Biliary Atresia Animal Models: Is the Needle in a Haystack?

Biliary atresia (BA) is a progressive fibro-obliterative process with a variable degree of inflammation involving the hepatobiliary system. Its consequences are incalculable for the patients, the affected families, relatives, and the healthcare system. Scientific communities have identified a rate of about 1 case per 10,000-20,000 live births, but the percentage may be higher, considering the late diagnoses. The etiology is heterogeneous. BA, which is considered in half of the causes leading to orthotopic liver transplantation, occurs in primates and non-primates. To consolidate any model, (1) more transport and cell membrane studies are needed to identify the exact mechanism of noxa-related hepatotoxicity; (2) an online platform may be key to share data from pilot projects and new techniques; and (3) the introduction of differentially expressed genes may be useful in investigating the liver metabolism to target the most intricate bilio-toxic effects of pharmaceutical drugs and toxins. As a challenge, such methodologies are still limited to very few centers, making the identification of highly functional animal models like finding a "needle in a haystack". This review compiles models from the haystack and hopes that a combinatorial search will eventually be the root for a successful pathway.

Delirium Tremens Leads to Poor Outcomes for Acute Coronary Syndrome.

OBJECTIVES: The mortality rate for patients with delirium tremens (DT) is 5%. As these patients present with elevated cardiac indices, coexisting DT in acute coronary syndrome (ACS) likely worsens outcomes. Our aim was to examine the outcomes of alcohol withdrawal syndrome (AWS) and DT in patients with ACS. METHODS: We used the Nationwide Inpatient Sample (2000-2009) for our study. A multivariable logistic regression model was used to examine the independent association of AWS on inhospital mortality and a multivariable linear regression was used to examine the effect of AWS on inpatient length of stay (LOS). RESULTS: An estimated 2,465,852 admissions with a primary diagnosis of ACS were analyzed. Of these, 4,499 patients had AWS and 3,460 patients had DT. Adjusting for age, gender, race, insurance, hospital characteristics, Charlson's comorbidity index, stent placement and year, the inhospital mortality was significant only for DT (OR 1.56; 95% CI 1.21-2.04). Inpatient LOS was 1.64 (95% CI 1.58-1.73) times higher in those with AWS and 2.33 (95% CI 2.22-2.43) times higher in DT when compared to nonalcoholics. Total hospital charges were higher for patients with AWS and DT when compared to nonalcoholics. CONCLUSIONS: Coexisting DT in ACS admissions is associated with increased mortality along with longer inpatient LOS and higher hospital costs.

Varicose vein trauma: a risk for pulmonary embolism.

Pulmonary embolism (PE) is a deceptive condition which is often incorrectly diagnosed leading to high morbidity and mortality. We present a case where symptoms were localised to different areas of the body starting with post-traumatic pain over lower extremity varicosities that migrated sequentially over a month to the knee, hip, back, abdomen and chest finally presenting as syncope. Despite a low pre-test clinical probability, a very high index of suspicion led to a timely diagnosis of a massive bilateral PE that eventually caused a troponin leak. The aetiology is highly suspicious of a thrombus which originated in the veins of the leg due to trauma over varicose veins.The case described here exemplifies the importance of considering trauma to varicosities as a risk factor for embolism when the clinical picture is concerning but other signs and symptoms of PE are not apparent.

Dose adjustment of carboplatin in patients on peritoneal dialysis.

The Calvert equation has been extensively used to determine the dosage of carboplatin. However, in patients on dialysis, it predicts the same dosage regardless of the frequency of dialysis. Clearance of carboplatin during hemodialysis has been studied to a lesser extent, but there have been very few studies which have investigated the clearance of carboplatin in patients on peritoneal dialysis. A mathematical formula is proposed here to predict the dose of carboplatin for a given AUC in patients on peritoneal dialysis. This formula takes into account the frequency of dialysis sessions and the time delay between carboplatin infusion and the initiation of dialysis. The formula predicts an approximately similar dosage of carboplatin as that of the Calvert formula in patients undergoing peritoneal dialysis four times per day if dialysis is initiated 12 h after infusion. The formula may help in guiding the adjustment of carboplatin dose in patients who receive a lesser number of dialysis sessions per day and in those patients whose dialysis is initiated at different times (0-24 h) after carboplatin infusion. It is suggested that usage of this formula will result in a better dosage of carboplatin to suit specific dialysis frequencies in specific patients and eventually may result in a better efficacy and toxicity profile.

Giant adrenal myelolipoma masquerading as heart failure.

Adrenal myelolipomas are rare benign tumors of the adrenal cortex composed of adipose and hematopoietic cells. They have been postulated to arise from repeated stimulation by stress, inflammation and ACTH oversecretion. Myelolipomas are usually detected incidentally on imaging and do not require any active intervention besides regular follow-up by imaging. However, myelolipomas may insidiously grow to large sizes and cause mass effects and hemorrhage. Timely diagnosis and surgical resection are curative and lifesaving.

Dose adjustment of carboplatin in patients on hemodialysis.

Carboplatin is one of the most prescribed cytotoxic drug, which is extensively used in the treatment regimens of several malignancies. The therapeutic efficiency of carboplatin has been found to correlate the area under curve (AUC). The Calvert formula has been extensively used to determine the dose of carboplatin for a fixed AUC and glomerular filtration rate (GFR). This formula has also been used in patients with end-stage renal disease on hemodialysis by assuming that the GFR is zero. This is applicable to patients who receive hemodialysis within 12-18 h after carboplatin infusion. After the first 24 h, a majority of the carboplatin is bound to proteins is not easily dialyzable and hence continues to remain in the blood stream despite repeated sessions of hemodialysis. We derive a correction factor to calculate the resultant AUC in such patients. The analysis done by using this correction factor shows that the AUC can increase by eightfold in patients who received the adjusted dose but whose hemodialysis was delayed beyond 24 h after infusion. The correction factor proposed here can also be used to calculate the dose adjustment required a priori in patients who may receive delayed hemodialysis. It is also useful to predict the AUC and estimate the resultant toxicity in such patients.

Renal medullary cancer in a patient with sickle cell trait.

Renal medullary cancer is a rare malignancy almost exclusively seen in young patients of African ethnicity. These patients often present with the cardinal symptoms of hematuria, flank pain, and an abdominal mass, and this malignancy has been associated with patients carrying sickle cell trait. It is estimated that 300 million people worldwide carry sickle cell trait, and the presence of hematuria in these patients should be treated as a harbinger of a possible malignancy. Notably, this tumor mostly develops on the right side of the body. Patients often present with it at an advanced stage and the prognosis is poor. Therefore, a high index of suspicion in a patient of African descent presenting with a right sided abdominal mass and hematuria may assist in an early diagnosis. Current chemotherapy options are very limited, and early detection may provide a chance for surgical resection. It may also provide a bigger time frame for the initiation of novel chemotherapy regimens in patients who fail current chemotherapy regimens.

Identifying oncological emergencies.

Prompt identification and treatment of life-threatening oncological conditions is of utmost importance and should always be included in the differential diagnosis. Oncological emergencies can have a myriad of presentations ranging from mechanical obstruction due to tumor growth to metabolic conditions due to abnormal secretions from the tumor. Notably, hematologic and infectious conditions may complicate the presentation of oncological emergencies. Advanced testing and imaging is generally required to recognize these serious presentations of common malignancies. Early diagnosis and treatment of these conditions can significantly affect the patient's clinical outcome.

Diffuse Alveolar Hemorrhage due to Acute Mitral Valve Regurgitation.

Diffuse alveolar hemorrhage (DAH) can be caused by several etiologies including vasculitis, drug exposure, anticoagulants, infections, mitral valve stenosis, and regurgitation. Chronic mitral valve regurgitation (MR) has been well documented as an etiological factor for DAH, but there have been only a few cases which have reported acute mitral valve regurgitation as an etiology of DAH. Acute mitral valve regurgitation can be a life-threatening condition and often requires urgent intervention. In rare cases, acute mitral regurgitation may result in a regurgitant jet which is directed towards the right upper pulmonary vein and may specifically cause right-sided pulmonary edema and right-sided DAH. Surgical repair of the mitral valve results in rapid resolution of DAH. Acute MR should be considered as a possible etiology in patients presenting with unilateral pulmonary edema, hemoptysis, and DAH.

Principles of physics in surgery: the laws of mechanics and vectors physics for surgeons-part 2.

In this sequel, to an earlier article, we discuss the laws of Mechanics, Thermodynamics and Vectors as they apply to soft and bony tissues. These include the Laplace's Law as applied to colonic perforation, compression therapy, parturition, variceal rupture, disc herniations etc. The Pascal's Law finds use in hernia repair and the Heimlich maneuver. Trigonometrically derived components of forces, acting after suturing, show ways to reduce cut-through; the thickness and the bite of suture determines the extent of tissue reaction. The heating effect of current explains the optimum gap between the prongs of a bipolar cautery and the use of law of transfer of heat in determining relation between healthy wound healing and ambient temperature.

Comparison of bleeding complications with omega-3 fatty acids + aspirin + clopidogrel--versus--aspirin + clopidogrel in patients with cardiovascular disease.

Fish oil is used to lower triglycerides and for the secondary prevention of cardiovascular events in patients with coronary artery disease. Many of these patients will also be taking aspirin and clopidogrel. Any of these medications alone can increase the risk of bleeding; however, the risk of bleeding in patients taking all 3 of these medications has not been studied. We retrospectively reviewed the medical records for bleeding complications in 182 patients, most with coronary artery disease (mean age 61 +/- 11 years, 82% men) and being treated with high-dose fish oil (mean dose 3 +/- 1.25 g), aspirin (mean dose 161 +/- 115 mg), and clopidogrel (mean dose 75 mg), and in 182 age- and gender-matched controls treated with aspirin and clopidogrel alone. During a mean follow-up period of 33 months, 1 major bleeding episode occurred in the treatment group and no major bleeding episodes occurred in the control group (p = 1.0). During follow-up, 4 minor bleeding episodes (2.2%) occurred in the treatment group and 7 (3.9%) in the control group. More patients had minor bleeding complications in the control group than in the treatment group; however, the difference was not statistically significant (p = 0.5). In conclusion, high-dose fish oil is safe in combination with aspirin and clopidogrel and does not increase the risk of bleeding compared with that seen with aspirin and clopidogrel alone.

Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study).

BACKGROUND: Atrial arrhythmias are common early after atrial fibrillation (AF) ablation. We hypothesized that empirical antiarrhythmic drug (AAD) therapy for 6 weeks after AF ablation would reduce the occurrence of atrial arrhythmias. METHODS AND RESULTS: We randomized consecutive patients with paroxysmal AF undergoing ablation to empirical antiarrhythmic therapy (AAD group) or no antiarrhythmic therapy (no-AAD group) for the first 6 weeks after ablation. In the no-AAD group, only atrioventricular nodal blocking agents were prescribed. All patients wore a transtelephonic monitor for 4 weeks after discharge and were reevaluated at 6 weeks. The primary end point of the study was a composite of (1) atrial arrhythmias lasting more than 24 hours; (2) atrial arrhythmias associated with severe symptoms requiring hospital admission, cardioversion, or initiation/change of antiarrhythmic drug therapy; and (3) intolerance to antiarrhythmic agent requiring drug cessation. Of 110 enrolled patients (age 55+/-9 years, 71% male), 53 were randomized to AAD and 57 to no-AAD. There was no difference in baseline characteristics between groups. During the 6 weeks after ablation, fewer patients reached the primary end point in the AAD compared with the no-AAD group (19% versus 42%; P=0.005). There remained fewer events in the AAD group (13% versus 28%; P=0.05) when only end points of AF >24 hours, arrhythmia-related hospitalization, or electrical cardioversion were compared. CONCLUSIONS: AAD treatment during the first 6 weeks after AF ablation is well tolerated and reduces the incidence of clinically significant atrial arrhythmias and need for cardioversion/hospitalization for arrhythmia management.

Treatment nonseeking in alcohol users: a community-based study from North India.

OBJECTIVE: This study examined the reasons given for not seeking treatment by problem alcohol users who live close to a community outreach de-addiction center. METHOD: Consecutive households in the community were contacted, and inquiry identified 495 male family members who were using alcohol, 163 of whom reported use of alcohol in the previous year. Of these 163 subjects, the 79 who scored above the cut-off of > or = 8 on the Alcohol Use Disorders Identification Test were further evaluated using a semistructured interview schedule to determine their reasons for not seeking treatment. RESULTS: The majority (n = 40) considered alcohol use a "social" problem. Among the reasons for not seeking treatment, the two most commonly cited were "ashamed to admit problems" and "treatment does not help" in 26.5% (n = 21) and 22.8% (n = 18), respectively. CONCLUSIONS: The reasons for not seeking treatment for alcohol problems in this sample of Indian men resemble those cited in the literature. The data highlight the need for action to improve outreach to problem alcohol users.