Automated confidence estimation in deep learning auto-segmentation for brain organs at risk on MRI for radiotherapy.

PURPOSE: We have built a novel AI-driven QA method called AutoConfidence (ACo), to estimate segmentation confidence on a per-voxel basis without gold standard segmentations, enabling robust, efficient review of automated segmentation (AS). We have demonstrated this method in brain OAR AS on MRI, using internal and external (third-party) AS models. METHODS: Thirty-two retrospectives, MRI planned, glioma cases were randomly selected from a local clinical cohort for ACo training. A generator was trained adversarialy to produce internal autosegmentations (IAS) with a discriminator to estimate voxel-wise IAS uncertainty, given the input MRI. Confidence maps for each proposed segmentation were produced for operator use in AS editing and were compared with "difference to gold-standard" error maps. Nine cases were used for testing ACo performance on IAS and validation with two external deep learning segmentation model predictions [external model with low-quality AS (EM-LQ) and external model with high-quality AS (EM-HQ)]. Matthew's correlation coefficient (MCC), false-positive rate (FPR), false-negative rate (FNR), and visual assessment were used for evaluation. Edge removal and geometric distance corrections were applied to achieve more useful and clinically relevant confidence maps and performance metrics. RESULTS: ACo showed generally excellent performance on both internal and external segmentations, across all OARs (except lenses). MCC was higher on IAS and low-quality external segmentations (EM-LQ) than high-quality ones (EM-HQ). On IAS and EM-LQ, average MCC (excluding lenses) varied from 0.6 to 0.9, while average FPR and FNR were ≤0.13 and ≤0.21, respectively. For EM-HQ, average MCC varied from 0.4 to 0.8, while average FPR and FNR were ≤0.37 and ≤0.22, respectively. CONCLUSION: ACo was a reliable predictor of uncertainty and errors on AS generated both internally and externally, demonstrating its potential as an independent, reference-free QA tool, which could help operators deliver robust, efficient autosegmentation in the radiotherapy clinic.

Dosimetric impact of contour editing on CT and MRI deep-learning autosegmentation for brain OARs.

PURPOSE: To establish the clinical applicability of deep-learning organ-at-risk autocontouring models (DL-AC) for brain radiotherapy. The dosimetric impact of contour editing, prior to model training, on performance was evaluated for both CT and MRI-based models. The correlation between geometric and dosimetric measures was also investigated to establish whether dosimetric assessment is required for clinical validation. METHOD: CT and MRI-based deep learning autosegmentation models were trained using edited and unedited clinical contours. Autosegmentations were dosimetrically compared to gold standard contours for a test cohort. D1%, D5%, D50%, and maximum dose were used as clinically relevant dosimetric measures. The statistical significance of dosimetric differences between the gold standard and autocontours was established using paired Student's t-tests. Clinically significant cases were identified via dosimetric headroom to the OAR tolerance. Pearson's Correlations were used to investigate the relationship between geometric measures and absolute percentage dose changes for each autosegmentation model. RESULTS: Except for the right orbit, when delineated using MRI models, the dosimetric statistical analysis revealed no superior model in terms of the dosimetric accuracy between the CT DL-AC models or between the MRI DL-AC for any investigated brain OARs. The number of patients where the clinical significance threshold was exceeded was higher for the optic chiasm D1% than other OARs, for all autosegmentation models. A weak correlation was consistently observed between the outcomes of dosimetric and geometric evaluations. CONCLUSIONS: Editing contours before training the DL-AC model had no significant impact on dosimetry. The geometric test metrics were inadequate to estimate the impact of contour inaccuracies on dose. Accordingly, dosimetric analysis is needed to evaluate the clinical applicability of DL-AC models in the brain.

Cross-cultural adaptation, translation, and validation of the Arabic version of the short form of Neurogenic Bladder Symptoms Score.

BACKGROUND: The Neurogenic Bladder Symptom Score-Short Form (NBSS-SF) evaluates the impact of disease-specific symptoms on the quality of life (QoL) in individuals with neurogenic bladder (NB). There is no data on the validity and reliability of the NBSS-SF questionnaire in the Arabic language, so this study aimed at providing the translation, cultural adaptation, and validation of the Arabic NBSS-SF in patients with multiple sclerosis (MS) and spinal cord injury (SCI). METHODS: The original English language version of the NBSS-SF was translated into Arabic according to the cultural and linguistic adaptation algorithm. People with SCI and MS completed the NBSS-SF, demographic and clinical information, and Qualiveen QoL questionnaire. Responses were recorded twice within a 14-day period. Psychometric properties such as content validity, construct validity, internal consistency, and test-retest reliability were tested. Internal consistency and test-retest reliability was evaluated using Cronbach's alpha, and the intraclass correlation coefficient (ICC), respectively. Construct validity was assessed by comparing the NBSS-SF with the Qualiveen questionnaire. RESULTS: Thirty-nine patients with MS and 97 with SCI participated in the study. The internal consistency for the overall NBSS-SF score (Cronbach's α of 0.82) and for each subdomain was variable (urinary incontinence 0.82; storage/voiding 0.73; consequences 0.53). ICC was 0.93 for the overall score and 0.96 for the urinary incontinence subdomain, 0.74 for storage/voiding, and 0.91 for consequences. The correlation analysis showed a significantly strong correlation between the QoL item of NBSS-SF and the Qualiveen total score (r = 0.72, p < 0.000). There was a significant moderate positive correlation between the total scores on the Arabic version of the NBSS-SF and the subdomains of the Qualiveen, including limitations (r = 0.51, p = 0.04), fears (r = 0.57, p = 0.04), feelings (r = 0.46, p = 0.01), and constraints (r = 0.59, p = 0.03). CONCLUSIONS: Our results showed that the Arabic version of NBSS-SF is a valid and reliable instrument for evaluating neurogenic lower urinary tract dysfunction symptoms in the Arabic population suffering from SCI and MS.

Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97.

Sigma-2 receptor (S2R) is a S2R ligand-binding site historically associated with reportedly 21.5 kDa proteins that have been linked to several diseases, such as cancer, Alzheimer's disease, and schizophrenia. The S2R is highly expressed in various tumors, where it correlates with the proliferative status of the malignant cells. Recently, S2R was reported to be the transmembrane protein TMEM97. Prior to that, we had been investigating the translocator protein (TSPO) as a potential 21.5 kDa S2R candidate protein with reported heme and sterol associations. Here, we investigate the contributions of TMEM97 and TSPO to S2R activity in MCF7 breast adenocarcinoma and MIA PaCa-2 (MP) pancreatic carcinoma cells. Additionally, the role of the reported S2R-interacting partner PGRMC1 was also elucidated. Proximity ligation assays and co-immunoprecipitation show a functional association between S2R and TSPO. Moreover, a close physical colocalization of TMEM97 and TSPO was found in MP cells. In MCF7 cells, co-immunoprecipitation only occurred with TMEM97 but not with PGRMC1, which was further confirmed by confocal microscopy experiments. Treatment with the TMEM97 ligand 20-(S)-hydroxycholesterol reduced co-immunoprecipitation of both TMEM97 and PGRMC1 in immune pellets of immunoprecipitated TSPO in MP cells. To the best of our knowledge, this is the first suggestion of a (functional) interaction between TSPO and TMEM97 that can be affected by S2R ligands.

Safety of a Novel Obstructive Sleep Apnea Triage Tool for Postoperative Orthopedic Surgery Patients.

PURPOSE: The purpose of this quality improvement project is to provide a tool for effective and safe triage of postoperative patients in the postanesthesia care unit with known or suspected obstructive sleep apnea (OSA) at an academic orthopedic hospital in New York City. DESIGN: The structure of this project was observational after implementation of a novel OSA triage tool. METHODS: Results were reported from a single center experience in a hospital where there was no existing standard assessment tool consistently used to triage patients with either known or suspected OSA in the postoperative period. Adult patients who underwent orthopedic surgery between October 2018 and February 2020 and who had a known or suspected history of OSA were included. After admission to the postanesthesia care unit (PACU) and upon meeting their modified Aldrete criteria or after 2 hours had elapsed, the PACU primary provider used the OSA triage tool to assess whether the patient had a high or low risk of respiratory deterioration after discharge from the PACU related to OSA. Patients without high-risk criteria were discharged from the PACU to a medical/surgical unit. For patients with high-risk criteria, the PACU provider requested critical care consultation to determine each patient's appropriate hospital disposition upon PACU discharge. FINDINGS: Over the course of the study period, 216 patients were evaluated using the OSA triage tool: 53.2% of the cohort was male, median BMI was 36.3 kg/m2, and 80.1% had a prior diagnosis of obstructive sleep apnea. Patients underwent a variety of orthopedic surgeries with 23.6% having undergone hip surgery, 51.4% knee surgery, 13.4% spine surgery, 9.7% shoulder surgery, and 1.9% foot or ankle surgery. Notably, with the use of this tool, only 12.5% of patients met criteria for critical care consult and 91.7% were admitted to the floor from the PACU. Rapid response for respiratory complications were not observed in any of the patients. There were only three patients who required critical care evaluation after PACU discharge. An anonymous survey completed by PACU nurse practitioners and anesthesiologists revealed a 96.8% self-reported satisfaction with OSA triage tool. CONCLUSION: We demonstrated that use of a OSA triage tool in the single-center orthopedic PACU at NYULH is potentially a safe and effective method of triaging patients with known or suspected OSA to acute care beds versus higher levels of care.

TNAP limits TGF-ß-dependent cardiac and skeletal muscle fibrosis by inactivating the SMAD2/3 transcription factors.

Fibrosis is associated with almost all forms of chronic cardiac and skeletal muscle diseases. The accumulation of extracellular matrix impairs the contractility of muscle cells contributing to organ failure. Transforming growth factor ß (TGF-ß) plays a pivotal role in fibrosis, activating pro-fibrotic gene programmes via phosphorylation of SMAD2/3 transcription factors. However, the mechanisms that control de-phosphorylation of SMAD2 and SMAD3 (SMAD2/3) have remained poorly characterized. Here, we show that tissue non-specific alkaline phosphatase (TNAP, also known as ALPL) is highly upregulated in hypertrophic hearts and in dystrophic skeletal muscles, and that the abrogation of TGF-ß signalling in TNAP-positive cells reduces vascular and interstitial fibrosis. We show that TNAP colocalizes and interacts with SMAD2. The TNAP inhibitor MLS-0038949 increases SMAD2/3 phosphorylation, while TNAP overexpression reduces SMAD2/3 phosphorylation and the expression of downstream fibrotic genes. Overall our data demonstrate that TNAP negatively regulates TGF-ß signalling and likely represents a mechanism to limit fibrosis.

Acute pancreatitis in patients with COVID-19 is more severe and lethal: a systematic review and meta-analysis.

BACKGROUND: Emerging evidence suggests an association between acute pancreatitis and COVID-19. Our objective is to conduct a systematic review and meta-analysis to evaluate whether COVID-19 affects the severity and outcomes associated with acute pancreatitis. METHODS: Cochrane guidelines and PRISMA statement were followed for this review. Digital dissertation bases were searched and all studies comparing the outcomes of acute pancreatitis amongst patients with and without COVID-19 were included. We compared the etiology, severity, length of hospital stay and mortality associated with acute pancreatitis in patients with and without COVID-19. RESULTS: Four observational studies with a total of 2,419 patients were included in the review. Presence of COVID-19 significantly increased the odds of mortality (OR 4.10, 95% CI 2.03-8.29) in patients with acute pancreatitis. These patients also had an increased incidence of severe pancreatitis (OR 3.51, 95% CI 1.19-10.32), necrotizing pancreatitis (OR 1.84, 95% CI 1.19-2.85) and a longer length of hospital stay (OR 2.88, 95% CI 1.50-5.52), compared to non-COVID patients. Patients with COVID-19 were more likely to have an unknown or idiopathic etiology of acute pancreatitis (OR 4.02, 95% CI 1.32-12.29), compared to non-COVID-19 patients. CONCLUSION: Current evidence suggests that COVID-19 adversely impacts the morbidity and mortality associated with acute pancreatitis. SARS-CoV-2 may be a causative agent for acute pancreatitis. Further population-based studies are needed to confirm or refute these findings.

A delay in colonoscopy after positive fecal tests leads to higher incidence of colorectal cancer: A systematic review and meta-analysis.

BACKGROUND AND AIM: A delay in performing colonoscopies after positive fecal tests in a screening program may risk neoplastic progression. Our objective is to conduct a systematic review and meta-analysis to evaluate the effects of timing of a colonoscopy after a positive fecal test on the detection of colorectal cancer. METHODS: Cochrane guidelines and PRISMA statement were followed for this review. Digital dissertation databases were searched from inception to June 1, 2020, and all studies reporting the detection rates of colorectal cancer on the basis of different time intervals between a positive fecal test and the post-test colonoscopy were included. We compared the detection rates of colorectal cancer (overall and advanced-stage) and advanced adenoma based on different time intervals. RESULTS: A total of 361 637 patients from six observational studies were included for the analysis. The odds of detecting any colorectal cancer (odds ratio [OR] 1.58, 95% confidence interval [CI] 1.23-2.03, P < 0.001), advanced-stage colorectal cancer (OR 2.16, 95% CI 1.47-3.16, P < 0.001), or advanced adenomas (OR 1.17, 95% CI 1.06-1.28, P = 0.001) are significantly higher if the colonoscopies are performed after 6 months from a positive fecal test, compared with within 6 months. There was no significant difference in the detection rates based on a 1-month, a 2-month, or a 3-month cut-off. CONCLUSIONS: A delay of colonoscopies beyond 6 months after positive fecal tests is associated with a higher odds of detecting colorectal cancer. A timely follow up of patients with positive fecal tests is warranted.

MELD-Na Is More Strongly Associated with Risk of Infection and Outcomes Than Other Characteristics of Patients with Cirrhosis.

BACKGROUND AND AIMS: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality. METHODS: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay. RESULTS: The study cohort of 1112 patients included 33% women with a mean age of 56 ± 10 years. Infections were common (20%), with respiratory and urinary tract infections the most frequent. We did not observe a difference in the incidence of infection on admission based on patient demographic factors such as race/ethnicity or estimated household income. Infections on admission were associated with greater short-term mortality (12% vs 4% in-hospital and 14% vs 7% 30-day), longer length of stay (6 vs 3 days), intensive care unit admission (28% vs 18%), and acute-on-chronic liver failure (10% vs 2%) (p < 0.01 for all). Nosocomial infections were relatively uncommon (4%), but more frequent among patients admitted to the intensive care unit. Antibiotic resistance was common (38%), but not associated with negative outcomes. CONCLUSION: We did not identify demographic risk factors for infection, but did confirm its morbid effect among patients with cirrhosis in safety-net hospitals.

Diabetic Foot Care Knowledge and Practices in Rural North India: Insights for Preventive Podiatry.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most dreaded complications of Type 2 Diabetes Mellitus (T2DM). Preventive podiatry is most efficient way of minimising DFU. The main aim of the study was to assess the knowledge and foot care practices among patients living with T2DM concerning the DFU. MATERIALS AND METHODS: We conducted a cross-sectional study in a rural-area of Haryana, India between January to March 2019 amongst 416 people living with T2DM after using multistage random sampling. A pre-tested, structured survey instrument prepared from the recommendation of the American College of Foot and Ankle Surgeons and the Diabetes UK was used after Hindi translation as per standard protocol. The knowledge and practices were classified as good, satisfactory and poor if the total score was between 8-11, 6-7 and <6. RESULTS: 14.2% had a previous history of DFU. The prevalence of good, satisfactory and poor knowledge was 63.5%, 12.5% and 24.0%. Further, 46.7%, 32.7% and 20.6% respondents depicted good, satisfactory and poor practices regarding foot care. On multivariate binary logistic regression analysis, younger age group, higher education, Per capita family income in INR, Blood glucose levels, HbA1c Levels, physical activity and previous history of DFU emerged as significant predictors of good foot-care knowledge and practices. CONCLUSION: There is an evident gap between foot-care knowledge and practices that should be addressed through comprehensive behaviour change strategies. Comprehensive risk-assessments for diabetes associated complications needs to be piloted at community level to assess the feasibility.

Protein complexes including PGRMC1 and actin-associated proteins are disrupted by AG-205.

PGRMC1 is a protein from the MAPR family with a range of cellular functions. PGRMC1 has been described to play a role in fertility, neuroprotection, steroidogenesis, membrane trafficking and in cancer cell biology. PGRMC1 represents a likely key regulator of cell metabolism and proliferation, as well as a potential target for anti-cancer therapies. To further understand the functions of PGRMC1 and the mechanism of the small molecule inhibitor of PGRMC1, AG-205, proteins differentially bound to PGRMC1 were identified following AG-205 treatment of MIA PaCa-2 cells. Our results suggest that AG-205 influences PGRMC1 interactions with the actin cytoskeleton. The binding of two PGRMC1-associated proteins that support this, RACK1 and alpha-Actinin-1, was reduced following AG-205 treatment. The biology associated with PGRMC1 binding partners identified here merits further investigation.

Oral Delivery of Teriparatide Using a Nanoemulsion System: Design, in Vitro and in Vivo Evaluation.

PURPOSE: Investigate the possibility of delivering teriparatide orally using nanoemulsion. METHOD: Teriparatide was allowed to interact with chitosan in the presence of HPßCD.The formed polyelectrolyte complex (PEC) was characterized by DSC, FTIR, DLS and for entrapment efficiency. PEC was the incorporated in an oil phase consisting of Oleic Acid, Labrasol and Plurol Oleique to form a nanoemulsion. This preparation was characterized for refractive index, viscosity, pH, conductivity, particle size, and morphology.Bioavailability of the preparation was evaluated using rabbits against SC injection. The efficacy of the formula was tested using ovariectomized rats (an osteoporosis animal model) and mechanical and histological tests were conducted on their bones. The stability of the preparation was evaluated by storing samples at 4o C, 25o C and 40o C for three months. RESULTS: PEC testing demonstrate a complex formation with particle size of 208 nm, zeta potential of +17 mV and entrapment efficiency of 49%. For the nanoemulsion, the results demonstrate the formation of a nano-sized dispersed system (108 nm) with a drug loading of 98% and a percent protection of 90% and 71% in SGF and SIF respectively. Bioavailability results showed a sustained release profile was achieved following the oral formulation administration. Efficacy studies showed improvement in the strength, thickness and connectivity of bones. Short-term stability study demostrated that the nanoemulsion is mostly stable at 4o C. CONCLUSION: These findings demonstrate the ability of delivering Teriparatide orally using oleic acid based dispersion in combination with chitosan PEC.

Risk Factors, Management, and Outcomes of Pyogenic Liver Abscess in a US Safety Net Hospital.

BACKGROUND: The causes and management of pyogenic liver abscess (PLA) have undergone multiple changes over the past decades. It is a relatively rare disease in the USA, and its incidence rate in the USA is increasing. The last US community hospital experience of PLA was published in 2005. We performed a retrospective study of patients admitted with PLA to an urban safety net hospital. AIMS: To ascertain risk factors, management approaches, and outcomes of PLA. METHODS: Electronic medical record was queried for diagnosis codes related to PLA during the years 2009-2018. Clinical information was compiled in an electronic database which was later analyzed. Main study outcomes were in-hospital mortality, 30-day readmission rate, and intensive care utilization rate. RESULTS: A total of 77 patients with PLA were admitted in the study period. Most common risk factors were diabetes mellitus (23.4%), previous liver surgery (20.7%), and hepatic malignancy (16.9%). 89% of patients were treated with percutaneous drainage or aspiration, and surgical drainage was reserved for other with other indications for laparotomy. In-hospital mortality, 30-day readmission, and intensive care utilization rates were 2.6%, 7% and 22%, respectively. Median length of stay was 11 days (inter-quartile range 7). Rate of antimicrobial resistance in abscess fluid cultures was 40%; 13 cases of Klebsiella pneumoniae liver abscess were noted in our cohort, most of whom were Hispanic or Asian. CONCLUSIONS: PLA was principally managed by percutaneous drainage or aspiration with good outcomes. Further studies investigating the racial predilection of K. pneumoniae liver abscesses could reveal clues to its pathogenesis.

The relationship between the Hammett acidity and the decomposition of cefotaxime sodium in the solid state.

It was of interest to correlate the solid-state acidity to the decomposition of a model drug namely cefotaxime sodium. Amorphous samples containing either an indicator probe (thymol blue) or a model drug (cefotaxime sodium) were prepared by freeze-drying. The prepared samples were characterized using XRPD and Karl Fischer titrimetry. The acidity in the solid state was measured using reflectance spectroscopy. The kinetics of hydrolysis of cefotaxime sodium was studied in solid state at 50 °C in the Hammett acidity range of 8.12-8.61 and at constant ionic strength. The kinetics of decomposition of cefotaxime sodium in solution was also studied in basic media in the pH range of 7.9-8.9 at 50 °C and at constant ionic strength. The degradation was monitored using a validated HPLC method. The hydrolysis was found to follow pseudo-first-order kinetics in solution and solid state. The results obtained showed that there is a good correlation between the Hammett acidity function and the base-catalyzed decomposition of cefotaxime sodium in the solid state. The Hammett acidity-rate profile for cefotaxime decomposition is similar to the pH-rate profile obtained in solution. The decomposition of cefotaxime sodium in the solid state was found to be sensitive to the ionic strength.

Solid self-nanoemulsifying drug delivery system filled in enteric coated hard gelatin capsules for enhancing solubility and stability of omeprazole hydrochloride.

Omeprazole has poor water solubility, low stability in acidic solutions, and is subject to first pass metabolism resulting in low bioavailability. The objective was to enhance the dissolution and stability by preparing a solid-self nanoemulsifying drug delivery system (SNEDDS) and filling it in enteric coated HGCs. Drug solubility in many oils, surfactants, and cosurfactants was studied. Different SNEDDS were prepared and ternary phase diagrams were constructed. The optimum SNEDDS was evaluated. It was converted into solid by adsorption onto Neusilin® US2, and evaluated. Emulsions formed using Capryol 90, Cremophor RH 40, and ethanol formed spontaneously and were clear. Droplet size was 19.11 ± 3.11 nm, PDI was 0.18 ± 0.05, and zeta potential was -3.9 ± 1.56 mV. Non-medicated SNEDDS was thermodynamically stable. Cloud point was 88 ± 2 °C. Encapsulation efficiency and drug loading of solid-SNEDDS were 98.56 ± 0.44 and 1.29 ± 0.01%, respectively. Flow properties were much enhanced. Crystalline drug was adsorbed/precipitated onto Neusilin® US2 in amorphous form. Dissolution rate was enhanced as compared to commercial products and unprocessed drug. The drug was unstable at the accelerated stability conditions. Accordingly, the traditional stability study at 25 °C should be conducted. In conclusion, the solid-SNEDDS filled in enteric coated HGCs enhanced the dissolution rate and stability in acidic pH.

Cellulose Nanofiber Nanosheet Multilayers by the Langmuir-Blodgett Technique.

We describe a systematic approach for producing cellulose nanofiber (CNF) nanosheets using the Langmuir-Blodgett (LB) technique. The CNFs were obtained from sulfuric acid hydrolysis of commercially available microfibrillated cellulose. Needle-like CNFs, negatively charged by grafted sulfate groups, were maintained at the air-water interface, assisted by amphiphilic polymer, poly( N-dodecyl acrylamide) (pDDA). The CNFs produced a stable monolayer. The surface pressure increased steadily with a high collapse pressure of 50 mN m-1 when spread with formic acid and pDDA. The composite monolayers were transferred onto solid substrates as Y-type LB films using a vertical dipping method. Upstroke and downstroke transfer ratios of the films were, respectively, unity and 0.88, indicating that full coverage was achieved by the monolayer even for more than 200 layers. Results obtained using atomic force microscopy, Fourier transform infrared, and X-ray photoelectron spectroscopy showed that CNF nanosheets possess well-defined layer structures with average monolayer thickness of 5.3 nm. The relative amount of CNFs in the nanosheets was calculated as 62.6 wt % using the quartz crystal microbalance technique. The as-prepared nanosheets are optically transparent to visible light and have high hydrophobicity. In fact, the nanosheet transparency was higher than 88% at 600 nm wavelength for 24 layers. A miniscule amount of pDDA enables demonstration of free-standing CNF nanosheets with 1 cm width and 45.6 nm thickness (23 layers).

Revised Marshall Score: A New Approach to Stratifying the Severity of Acute Pancreatitis.

BACKGROUND: Modified Marshall Score is one of the severity scores for acute pancreatitis (AP) and is included in the Revised Atlanta Classification, but given its utilization of a set serum creatinine level (sCr), it may misclassify stable patients with chronic kidney disease (CKD) to a more severe class just due to their elevated sCr. AIMS: Our study aims to evaluate the role of CKD in AP and the possibility of utilizing acute kidney injury (AKI) into developing a new scoring system. METHODS: We retrospectively reviewed the electronic medical records of three hundred consecutive patients who were diagnosed with AP during hospitalization. Multiple demographic variables and clinical course indices were collected. Univariate logistic regression was then applied to predict mortality and ICU admission. Finally, receiver operating curve was utilized to compare original versus New Revised Marshall Score. RESULTS: Two hundred and eight-four (284) patients had a definitive diagnosis of AP. When comparing patients who had AKI on admission to those without AKI, the AKI group showed statistically significant higher mortality rate (5.6% vs. 1.1%, p = 0.04). Finally, we substituted the renal part of Marshall Score with our AKIN and we plotted the New "Revised" Marshall Score, which showed a higher AUROC compared to the original modified version (C-statistics 0.93 vs. 0.89, p < 0.05). CONCLUSION: We found that AKI predicts mortality and outperforms the use of a fixed sCr value alone. The use of our New Revised Marshall Score can accurately classify AP severity, avoiding misclassification of AP severity and providing better patient care.

Fluoxetine-induced Stevens-Johnson syndrome and liver injury.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced liver injuries (DILI) are overall rare and often associated with use of medications. Medications are also the most common aetiology of Stevens-Johnson syndrome (SJS), but SJS is seldom seen concomitantly with liver injury. Many common drugs can cause either one of these conditions; however, there are no reported cases of concomitant DILI and SJS secondary to fluoxetine. CASE SUMMARY: A 41-year-old female presented with a skin rash and abnormal liver function tests after the recent initiation of fluoxetine. Skin and liver biopsies showed features of SJS and DILI, respectively. Fluoxetine was stopped, following which there was improvement in her liver function tests and skin rash, without progression to fulminant hepatic failure. WHAT IS NEW AND CONCLUSION: Commonly used and safe pharmaceuticals such as fluoxetine have the potential for serious adverse events affecting the skin and liver.

Preparation and Characterization of an Oral Norethindrone Sustained Release/Controlled Release Nanoparticles Formulation Based on Chitosan.

Norethindrone has short half-life and low bioavailability. The objective was to prepare an oral Sustained Release/Controlled Release (SR/CR) Liquid Medicated Formulation (LMF) to enhance bioavailability and improve patient compliance. Norethindrone was solubilized in HP-ß-CD then complexed with different concentrations of Low Molecular Weight Chitosan (LMWC) (mucoadhesive). PolyElectrolyte Complexes (PECs) were homogenized with oleic acid using different concentrations of tween 80 to form LMFs (nanoemulsions). PECs and LMFs were characterized using different techniques. LMF 2 (optimum formula containing 2.5% w/v LMWC 11 kDa) was administered orally to dogs and mice for pharmacokinetic and adhesion evaluation. DSC, FTIR spectroscopy and SEM images indicated complex formation. Mean diameters of PECs were 183-425 nm, mean zeta potentials were + 18.6-+ 31 mV, and complexation efficiencies were 18.0-20.6%. Ten to fifteen percent tween was needed to prepare homogenous LMFs. Mean diameter of LMF 2 was 10.5 ± 0.57 nm, mean zeta potential was - 11.07 ± - 0.49 mV, encapsulation efficiency was 95.28 ± 1.75%, and each mL contained 145.5 µg norethindrone. SEM images showed spherical homogeneous oil droplets. All of these parameters were affected by molecular weight and concentration of chitosan. Norethindrone release from LMFs was controlled (zero order) for 96 h. It was little affected by molecular weight and concentration of chitosan but affected by concentration of tween 80. LMF 2 adhered to GIT for 48 h and enhanced the bioavailability. It showed no cytotoxicity after considering dilution in GIT and was stable for 3 months refrigerated. In conclusion an effective SR/CR LMF was prepared.

Desmoplastic Melanoma of the Periorbital Region.

Desmoplastic melanoma (DM) is a rare subtype of melanoma and an even smaller proportion of periocular melanomas. Here, the authors report 2 cases of DM in the periocular region. Staged according to the American Joint Committee on Cancer (AJCC) eighth edition classification, patient 1 presented with a stage IIIC (pT4apN1cM0) DM in the left lateral canthus with upper and lower eyelid and patient 2 presented with a stage IIIB (T4aN1bM0) DM in the left brow and supraorbital region with a parotid lymph node metastasis. In both patients, the lesions were amelanotic, with inflammatory appearance, and had been noted for several years before the correct diagnosis was made. In both patients, wide excision led to large surgical defects, and perineural invasion prompted adjuvant radiation therapy postoperatively. Patient 2 was treated with an immune checkpoint inhibitor for his parotid metastasis. Ophthalmologists should be aware of DM, its neurotrophic nature, and potential to metastasize with locally advanced lesions.