Disease Severity Scoring System Research Articles

Potential Usefulness of Lifetime Globotriaosylsphingosine Exposure at Diagnosis and Baseline Modified Disease Severity Score in Early-Diagnosed Patients With Fabry Disease.

Fabry disease (FD) is a lysosomal storage disease caused by a deficit of α-galactosidase A (GAL). Recently, plasma globotriaosylsphingosine (lyso-Gb3), a pathogenic analog of a substrate of GAL, has been suggested as a potential biomarker for FD, and disease severity scores, such as the Mainz Severity Score Index (MSSI), the Disease Severity Scoring System (DS3), and FASTEX (FAbry STabilization indEX), are useful tools for evaluating the severity of signs and symptoms in symptomatic FD patients. However, a more useful method of evaluating disease severity in early-diagnosed FD patients such as children, adult females, and asymptomatic patients is needed. Here, we proposed modified MSSI and DS3 scores to which we added phenotype, urinary mulberry bodies, and history of past pain attacksand examined the clinical usefulness of lyso-Gb3 and modified scores for early-diagnosed FD patients. In 13 early-diagnosed FD patients, we developed modified MSSI and DS3 scores and examined the correlation of lifetime lyso-Gb3 exposure at diagnosis with the conventional or modified scores.Lifetime lyso-Gb3 exposure was positively correlated only with the modified DS3 score. Additionally, we examined the long-term changes in plasma lyso-Gb3 concentration and in conventional MSSI, DS3, and FASTEX. In males, plasma lyso-Gb3 concentration decreased more rapidly than in females. In all patients, the severity scores were mild and remained nearly stable throughout the follow-up period. Our data suggest that lifetime lyso-Gb3 exposure and the modified DS3 score are useful in early-diagnosed patients.

Radiological and clinical evaluation of triple combination modulating therapy effectiveness in adult patients with cystic fibrosis

ObjectivesPrevious studies showed the clinical effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in cystic fibrosis (CF) patients and a recently published study evaluated twelve CF patients that performed chest and sinus computed tomography (CT) examinations and showed that ETI decreased pulmonary and sinus morphological abnormalities after one year of treatment. The aim of the present study was to evaluate the role of CFTR modulator therapy in improving radiological and clinical scores one year after ETI therapy initiation in a wider CF patient population. Materials and methodsBetween January 2020 and December 2022, 44 CF adult patients received elexacaftor-tezacaftor-ivacaftor (ETI) therapy for at least one year and underwent a chest CT examination at our hospital before and one year after ETI therapy initiation. Experienced radiologists who were blinded to the treatment assessed the images in consensus. The Brody-II score (BSII), the Lund-Mackay score (LM score) and the Sheikh-Lind CT sinus disease severity scoring system (SL score) were evaluated. Clinical scores such as cystic fibrosis clinical score (CFCS), Cystic Fibrosis Questionnaire-Revised (CFQ-R) score, the 22-item SinoNasal Outcome Test (SNOT-22) questionnaire and the CF-specific 28-modal abdominal symptom score (CFAbd-Score) were evaluated. Forced expiratory volume in 1 ​s (FEV1) and forced vital capacity (FVC) were also assessed. Paired samples t-tests were used to compare differences before and after one year of ETI therapy initiation, and Pearson's correlation coefficient was used to evaluate changes in FEV1 and total BSII and in FVC and total BSII. ResultsTotal BIIS one year after ETI initiation showed statistically significant lower scores (−6.0 p, p ​< ​0.0001). In particular, mucous plugging (−15.8 p, p ​< ​0.0001), peribronchial thickening (−16.2 p, p ​< ​0.0001) and parenchyma (−0.3 p, p ​= ​0.0397) showed statistically significant lower scores. LM score, SL score, FEV1, FVC, CFCS, CFQ-R, SNOT-22 and CFAbd-Score showed statistically significant lower scores one year after ETI initiation (p ​< ​0.0001). The correlation between ΔFEV1 and Δtotal BSII was statistically significant and moderate (r ​= ​−0.5188, p ​= ​0.0003), and the correlation between ΔFVC and Δtotal BSII was statistically significant and weak (r ​= ​−0.3160, p ​= ​0.0367). ConclusionEvolution of imaging findings on CT during follow-up closely correlate with improved clinical scores and functional data one year after ETI therapy initiation, indicating that CT may be a useful adjunct during follow-up of CF patients under this treatment as an objective measure of disease improvement.

Prediction of long-term mortality in patients with ischemic stroke based on clinical characteristics on the first day of ICU admission: An easy-to-use nomogram.

This study aimed to establish and validate an easy-to-use nomogram for predicting long-term mortality among ischemic stroke patients. All raw data were obtained from the Medical Information Mart for Intensive Care IV database. Clinical features associated with long-term mortality (1-year mortality) among ischemic stroke patients were identified using least absolute shrinkage and selection operator regression. Then, binary logistic regression was used to construct a nomogram, the discrimination of which was evaluated by the concordance index (C-index), integrated discrimination improvement (IDI), and net reclassification index (NRI). Finally, a calibration curve and decision curve analysis (DCA) were employed to study calibration and net clinical benefit, compared to the Glasgow Coma Scale (GCS) and the commonly used disease severity scoring system. Patients who were identified with ischemic stroke were randomly assigned into developing (n = 1,443) and verification (n = 646) cohorts. The following factors were associated with 1-year mortality among ischemic stroke patients, including age on ICU admission, marital status, underlying dementia, underlying malignant cancer, underlying metastatic solid tumor, heart rate, respiratory rate, oxygen saturation, white blood cells, anion gap, mannitol injection, invasive mechanical ventilation, and GCS. The construction of the nomogram was based on the abovementioned features. The C-index of the nomogram in the developing and verification cohorts was 0.820 and 0.816, respectively. Compared with GCS and the commonly used disease severity scoring system, the IDI and NRI of the constructed nomogram had a statistically positive improvement in predicting long-term mortality in both developing and verification cohorts (all with p < 0.001). The actual mortality was consistent with the predicted mortality in the developing (p = 0.862) and verification (p = 0.568) cohorts. Our nomogram exhibited greater net clinical benefit than GCS and the commonly used disease severity scoring system. This proposed nomogram has good performance in predicting long-term mortality among ischemic stroke patients.

A retrospective and comparative study between quick sequential organ failure assessment, CURB-65, and early warning scorings in COVID-19 patients to predict the disease severity and outcome

Background: Predicting the severity of COVID-19 infection in advance is the key to success of its treatment outcome. Various scoring systems are used to detect the severity of this disease but this study targets three simple scoring systems based on the vital parameters and basic routine laboratory tests. Aims and Objectives: The aim of the study was to assess the predictability of three scoring systems (Quick sequential organ failure assessment [q SOFA], CURB-65, and Early Warning scoring system) for disease severity at presentation in a rural-based tertiary care center. Materials and Methods: An observational, descriptive, retrospective, and cross-sectional study was conducted at Diamond Harbour Government Medical College Covid Hospital from January 2021 to January 2022 to assess the predictability of q SOFA, CURB-65, and Early Warning scoring system for disease severity at presentation. Results: The total number of participants was 561 among total admitted 1367 patients. A short descriptive analysis obtained from the variables to analyze the scorings howed among total sample collected, 57% were male and 43% were female. In this study, 87% of patients were survived and the rest 13% succumbed (death). There is no statistically significant difference in mortality between both genders. Age, pulse rate, and respiratory rate have a significant correlation with the outcome and altered sensorium is also highly associated with mortality. The accuracy was also found to be little higher for National Early Warning score (NEWS) score than CURB-65 scoring and q SOFA scoring (0.919, 0.914 and 0.907). Although all the scoring systems have high sensitivity (&gt;90%) (CURB 65: Most sensitive [0.99]), the specificities of all three scoring systems are below 50%. Among these three-scoring systems, NEWS showed the highest specificity (0.492) than q SOFA (0.423) and CURB 65 (0.394). Conclusion: We suggest NEWS score and CURB-65 as a better predictor for in-hospital mortality in COVID-19 patients as it is significantly sensitive and reasonably specific. It can be recommended in less equipped hospitals where only basic laboratory facilities are available. qSOFA can be utilized where no laboratory facility is available like in safe home and isolation centers.

Severity scoring system to guide transfusion management in pediatric non-deletional HbH.

Hemoglobin (Hb) H is generally recognized as mild thalassemia, despite its actual phenotypic diversity. A disease severity scoring system to guide initiation of regular transfusion among severely affected pediatric patients has not previously been reported. Patients with HbH were classified into transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) as a surrogate for disease severity. Alpha-globin genotypes and relevant clinical parameters associated with TDT were identified. Univariate and multiple logistic regression analyses were performed to yield the most suitable severity scoring system. From 246 patients with a median age of 14.3 (interquartile range 9.9-18.4) years initially enrolled into the study, the chance of having severe disease and developing TDT was remarkable only among patients with non-deletional HbH, for whom the scoring system was developed. Univariate and multiple logistic regression analyses resulted in three retained parameters associated with TDT, β-coefficients of which were used to develop the score. The final scoring system comprised age at diagnosis <2 years (score = 1), spleen size ≥3 cm (score = 1) and Hb at steady-state <7 (score = 4) or 7-8 g/dL (score = 3). A cutoff score ≥4 was associated with severe disease likely requiring regular transfusion (sensitivity 89.3%, specificity 81.4%), given regular transfusion resulted in maintained growth. The scoring system was validated in the second cohort of 77 non-deletional HbH, from which comparable sensitivity and specificity were obtained. The newly developed scoring system was practical and helpful to highlight severely affected pediatric non-deletional HbH patients with potential needs of regular transfusion. This can be used as a guide for optimal treatment and disease monitoring in the future.

Prognostic Indicators for the Early Prediction of Severe Dengue Infection: A Retrospective Study in a University Hospital in Thailand.

This study aimed to develop simple diagnostic guidelines which would be useful for the early detection of severe dengue infections. Retrospective data of patients with dengue infection were reviewed. Patients with diagnosed dengue infection were categorized in line with the International Statistical Classification of Diseases (ICD-10): A90, dengue fever; A91, dengue hemorrhagic fever; and A910, dengue hemorrhagic fever with shock. A total of 302 dengue-infected patients were enrolled, of which 136 (45%) were male and 166 (55%) were female. Multivariate analysis was conducted to determine independent diagnostic predictors of severe dengue infection and to convert simple diagnostic guidelines into a scoring system for disease severity. Coefficients for significant predictors of disease severity generated by ordinal multivariable logistic regression analysis were transformed into item scores. The derived total scores ranged from 0 to 38.6. The cut-off score for predicting dengue severity was higher than 14, with an area under the receiver operating curve (AUROC) of 0.902. The predicted positive value (PPV) was 68.7% and the negative predictive value (NPV) was 94.1%. Our study demonstrates that several diagnostic parameters can be effectively combined into a simple score sheet with predictive value for the severity evaluation of dengue infection.

Sinus Disease Grading on Computed Tomography Before and After Modulating Therapy in Adult Patients with Cystic Fibrosis.

Objectives:Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy effects on respiratory function, pulmonary exacerbations and quality of life have been well documented. However, CFTR modulator therapy effects on sinus disease have not been so well reported. A previous study reported that ivacaftor improves appearance of sinus disease on Computed Tomography (CT) in cystic fibrosis (CF) patients with G551D mutation. The aim of this study was to evaluate the effect of CFTR modulator therapy in sinus disease using CT scores in a wider CF patient population.Materials and Methods:Forty-eight adult patients with CF underwent at least one CT sinus examination before CFTR modulator therapy (ivacaftor, lumacaftor, ivacaftor/lumacaftor or elexcaftor/tezacaftor/ivacaftor) and one CT sinus examination one year after CFTR modulator therapy initiation. Two radiologists assessed the images in consensus. The Lund-Mackay score (LM score) and the Sheikh-Lind CT sinus disease severity scoring system (SL score) were used. The 22-item SinoNasal Outcome Test (SNOT-22) questionnaire was evaluated before CFTR modulator therapy and one year after CFTR modulator therapy initiation.Results:CT sinus examination after CFTR modulator therapy showed statistically significant lower mean LM, SL and SNOT-22 scores than CT sinus examination before CFTR modulator therapy (p < 0.001).Conclusion:Evolution of imaging findings on CT during follow-up closely correlate with improved SNOT-22 score one year after CFTR modulator therapy initiation, indicating that CT may be a useful adjunct during follow-up of CF patients under this treatment as an objective measure of sinonasal disease improvement.

New correlations between ocular parameters and disease severity in Spanish patients with Gaucher's disease Type I.

BackgroundGaucher’s disease is associated with a high variety of structural and functional abnormalities in the eye, which do not always affect visual acuity. The purpose of this study was to analyse ocular features in Spanish patients with Gaucher’s disease type I, and to investigate their possible correlation with phenotypic and burden parameters of this entity.MethodsThis cross-sectional observational study compared parameters belonging to 18 eyes from 9 Spanish patients with Gaucher’s disease Type I with 80 eyes from 40 healthy controls. Complete ophthalmological examination included choroidal and retinal thickness maps with swept source optical coherence tomography. Systemic analysis included genotype, plasmatic biomarkers, [ferritin, chemokine ligand 18 (CCL18) and chitotriosidase (ChT)] and severity scoring systems results [“Gaucher Disease Severity Score Index Type I" (GauSSI-I) and “Gaucher disease severity scoring system” (GD-DS3)].ResultsNine subjects (18 eyes) were cases (female: 55.5%, mean age 45 years; male: 44.5%, mean age 36 years) and 40 subjects (80 eyes) were controls (female: 49%, mean age 50 years; male: 51%, mean age 55 years). There were no statistically significant differences when comparing ocular parameters (visual acuity; axial length, refractive errors, corneal parameters, lens, retinal and choroidal thickness) between case and control subjects (p>0.05). A statistically significant moderate correlation was observed between lower retinal thickness and choroidal quadrants thickness and greater disease severity scores. A lower central retinal thickness also correlates with higher biological plasmatic levels, and has a statistically significant association with the most affected patient with genotype N370S/Del 55pb. Conversely, higher pachymetry involves a more severe plasmatic concentration of biomarkers.ConclusionsOur results suggest that pachymetry, and retinal and choroidal thickness, are associated with burden biomarkers and disease severity index scores in Spanish patients with Gaucher’s disease Type I.

IMPORTANCE OF NUTRITION ASSESSMENT IN CRITICALLY ILL PATIENTS

A timely assessment of nutritional status in critically ill patients is crucial. This was an observational prospective hospital study carried out for 3 months from December 2019 to February 2020 in an ICU in a multispecialty hospital in Madurai, Tamilnadu, India. All adult patients with ≥ 72 hours of ICU-LOS were included and their nutritional assessment was completed by SGA (Subjective Global Assessment) forms within 24 hours of ICU admission. Data collected regarding variables such as Age, Nutritional status, APACHE IV, SOFA score, presence of Comorbidities. All patients were studied about their duration of stay in ICU and hospital, Predicted Mortality rate, &amp; discharge outcome.120 patients were involved in the study in the age 62. 2 ± 14.years, among this 55.3% were males and rest 44.7% were females. Their complete nutritional assessment revealed that 50%, 43%, and 17% were well nourished, moderately malnourished, severely malnourished respectively. A strong correlation was observed between nutritional status, morbidity, and their prolonged stay in ICU. Mean ICU &amp; hospital mortality percentage was 37%, 45% respectively. The average duration of stay in the ICU and hospital was 13, 20 days respectively. Participants anthropometric data decreased considerably (mean weight, MUAC, calf circumference) during ICU discharge day. BMI comparison of admission and discharge didn’t show significant change. Timely nutrition intervention and medical nutrition therapy reduce the duration of patient stay in ICU and hospital and improved patient outcomes. The disease severity scoring system can be used as guidance for objective assessment of disease outcomes and estimation of the chance of recovery.

Treatment of Fabry Disease management with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS).

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL), resulting in the lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacological chaperone increasing endogenous AGAL activity. In this prospective observational multicentre study, safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under 'real-world' conditions. A total of 54 patients (26 females) (33 of these [61.1%] pre-treated with enzyme replacement therapy) with amenable mutations were analysed. Treatment was generally safe and well tolerated. A total of 153 events per 1000 patient-years were detected. Overall left ventricular mass index decreased after 24 months (all: -7.5 ± 17.4 g/m2, P = 0.0118; females: -4.6 ± 9.1 g/m2, P = 0.0554; males: -9.9 ± 22.2 g/m2, P = 0.0699). After 24 months, females and males presented with a moderate yearly loss of estimated glomerular filtration rate (-2.6 and -4.4 mL/min/1.73 m2 per year; P = 0.0317 and P = 0.0028, respectively). FD-specific manifestations/symptoms remained stable (all P > 0.05). A total of 76.9% of females and 50% of males suffered from pain, which has not improved under treatment. FD-specific disease scores (Disease Severity Scoring System and Mainz Severity Score Index) remained stable during treatment. AGAL activities and plasma lyso-Gb3 values remained stable, although some male patients presented with increasing lyso-Gb3 levels over time. Treatment with migalastat was generally safe and resulted in most patients in an amelioration of left ventricular mass. However, due to the heterogeneity of FD phenotypes, it is advisable that the treating physician monitors the clinical response regularly.

Characterization of COVID-19 Patients in an Intensive Care Unit

At the end of a new caused an epidemic of acute respiratory disease in Wuhan, China. The World Health Organization called this condition coronavirus disease 2019 and declared it pandemic on 11 March 2020. On that same date the first three COVID-19 cases were diagnosed in Cuba. The Acute Physiology and Chronic Health Evaluation II (APACHE II) is the disease severity scoring system most commonly used in ICUs. An observational descriptive prospective cohort study was carried out with the objective of describing the behavior of 20 SARS-CoV-2 positive cases in an intensive care unit. This was realized from March to July 2020 at the Intensive Care Unit of Dr Salvador Allende Clinical Surgical Hospital in Havana, Cuba. The study population was all the patients admitted for positive SARS-CoV-2 (n=20). Mean age was 64.35±15.21 years. Male sex prevailed. Mean hospital stay was 10.05±5.5 days. Mean APACHE II was 16.6±8.9. The prevailing symptoms were fever (55%), coughing (25%) and dyspnea (20%). Mortality of COVID-19 patients was associated to age, a longer stay in the intensive care unit, high APACHE II scores, reduced erythrosedimentation values and lymphocyte count. Hypertension was the most common pathological antecedent.

Rescue of autoimmune hepatitis by soluble MHC class II molecules in an altered concanavalin A-induced experimental model.

BackgroundSoluble major histocompatibility complex class II (sMHCII) molecules have been described to maintain tolerance through the suppression of autoreactive T lymphocytes. In order to evaluate their ability to rescue autoimmune hepatitis (AIH) symptoms, the present work attempted to administer sMHCII molecules to an in vitro as well as in vivo concanavalin A (ConA)‐induced AIH model.MethodsThe in vitro AIH model consisted of splenocyte stimulation with ConA in the presence or absence of serum‐isolated sMHCII molecules. An in vivo ConA‐modified model with or without sMHCII treatment was developed. The cytokine profile in culture supernatants and serum was tested by ELISA. Cell markers were evaluated by immunofluorescence, while cell proliferation by tritiated thymidine uptake. AIH symptoms were assessed by daily observations for the establishment of a disease severity scoring system and liver histology was evaluated using a biomolecular imager.ResultsThe presence of sMHCII molecules in the ConA‐stimulated cell cultures leads to a significant reduction of cell proliferation. The administration of sMHCII molecules to the ConA‐treated animals showed a significant reduction in the levels of IL‐2, IL‐4, and IL‐10, as well as a decrease in the number of spleen CD4+ and CD8+ cells. Upon development of a scoring system, it was shown that the sMHCII treatment was accompanied by a slower progression of the disease, while rescuing fibrotic liver morphology.ConclusionThe results presented in this study confirm the ability of sMHCII proteins to alleviate autoimmune hepatitis, possibly highlighting new therapeutic approaches for autoimmune diseases.

Risk Factors and Outcomes in Dogs With Respiratory Disease Undergoing Diagnostic Airway Lavage.

Advanced diagnostic testing is becoming increasingly important to accurately assess pulmonary parenchymal, airway, and pulmonary vascular diseases in dogs. Due to respiratory system compromise, diagnostic procedures performed under general anesthesia, including thoracic computed tomography (CT) and bronchoalveolar lavage (BAL), are thought to carry significant risk to dogs with respiratory disease. In lieu of performing these diagnostics, empirical medical therapy is often administered, potentially delaying appropriate therapy or providing unnecessary treatment. This study prospectively evaluated risk factors and outcomes for dogs with respiratory disease undergoing general anesthesia for thoracic CT and BAL. Arterial blood gas samples were taken pre- and post-BAL to evaluate pulmonary gas exchange. Pre-BAL arterial partial pressure of oxygen-to-fractional inspired oxygen ratio was used to stratify dogs into groups of mild or moderate to severe disease severity. A novel thoracic CT disease severity scoring system was used to independently stratify dogs into mild or moderate to severe groups. Statistical comparisons between groups were made for signalment, body weight, temperature, pulse, respiratory rate, WBC count, ventilator-acquired pulmonary mechanics (specific compliance and resistance), change in arterial partial pressure of oxygen post-BAL, and outcomes. Seventeen dogs were prospectively enrolled. A comparatively lower heart rate at presentation was the only potential marker of increased disease severity identified when stratified by CT severity score. Arterial partial pressure of oxygen did not significantly decrease post-BAL regardless of disease severity or stratification method. The CT scoring system significantly correlated with the pre-BAL arterial partial pressure of oxygen-to-fractional inspired oxygen ratio. Incidence of post-procedural complications was 18%, with all complications being transient. Mortality as a direct complication of diagnostics was 0%. When considering euthanasia secondary to severity of the underlying disease and poor prognosis or death due to unrelated disease, mortality was 18%. In dogs with respiratory disease undergoing advanced diagnostic procedures, the overall incidence of post-procedural morbidity was low with no mortality directly attributed to the procedures. A novel CT disease severity scoring system was utilized and shows promise as a tool for evaluation of disease severity in this patient population when compared to arterial blood gas analysis.

A scoping review to identify and map the multidimensional domains of pain in adults with advanced liver disease

ABSTRACT Background: Pain is a significant problem in adults living with advanced liver disease, having limited guidance available for its clinical management. While pain is considered a multidimensional experience, there have been limited reviews of the pain literature in advanced liver disease conducted with a multidimensional framework. Aims: The goal of this scoping review was to identify and map the multidimensional domains of pain in adults with advanced liver disease using the biopsychosocial model. Methods: We used Arksey and O’Malley’s scoping framework. A search was conducted in MEDLINE, Embase, AMED, and CINAHL databases and the gray literature using specific eligibility criteria (1990–2019). Citation selection and data extraction were performed by two independent reviewers and in duplicate. Results: Of the 43 studies that met inclusion criteria, 51% were from North America and 93% utilized quantitative methods. The combined studies reported on 168,110 participants with ages ranging between 23 to 87 years. Only 9% reported an objective scoring system for liver disease severity. Few studies reported pain classification (9%) and intensity (16%). Pain prevalence ranged between 18% and 100%, with pain locations including joint, abdomen, back, head/neck, and upper/lower extremities. We identified and mapped 115 pain factors to the biopsychosocial model: physical (81%), psychological (65%), and sociocultural (5%). Only 9% measured pain using validated multidimensional tools. Pharmacological intervention (92%) prevailed among pain treatments. Conclusions: Pain is not well understood in patients with advanced liver disease, having limited multidimensional pain assessment and treatment approaches. There is a need to systematically examine the multidimensional nature of pain in this population.

FAbry STabilization indEX (FASTEX): Clinical evaluation of disease progression in Fabry patients

BackgroundTwo established scores, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), quantify the disease burden in Fabry disease (FD), while the recent developed FAbry STabilization indEX (FASTEX) aims to detect disease progression. ObjectiveMSSI, DS3 and FASTEX were compared to evaluate disease stability or progression in a prospective cohort of Fabry patients under enzyme replacement therapy (ERT). MethodsDisease load of 62 patients (28 [45%] females) treated with ERT (26 [42%] under agalsidase-alfa) was assessed using the current scores and re-assessed after 12 months of treatment. Fifteen (24%) patients were ERT-naïve at baseline. ResultsAll scores showed a correlation with each other, while MSSI and DS3 showed the strongest (Pearson r: 0.81, p < .0001). Plasma lyso-Gb3 levels in naïve patients correlated with increasing DS3 and MSSI scores (Pearson r: 0.60, p < .05; Pearson r: 0.64, p < .01; respectively), but not with the total weighted FASTEX score. Longitudinal analysis suggested a stable disease course using DS3 and MSSI. Only males long-term-treated with agalsidase-alfa presented with a slight increase of the general MSSI score (p = .0084). By contrast, the FASTEX score demonstrates that only 21 patients (33.9%) were stable, all other patients presented a disease progression. Patients with an unstable FASTEX mainly suffered from a significant loss of renal function (eGFRcreat: −2.7 ± 7.3 ml/min/1.73 m2, p = .0298). ConclusionWe conclude that the FASTEX seems to be a simple and user friendly, valuable tool to assess early changes in disease progression even in smaller patient cohorts and short term surveillance.

Correlation Between MELD and UNa/K Ratio in Predicting Renal Dysfunction in Cirrhotic Patients.

BackgroundRenal dysfunction is one of the dreaded complications of cirrhosis. MELD is a validated chronic liver disease (CLD) severity scoring system. Urinary (U) Na/K ratio closely correlates with renal dysfunction in terms of low GFR in cirrhotic patients.Patients and MethodsAll consecutive patients with decompensated cirrhosis between the age of 18 to 70 years, of either gender, presenting in the outpatients’ department of Sindh Institute of Urology and Transplantation, Karachi, from June 2015 to June 2017 were included. The MELD score was calculated and the UNa/K ratio less than 1 was taken as surrogate marker of renal dysfunction. Statistical analysis was performed by SPSS (version 20.0).ResultsA total of 71 patients were enrolled. The mean age was 43.79 years and majority were male (67.6%). The most common cause of liver cirrhosis was HCV, found in 42 (59.2%) patients. The mean CTP score was 10.48 ± 2.069 (range: 6–14) with majority of the patients following in class C, that is, 48 (67.6%). Mean MELD score was 21.75 ± 8.96 (range: 8–43). In 57 patients (80.3%), MELD score was > 15.The mean serum creatinine and mean serum sodium were 1.5 ± 1.1 mg/dl (range: 0.37–5.3) and 133.79 ± 6.9 mmol/L (range: 112–152), respectively. Mean urinary sodium and urinary potassium were 38.60 ± 46.64 mmol/L (range: 5–181) and 38.15 ± 23.9 mmol/L (range: 4.3–112), respectively. In majority of study population, UNa/K ratio was below 1, that is, in 52 patients (73.2%). Statistically significant correlation was documented between MELD score and UNa/K ratio (ɤ = 0.34, P = 0.004).ConclusionThe inverse correlation between MELD scores and UNa/K ratio indicates that patients with CLD and higher MELD scores might have renal dysfunction. This finding however should be corroborated by large scale studies.

Overview and update on biologic therapy for moderate-to-severe hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a frequently devastating inflammatory skin disorder. Although many treatments have been tried and tested to date, there is only one Food and Drug Administration-approved treatment option, adalimumab, which is currently indicated for moderateto- severe HS. Our understanding of the management of HS with biologic agents and with nonantibiotic and/ or antimicrobial systemic therapies continues to evolve. In this article, we summarize the existing data on biologics and other small-molecule systemic agents, as well as share our personal experiences with the pharmacological management of HS in the clinical setting. Continued challenges that limit our ability to study and treat this disease effectively include a lack of a universally employed scoring system for disease severity, high variability in clinical presentation, high cost of off-label therapy, and the scarcity of long-term studies on treatment response and medication safety.

Disease severity scoring system for acid sphingomyelinase deficiency: Severity score domains and components

Fabry disease, a rare, X-linked lysosomal storage disease, arises from deficiency of the lysosomal hydrolase, α-galactosidase A (GLA) which disrupts the catabolism of globo- series glycosphingolipids (GSLs). One potential link between GLA deficiency and vascular dysfunction may be changes in endothelial nitric oxide synthase (eNOS) function. GLA-deficient EA.hy926 cells were obtained by siRNA knockdown of GLA expression and by mutation of GLA with CRISPR/Cas9 gene editing to investigate the effects of GLA deficiency on eNOS. As previously observed with siRNA knockdown of GLA, globotriaosylceramide (Gb3) accumulated in EA.hy926 cells. In contrast, Gb3 did not accumulate in CRISPR/Cas9 gene edited GLA-deficient cells, but instead, globotetraosylceramide (Gb4). However, in both the siRNA and CRISPR/Cas9 models globotriaosylsphingosine (lyso-Gb3) was elevated. As was previously observed with siRNA knockdown of GLA expression, CRISPR/Cas9 GLA-deficient cells had lower eNOS activity. Restoring GLA activity in GLA-deficient cells with exogenous GLA treatment improved eNOS activity. In contrast, treating cells with the glucosylceramide synthase inhibitor, eliglustat, decreased NOS activity. These results suggest that eNOS uncoupling is due to GLA deficiency, and not necessarily due to elevated Gb3 per se. It was observed that lyso-Gb3 inhibits eNOS activity.

Correlating liver stiffness with disease severity scoring system (DS3) values in Gaucher disease type 1 (GD1) patients

Gaucher disease (GD) is an autosomal-recessive lysosomal storage disease caused by a deficiency of the enzyme, glucocerebrocidase, resulting in accumulation of lipid-laden storage cells in multiple organs such as bone marrow, liver, spleen, and lungs. Type 1 Gaucher disease is the most common form of this condition in which the brain and spinal cord (the central nervous system) are not affected. The Gaucher disease severity scoring system (GD-DS3) is typically used to assess disease severity accounting for skeletal, hematologic, and visceral disease. In addition to being time consuming for the clinician to calculate the scores, some of the assessments are subjective and may falsely increase or decrease disease severity. The purpose of this study was to determine if there is a correlation between liver stiffness values obtained from MR elastography (MRE) and the GD-DS3 score.An IRB approved, HIPAA compliant retrospective study was performed. All patients with type 1 GD imaged with MRE between 2011 and 2016 were included in this study. Clinical and imaging data was collected. Two pediatric radiologists analyzed MR images from abdomen and thigh studies independently to determine bone marrow involvement using a semi-quantitative scoring system with one reviewer analyzing a subset of studies to determine inter-observer reliability. The collected data was used to calculate a GD-DS3 score for all patients. GD-DS3 scores were compared with liver MRE stiffness values.Clinical MRE scores were plotted against GD-DS3 severity scores for 31 patients (15 males, 16 females; median age 27years, age range: 4–67years). The median GD-DS3 score was 4 (range: 1–10.1) and median MRE value was 2.43kPa (range: 1.30–5.20kPa). A significant positive correlation was found between MRE and GD-DS3 scores; Pearson's correlation coefficient value of r=0.47, p<0.001 for all scores, r=0.68, p<0.001 for complete scores and r=0.46, p<0.07 for incomplete scores. The inter-observer variation of bone marrow burden showed only fair agreement with a Kappa coefficient of 0.26.There is a significant positive correlation between increasing liver stiffness and increasing composite GD-DS3 scores. This supports the use of MRE, a non-invasive reproducible quantitative test, as both an additional assessment and independent marker for monitoring disease severity and progression in GD.

A study on the efficacy of APACHE-IV for predicting mortality and length of stay in an intensive care unit in Iran

Background: Clinical assessment of disease severity is an important part of medical practice for prediction of mortality and morbidity in Intensive Care Unit (ICU). A disease severity scoring system can be used as guidance for clinicians for objective assessment of disease outcomes and estimation of the chance of recovery. This study aimed to evaluate the hypothesis that the mortality and length of stay in emergency ICUs predicted by APACHE-IV is different to the real rates of mortality and length of stay observed in our emergency ICU in Iran. Methods: This was a retrospective cohort study conducted on the data of 839 consecutive patients admitted to the emergency ICU of Nemazi Hospital, Shiraz, Iran, during 2012-2015. The relevant variables were used to calculate APACHE-IV. Length of stay and death or discharge, Glasgow coma score, and acute physiology score were also evaluated. Moreover, the accuracy of APACHE-IV for mortality was assessed using area under the Receiver Operator Characteristic (ROC) curve. Results: Of the studied patients, 157 died and 682 were discharged (non-survivors and survivors, respectively). The length of stay in the ICU was 10.98±14.60, 10.22 ± 14.21 and 14.30±15.80 days for all patients, survivors, and non-survivors, respectively. The results showed that APACHE-IV model underestimated length of stay in our emergency ICU (p<0.001). In addition, the overall observed mortality was 17.8%, while the predicted mortality by APACHE-IV model was 21%. Therefore, there was an overestimation of predicted mortality by APACHE-IV model, with an absolute difference of 3.2% (p=0.036). Conclusion: The findings showed that APACHE-IV was a poor predictor of length of stay and mortality rate in emergency ICU. Therefore, specific models based on big sample sizes of Iranian patients are required to improve accuracy of predictions.