New onset inflammatory bowel disease in patient treated with secukinumab: Case report and review of literature.

Psoriasis is a chronic autoimmune skin disorder that can vary in severity and extent of disease. While localized disease can be managed with topical medications, widespread disease often requires systemic therapy including biologics. This medication class targets different components of the immune system and thus modulates disease activity. The biologic secukinumab is a human monoclonal antibody against interleukin-17A used for the treatment of psoriasis and psoriatic arthritis; cases of inflammatory bowel disease (IBD) have been observed in clinical trials to be associated with this medication. This review aims to provide evidence for the relationships between secukinumab treatment and the development of IBD. We have examined review articles and original research papers, published between 2010 and 2020, using the following keywords: psoriasis, psoriatic arthritis, secukinumab, IBD, Crohn's disease, ulcerative colitis, interleukin-17, IL-17, IL-17 inhibitor. Case reports have noted an association between secukinumab use and IBD and have called for IBD pre-screening in patients who will be prescribed this medication. Clinical trials concluded that secukinumab was associated with IBD, while retrospective studies have had mixed results, with most studies showing no statistical significance between secukinumab and IBD but having seen patients with history of IBD or family histories experience new-onset IBD or flare-ups. Given the utilization of secukinumab as a therapy for psoriasis and psoriatic arthritis, appropriate screening and risk stratification could help limit morbidity and mortality that can be associated with secukinumab-induced IBD.

E-Consults in Dermatology: A Retrospective Analysis.

Dermatology electronic consultations (e-consults) placed by primary care providers (PCPs) can increase access to specialty care while reducing wait times and providing accurate clinical outcomes. These e-consults also may reduce barriers for underserved patients who historically have limited access to dermatologic care. Our retrospective chart review examines patient outcomes from a dermatology e-consult program at a tertiary care medical center. E-consults effectively increased access to dermatology care while shortening wait times and reducing health care expenditures.

Tumid lupus erythematosus and systemic lupus erythematosus: a rare coexistence.

A patient diagnosed with tumid lupus erythematosus (TLE) was subsequently found to have systemic lupus erythematosus (SLE) after presenting to a tertiary care medical centre with shortness of breath and oedema. In this commentary, we discuss this patient's presentation and the association between TLE and SLE.

Long-acting phosphodiesterase-5 inhibitor, tadalafil, induces sustained cardioprotection against lethal ischemic injury.

The ability of pharmacological preconditioning mimetics to confer long-lasting and sustained cardioprotection may be a logical criterion to develop a drug that can be used clinically for cardioprotection. We propose here that the use of long-acting phosphodiesterase-5 inhibitor, tadalafil, may confer sustained cardioprotection against ischemia. Tadalafil (5 mg/kg) was administered orally to male C57B/6J mice (n = 6 in each treatment subgroup at each time point studied). Hearts were isolated and subjected to 40 min of ischemia and 30 min of reperfusion on Langendorff's apparatus at 1, 12, 24, 36, 48, 60, 72, and 108 h after tadalafil administration. In 1- to 48-h subgroups, tadalafil was given once at 0 h only. In 60- and 72-h subgroups, tadalafil was given twice at 0 and 36 h. Similarly, in the 108-h subgroup, tadalafil was administered at 0, 36, and 72 h. In the same subgroups, wortmannin (15 microg/kg ip), an inhibitor of phosphatidylinositol 3-kinase or 5-hydroxydecanoic acid (5 mg/kg ip), an inhibitor of mitochondrial ATP-sensitive K(+) channels, was given together with tadalafil, and the hearts were subjected to ischemia-reperfusion at 36 h to determine whether the effect of tadalafil on ischemia-reperfusion injury was abolished. As a result, tadalafil treatment reduced left ventricular end-diastolic pressure and increased left ventricular developed pressure as well as reduced lactate dehydrogenase release. This protection remained till 36-40 h, and thereafter it vanished. The readministration of tadalafil at 36 and 72 h restored the protection till 108 h. Tadalafil treatment accelerated Akt phosphorylation in cardiac tissue and decreased myocyte apoptosis. The administration of wortmannin abolished the beneficial effects of tadalafil on hemodynamic parameters and myocyte apoptosis, together with significantly reduced Akt phosphorylation. 5-Hydroxydecanoic acid also abolished the antiapoptotic effect of tadalafil. It is concluded that tadalafil treatment induces the long-term protection of ischemic myocardium via phosphatidylinositol 3-kinase/Akt signaling pathway.

General practitioner's knowledge regarding the diagnosis and drug therapy for acute myocardial infarction.

OBJECTIVE: To assess the general practitioners (GP) knowledge regarding the diagnosis and initial drug therapy for acute myocardial infarction (AMI). METHODS: A questionnaire-based survey was conducted in randomly selected GPs of Karachi. Doctors working in community as GPs who were registered medical practitioners having a Bachelor of Medicine & Bachelor of Surgery degree were included in the study. Doctors working at tertiary care facilities or having a post graduate degree or post graduate training in a specialty other than family medicine were excluded from the study. RESULTS: A total of 186 GPs participated in our study. GPs who studied research journals were 2.33 times more likely to investigate serum cardiac troponins levels for the diagnosis of AMI compared to those who did not study research journals (P = 0.02). Twenty six percent of the GPs said that they would refer a patient with suspected AMI without treatment, while 76% said that they would consider some treatment prior to referral. Fifty eight percent of the GPs identified ST segment elevation myocardial infarction (STEMI) of < 12 hours duration as an indication of thrombolysis while 28% identified posterior wall AMI as a thrombolytic indication. CONCLUSION: GPs, although adequately aware of the presenting features of AMI, were lacking in knowledge regarding the means for confirmation of diagnosis, initial drug therapy and were less likely to carry management steps in their practice.

Outcomes in culture positive and culture negative ascitic fluid infection in patients with viral cirrhosis: cohort study.

BACKGROUND: Ascitic fluid infection (AFI) in cirrhotic patients has a high morbidity and mortality. It has two variants namely, spontaneous bacterial peritonitis (SBP) and culture negative neutrocytic ascites (CNNA). The aim of this study was to determine the outcome in cirrhotic patients with culture positive (SBP) and culture negative neutrocytic ascites. METHODS: We analyzed 675 consecutive hepatitis B and/or C related cirrhosis patients with ascites admitted in our hospital from November 2005 to December 2007. Of these, 187 patients had AFI; clinical and laboratory parameters of these patients including causes of cirrhosis, Child Turcotte Pugh (CTP) score were recorded. RESULTS: Out of 187 patients with AFI, 44 (23.5%) had SBP while 143 (76.4%) had CNNA. Hepatitis C virus (HCV) infection was the most common cause of cirrhosis in 139 (74.3%) patients. Patients with SBP had high CTP score as compared to CNNA (12.52 +/- 1.45 vs. 11.44 +/- 1.66); p < 0.001. Platelets count was low in patients with SBP (101 +/- 53 x 10(9)/L) as compared to CNNA (132 +/- 91 x 10(9)/L), p = 0.005. We found a high creatinine (mg/dl) (1.95 +/- 1.0 vs. 1.44 +/- 0.85), (p = 0.003) and high prothrombin time (PT) in seconds (24.8 +/- 6.6 vs. 22.4 +/- 7.2) (p = 0.04) in SBP as compared to CNNA. More patients with SBP (14/44; 31.8%) had blood culture positivity as compare to CNNA (14/143; 9.8%), p = 0.002. Escherichia. Coli was the commonest organism in blood culture in 15/28 (53.5%) patients. SBP group had a higher mortality (11/44; 25%) as compared to CNNA (12/143; 8.4%), p = 0.003. On multiple logistic regression analysis, creatinine >1.1 mg/dl and positive blood culture were the independent predictors of mortality in patients with SBP. CONCLUSION: Patients with SBP have a higher mortality than CNNA. Independent predictors of mortality in SBP are raised serum creatinine and a positive blood culture.

Cardiac Progenitors Induced from Human Induced Pluripotent Stem Cells with Cardiogenic Small Molecule Effectively Regenerate Infarcted Hearts and Attenuate Fibrosis.

Cardiac progenitor cells (CPCs) being multipotent offer a promising source for cardiac repair due to their ability to proliferate and multiply into cardiac lineage cells. Here, we explored a novel strategy for human CPCs generation from human induced pluripotent stem cells (hiPSCs) using a cardiogenic small molecule, isoxazole (ISX-9) and their ability to grow in the scar tissue for functional improvement in the infarcted myocardium. CPCs were induced from hiPSCs with ISX-9. CPCs were characterized by immunocytochemistry and RT-PCR. The CPC survival and differentiation in the infarcted hearts were determined by in vivo transplantation in immunodeficient mice following left anterior descending artery ligation and their effects were determined on fibrosis and functional improvement. ISX-9 simultaneously induced expression of cardiac transcription factors, NK2 homeobox 5, islet-1, GATA binding protein 4, myocyte enhancer factor-2 in hiPSCs within 3 days of treatment and successfully differentiated into three cardiac lineages in vitro. Messenger RNA and microRNA-sequencing results showed that ISX-9 targeted multiple cardiac differentiation, proliferation signaling pathways and upregulated myogenesis and cardiac hypertrophy related-microRNA. ISX-9 activated multiple pathways including transforming growth factor ß induced epithelial-mesenchymal transition signaling, canonical, and non-canonical Wnt signaling at different stages of cardiac differentiation. CPCs transplantation promoted myoangiogenesis, attenuated fibrosis, and led to functional improvement in treated mice.

Evaluation of immune response to Hepatitis B vaccine in health care workers at a tertiary care hospital in Pakistan: an observational prospective study.

BACKGROUND: Seroconversion rates reported after Hepatitis B virus (HBV) vaccination globally ranges from 85-90%. Health care workers (HCWs) are at high risk of acquiring HBV and non responders' rates after HBV vaccination were not reported previously in Pakistani HCWs. Therefore we evaluated immune response to HBV vaccine in HCWs at a tertiary care hospital in Karachi, Pakistan. METHODS: Descriptive observational study conducted at Aga Khan University from April 2003 to July 2004. Newly HBV vaccinated HCWs were evaluated for immune response by measuring serum Hepatitis B surface antibody (HBsAb) levels, 6 weeks post vaccination. RESULTS: Initially 666 employees were included in the study. 14 participants were excluded due to incomplete records. 271 (41%) participants were females and 381(59%) were males. Majority of the participants were young (<25-39 years old), regardless of gender. Out of 652 HCWs, 90 (14%) remained seronegative after six weeks of post vaccination. The percentage of non responders increased gradually from 9% in participants of <25, 13% in 25-34, 26% in 35-49, and 63% in >50 years of age. Male non responders were more frequent (18%) than female (8%). CONCLUSION: Seroconversion rate after HBV vaccination in Pakistani HCWs was similar to that reported in western and neighboring population. HCWs with reduced immune response to HBV vaccine in a high disease prevalent population are at great risk. Therefore, it is crucial to check post vaccination HBsAb in all HCWs. This strategy will ensure safety at work by reducing nosocomial transmission and will have a cost effective impact at an individual as well as at national level, which is very much desired in a resource limited country.

Hyperuricemia: An Early Marker for Severity of Illness in Sepsis.

Background. Uric acid can acutely activate various inflammatory transcription factors. Since high levels of oxyradicals and lower antioxidant levels in septic patients are believed to result in multiorgan failure, uric acid levels could be used as a marker of oxidative stress and poor prognosis in patients with sepsis. Design. We conducted a prospective cohort study on Medical Intensive Care Unit (MICU) patients and hypothesized that elevated uric acid in patients with sepsis is predictive of greater morbidity. The primary end point was the correlation between hyperuricemia and the morbidity rate. Secondary end points were Acute Kidney Injury (AKI), mortality, Acute Respiratory Distress Syndrome (ARDS), and duration of stay. Results. We enrolled 144 patients. 54 (37.5%) had the primary end point of hyperuricemia. The overall morbidity rate was 85.2%. The probability of having hyperuricemia along with AKI was 68.5% and without AKI was 31.5%. Meanwhile the probability of having a uric acid value <7 mg/dL along with AKI was 18.9% and without AKI was 81.1% (p value < 0.0001). Conclusion. We report that elevated uric acid levels on arrival to the MICU in patients with sepsis are associated with poor prognosis. These patients are at an increased risk for AKI and ARDS.

Timing of tracheotomy in mechanically ventilated critically ill morbidly obese patients.

Background. The optimal timing of tracheotomy and its impact on weaning from mechanical ventilation in critically ill morbidly obese patients remain controversial. Methods. We conducted a retrospective chart review of morbidly obese subjects (BMI ≥ 40 kg/m(2) or BMI ≥ 35 kg/m(2) and one or more comorbid conditions) who underwent a tracheotomy between July 2008 and June 2013 at a medical intensive care unit (ICU). Clinical characteristics, rates of nosocomial pneumonia (NP), weaning from mechanical ventilation (MV), and mortality rates were analyzed. Results. A total of 102 subjects (42 men and 60 women) were included; their mean age and BMI were 56.3 ± 15.1 years and 53.3 ± 13.6 kg/m(2), respectively. There was no difference in the rate of NP between groups stratified by successful weaning from MV (P = 0.43). Mortality was significantly higher in those who failed to wean (P = 0.02). A cutoff value of 9 days for the time to tracheotomy provided the best balanced sensitivity (72%) and specificity (59.8%) for predicting NP onset. Rates of NP and total duration of MV were significantly higher in those who had tracheostomy ≥ 9 days (P = 0.004 and P = 0.002, resp.). Conclusions. The study suggests that tracheotomy in morbidly obese subjects performed within the first 9 days may reduce MV and decrease NP but may not affect hospital mortality.