increased while serum hepcidin levels decreased. Overweight and obese male C282Y homozygotes had significantly higher hepcidin levels than male C282Y homozygotes with a normal BMI. Pearson product-moment analysis showed that serum hepcidin levels significantly correlated with HFE status, serum ferritin, age, NTBI, transferrin saturation, gender and BMI. Subsequent multiple regression analysis showed that HFE status and serum ferritin were significant independent correlates of serum hepcidin levels. CONCLUSIONS: In summary, this study has shown that while serum ferritin and HFE status are the most important determinants of hepcidin levels, factors such age, gender, BMI, transferrin saturation and NTBI all interact closely in the matrix of homeostatic iron balance.

Blood alanine aminotransferase levels >1,000 IU/l - causes and outcomes.

Standard medical education dictates that the vast majority of cases of an alanine aminotransferase (ALT) level >1,000 IU/l will be due to acute ischaemia, acute drug-induced liver injury (DILI) (usually paracetamol) or acute viral hepatitis. There are very few references in the literature to other potential causes of an ALT >1,000 IU/l nor to the prognosis ascribed to each aetiology. In this study, we have confirmed that the main causes of a dramatic ALT rise are ischaemic liver injury, DILI and viral hepatitis. Common bile duct stones and hepatitis E are two causes for which there needs to be a high index of suspicion as the necessary tests may not be in the clinician's first-line investigation panel. Failing to find a cause and determining that the cause was ischaemic both have poor prognostic implications.

Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team.

BACKGROUND & AIMS: Hepatocellular cancer (HCC) commonly complicates chronic liver disease and increases in incidence have been reported despite falling prevalences of viral hepatitis. METHODS: Following the introduction of centralised specialist teams to manage patients with cancer in England, we characterised the demographics of patients with HCC referred to the Newcastle-upon-Tyne Hospitals NHS Foundation Trust between 2000 and 2010. Regional HCC mortality data was from Public Health England. RESULTS: HCC related mortality in the region rose 1.8 fold in 10 years, from 2.0 to 3.7 per 100,000. 632 cases were reviewed centrally, with 2-3 fold increases in referrals of patients with associated hepatitis C, alcoholic liver disease or no chronic liver disease and a >10 fold increase in HCC associated with non-alcoholic fatty liver disease (NAFLD). By 2010 NAFLD accounted for 41/118 (34.8%) cases. Irrespective of associated etiologies, metabolic risk factors were present in 78/118 (66.1%) cases in 2010, associated with regional increases in obesity and diabetes. Median overall survival was just 10.7 months. Although patients with NAFLD associated HCC were older (71.3 yr vs. 67.1 yr; p<0.001) and their cancers less often detected by surveillance, their survival was similar to other etiologies. This was attributed to significantly higher incidental presentation (38.2%) and lower prevalence of cirrhosis (77.2%). CONCLUSIONS: HCC related mortality is increasing, with typical patients being elderly with metabolic risk factors. The prognosis for most of the cases is poor, but older patients with co-morbidities can do well, managed, within a specialist multidisciplinary team if their cancer is detected pre-symptomatically.

In vitro blood cell responsiveness to IFN-α predicts clinical response independently of IL28B in hepatitis C virus genotype 1 infected patients.

BACKGROUND: Treatment with interferon-alpha (IFN-α) and ribavirin successfully clears hepatitis C virus (HCV) infection in 50% of patients infected with genotype 1. Addition of NS3-4A protease inhibitors (PIs) increases response rates but results in additional side effects and significant economic costs. Here, we hypothesised that in vitro responsiveness of peripheral blood mononuclear cells (PBMCs) to IFN-α stimulation would identify patients who achieved sustained virological response (SVR) on dual therapy alone and thus not require addition of PIs. METHODS: PBMCs were isolated from HCV infected patients (n = 42), infected with either HCV genotype 1 or genotype 3, before commencing therapy and stimulated in vitro with IFN-α. Expression of the IFN stimulated genes (ISGs) PKR, OAS and MxA was measured and correlated with subsequent treatment response and IL28B genotype. RESULTS: Genotype 1 infected patients who achieved SVR had significantly higher pre-treatment expression of PKR (p = 0.0148), OAS (p = 0.0019) and MxA (p = 0.0019) in IFN-α stimulated PBMCs, compared to genotype 1 infected patients who did not achieve SVR or patients infected with genotype 3, whose in vitro ISG expression did not correlate with clinical responsiveness. IL28B genotype (rs12979860) did not correlate with endogenous or IFN-α stimulated ISG responsiveness. CONCLUSIONS: In vitro responsiveness of PBMCs to IFN-α from genotype 1 infected patients predicts clinical responsiveness to dual therapy, independently of IL28B genotype. These results indicate that this sub-group of HCV infected patients could be identified pre-treatment and successfully treated without PIs, thus reducing adverse side effects and emergence of PI resistant virus while making significant economic savings.

Clinical but not histological factors predict long-term prognosis in patients with histologically advanced non-decompensated alcoholic liver disease.

BACKGROUND: Alcoholic liver disease (ALD) is a significant threat to public health and a leading cause of death. Despite this, the long-term clinical course and predictive factors of survival in histologically advanced ALD are not well described. AIMS: The aim of this study was to identify clinical and histological factors that predict long-term (15-year) survival in outpatients with histologically advanced non-decompensated ALD. METHODS: Patients (n = 134) with biopsy-proven histologically advanced (stage III or IV) ALD were followed up for 15 years or until death or orthotopic liver transplantation. At baseline, clinical and laboratory data were collected. On biopsy, the degree of fibrosis as well as other histological features (fat type and severity, lymphocyte and neutrophil infiltration) were scored semiquantitatively. RESULTS: Most patients were male (72%) with a median age 51 (46-57). Overall, the 5-, 10- and 15-year survival was 63, 36 and 24% respectively. In multivariate analysis, persistent drinking (P = 0.01), smoking (P = 0.03), age (P = 0.01) and serum albumin at baseline (P = 0.001) were associated with significantly increased risk of death. Persistent drinking was associated with the highest risk. No histological features, including whether the stage of ALD was bridging fibrosis or cirrhosis, correlated with prognosis. CONCLUSION: In outpatients with biopsy-proven histologically advanced non-decompensated ALD, clinical but not histological factors determine prognosis. Persistent alcohol intake is the strongest predictor and smoking habit, age and serum albumin are also independently prognostic. Abstinence from alcohol and smoking cessation should be the priorities in the long-term management of ALD.

Immediate sequential bilateral cataract surgery (ISBCS): A single-site experience of 41 patients during the COVID-19 pandemic.

Background: The practice of immediate sequential bilateral cataract surgery (ISBCS) was more widely adopted in the UK during the COVID-19 pandemic, in response to limited surgical capacity and the risk of nosocomial infection. This study reports on a single site experience of ISBCS in Northern Ireland. Methods: Data was collected prospectively between 17th November 2020 and 30th November 2021. The ISBCS surgical protocol, recommended by RCOphth and UKISCRS, was followed. Primary outcomes measures were: postoperative visual acuity (VA), refractive prediction accuracy, intraoperative and postoperative complications. Results: Of 41 patients scheduled, 39 patients completed ISBCS and two patients underwent unilateral surgery (n=80 eyes). Mean age at the time of surgery was 71.6 years (standard deviation (SD) ±11.8 years). Median preoperative VA was 0.8 logMAR (range: PL to 0.2 logMAR). Seventeen (20.9%) eyes were highly myopic and 9 (11.1%) eyes were highly hypermetropic. Median cumulative dissipated phacoemulsification energy was 15.7 sec (range: 1.8 sec to 83.4 sec). Median case time was 10.4 min (range: 4.3 min to 37.1 min).One eye (1.3%) developed iritis secondary to a retained tiny cortical fragment. Four eyes (5.0%, n=3 patients) developed cystoid macular oedema, with full resolution. On wide field imaging, an asymptomatic unilateral peripheral suprachoroidal haemorrhage was noted in two highly myopic patients (axial lengths of 27.01mm and 25.05mm respectively). The posterior pole was spared, and both resolved spontaneously without any visual impairment. Conclusions: In our initial experience, ISBCS was found to be a safe approach to cataract surgery. Our patient cohort included eyes with dense cataracts and high ametropia. Further studies are required to assess patient reported outcome measures and the possible economic benefits of ISBCS in our local population.

Accuracy of Toric Intraocular Lens Formulas With Measured Posterior Corneal Astigmatism of Different Orientations.

PURPOSE: To assess whether the use of measured posterior corneal astigmatism (PCA) values improves the prediction accuracy of toric intraocular lens power formulas, compared to predicted PCA values, when the orientation of the steep axis of PCA is non-vertical. DESIGN: Retrospective observational cohort study. METHODS: Four hundred eighteen eyes of 344 patients were included in the study. Prediction errors (PE) for postoperative refractive astigmatism at 4 weeks postoperatively were determined using vector analysis and compared for the following toric intraocular lens power formulas: Barrett Toric with predicted posterior corneal astigmatism (PPCA); Barrett Toric with measured posterior corneal astigmatism (MPCA); EVO Toric PPCA; EVO Toric MPCA; Holladay I with Abulafia-Koch regression. Subgroup analysis compared PEs for eyes with a vertically orientated steep axis of PCA (60-120°) to eyes with a non-vertically orientated steep axis of PCA. SETTING: Cathedral Eye Clinic, Belfast, United Kingdom and Tan Tock Seng Hospital, Singapore. RESULTS: Standard keratometry was with-the-rule in 48% of eyes, while the steep PCA axis was vertically orientated in 91% of eyes. For all eyes, EVO-PPCA had a smaller mean absolute error than Barrett-MPCA, Barrett-PPCA, and Abulafia-Koch (P < .01 for all). EVO-PPCA had the highest percentage of eyes within 0.50D of predicted postoperative astigmatism for eyes with vertical PCA (61%), while EVO-MPCA had the highest percentage for eyes with non-vertical PCA (54%). EVO-MPCA had the smallest centroid error for all eyes, and the subgroups (P < .01 for all). Eyes with non-vertical PCA had a lower percentage within 0.50D than eyes with vertical PCA when using PPCA (43% vs 61%, P = .034), but there was no significant difference between these groups when MPCA is used for eyes with non-vertical PCA (54% vs 61%, P = .40). CONCLUSIONS: When the steep axis of posterior corneal astigmatism is not vertically orientated, the use of measured posterior keratometry values improves prediction accuracy.

White cell count and platelet count associate with histological alcoholic hepatitis in jaundiced harmful drinkers.

BACKGROUND: Patients with suspected alcoholic hepatitis and a Discriminant Function ≥32 underwent liver biopsy to confirm the diagnosis. Of these (n = 58), 43 had histological features of alcoholic hepatitis and 15 (25%) did not.We aimed to determine the laboratory features that differentiated those patients with a histological diagnosis of alcoholic hepatitis from those without, and assess potential clinical utility. METHODS: Laboratory investigations at presentation for each of the histologically confirmed cases of alcoholic hepatitis (n = 43) were compared to those without (n = 15) to determine whether there were differences between the two groups. Univariate analysis was by Mann Whitney U Test and Multivariate analysis was by a stepwise approach. RESULTS: White cell count (16.2 ± 10.5 v 6.9 ± 3.5 (× 109/L); p = 0.0001) and platelet count (178 ± 81 v 98.4 ± 43 (× 109/L); p = 0.0005) were higher in the patients with histological features of alcoholic hepatitis than in those without. The area under the ROC curve for AH diagnosis was estimated to be 0.83 (0.73, 0.94) and 0.81 (0.69, 0.93) for white cell count and platelet count respectively. CONCLUSIONS: Clinicians cannot accurately differentiate patients with or without alcoholic hepatitis without liver biopsy. This is critically important when deciding on specific therapies such as corticosteroids or when interpreting data from future trials in which biopsy is not mandated. In situations where liver biopsy is unsuitable or unavailable the white cell and platelet counts can be used to determine the likelihood of histological alcoholic hepatitis and guide treatment.

Visual performance and subjective experience 3 months and 12 months after combined implantation of 2 new complementary continuous phase multifocal intraocular lenses.

PURPOSE: To assess the 3-month and 12-month postoperative visual performance and subjective quality of vision (QoV) after combined implantation of complementary continuous phase multifocal intraocular lenses (IOLs). SETTING: Private practice, United Kingdom. DESIGN: Case series. METHODS: The study enrolled 44 patients undergoing phacoemulsification with implantation of an Artis Symbiose Mid in the dominant eye and an Artis Symbiose Plus in the nondominant eye. Refraction, uncorrected distance visual acuity (UDVA), corrected distance visual acuity, uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), electronic reading desk, and a QoV questionnaire were evaluated at 3 months and 12 months postoperatively. RESULTS: The mean binocular UDVA was -0.06 ± 0.08 logMAR and -0.07 ± 0.06 logMAR at 3 months and 12 months ( P = .097), respectively. The mean binocular UIVA was 0.03 ± 0.13 logMAR and 0.03 ± 0.10 logMAR ( P = 1.0), respectively. The mean binocular UNVA was 0.07 ± 0.10 logMAR and 0.07 ± 0.08 logMAR ( P = .875), respectively. There was a significant improvement in QoV for both day and night between 3 and 12 months, with a significant reduction in halos at 12 months. Spectacle independence was reported in 93.2% of cases at 12 months. CONCLUSIONS: The Artis Symbiose Mid and Plus IOL combined implantation provided an excellent range of uncorrected vision at 3 and 12 months. There was a significant improvement in QoV and less halos at 12 months. This IOL combination provided very high rates of complete spectacle independence.

Impact of minimum unit pricing on alcohol-related hospital outcomes: systematic review.

OBJECTIVE: To determine the impact of minimum unit pricing (MUP) on the primary outcome of alcohol-related hospitalisation, and secondary outcomes of length of stay, hospital mortality and alcohol-related liver disease in hospital. DESIGN: Databases MEDLINE, Embase, Scopus, APA Psycinfo, CINAHL Plus and Cochrane Reviews were searched from 1 January 2011 to 11 November 2022. Inclusion criteria were studies evaluating the impact of minimum pricing policies, and we excluded non-minimum pricing policies or studies without alcohol-related hospital outcomes. The Effective Public Health Practice Project tool was used to assess risk of bias, and the Bradford Hill Criteria were used to infer causality for outcome measures. SETTING: MUP sets a legally required floor price per unit of alcohol and is estimated to reduce alcohol-attributable healthcare burden. PARTICIPANT: All studies meeting inclusion criteria from any country INTERVENTION: Minimum pricing policy of alcohol PRIMARY AND SECONDARY OUTCOME MEASURES: RESULTS: 22 studies met inclusion criteria; 6 natural experiments and 16 modelling studies. Countries included Australia, Canada, England, Northern Ireland, Ireland, Scotland, South Africa and Wales. Modelling studies estimated that MUP could reduce alcohol-related admissions by 3%-10% annually and the majority of real-world studies demonstrated that acute alcohol-related admissions responded immediately and reduced by 2%-9%, and chronic alcohol-related admissions lagged by 2-3 years and reduced by 4%-9% annually. Minimum pricing could target the heaviest consumers from the most deprived groups who tend to be at greatest risk of alcohol harms, and in so doing has the potential to reduce health inequalities. Using the Bradford Hill Criteria, we inferred a 'moderate-to-strong' causal link that MUP could reduce alcohol-related hospitalisation. CONCLUSIONS: Natural studies were consistent with minimum pricing modelling studies and showed that this policy could reduce alcohol-related hospitalisation and health inequalities. PROSPERO REGISTRATION NUMBER: CRD42021274023.

A hybrid soft material robotic end-effector for reversible in-space assembly of strut components.

Based on the NASA in-Space Assembled Telescope (iSAT) study (Bulletin of the American Astronomical Society, 2019, 51, 50) which details the design and requirements for a 20-m parabolic in-space telescope, NASA Langley Research Center (LaRC) has been developing structural and robotic solutions to address the needs of building larger in-space assets. One of the structural methods studied involves stackable and collapsible modular solutions to address launch vehicle volume constraints. This solution uses a packing method that stacks struts in a dixie-cup like manner and a chemical composite bonding technique that reduces weight of the structure, adds strength, and offers the ability to de-bond the components for structural modifications. We present in this paper work towards a soft material robot end-effector, capable of suppling the manipulability, pressure, and temperature requirements for the bonding/de-bonding of these conical structural components. This work is done to investigate the feasibility of a hybrid soft robotic end-effector actuated by Twisted and Coiled Artificial Muscles (TCAMs) for in-space assembly tasks. TCAMs are a class of actuator which have garnered significant recent research interest due to their allowance for high force to weight ratio when compared to other popular methods of actuation within the field of soft robotics, and a muscle-tendon actuation design using TCAMs leads to a compact and lightweight system with controllable and tunable behavior. In addition to the muscle-tendon design, this paper also details the early investigation of an induction system for adhesive bonding/de-bonding and the sensors used for benchtop design and testing. Additionally, we discuss the viability of Robotic Operating System 2 (ROS2) and Gazebo modeling environments for soft robotics as they pertain to larger simulation efforts at LaRC. We show real world test results against simulation results for a method which divides the soft, continuous material of the end-effector into discrete links connected by spring-like joints.