The Future of Renal Denervation in Resistant Hypertension

Resistant hypertension, defined as inadequate blood pressure control despite three or more antihypertensive medications at maximally tolerated doses, is strongly linked to increased cardiovascular morbidity and mortality. Increased renal afferent and efferent sympathetic activity carried by nerves which arborize the adventitia of the renal arteries, appears to be central to the pathobiology of resistant hypertension. Historical experience indicates that surgical denervation and/or sympathectomy often dramatically reduced blood pressure in patients with malignant hypertension. Catheter-based radio-frequency renal denervation was developed in the past decade as a percutaneous adaptation of surgical denervation. Percutaneous renal denervation using a variety of systems has demonstrated to date, in non-randomized and unblinded studies, dramatic reductions in office-based blood pressure, but more modest impact on ambulatory blood pressure. The only single, appropriately powered, blinded, sham-controlled study of renal denervation conducted to date, however, failed to meet its primary endpoint, casting doubt on the value of the therapy. Ancillary benefits of renal denervation have been described in such conditions as diabetes mellitus, heart failure, and sleep apnea but require further study. While renal denervation is already widely available outside of the USA for commercial use, its utility in resistant hypertension must be vetted by further rigorous investigation before its use can be routinely recommended.     

Safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir in post-liver transplant patients with previous direct-acting antiviral failure: Six case reports

BACKGROUNDDirect-acting antiviral (DAA) therapy regimens are highly effective at eliminating hepatitis C virus (HCV) infection but rates of sustained virologic response (SVR) are lower in patients with decompensated cirrhosis or hepatocellular carcinoma. Since many of these patients will be referred for liver transplant, they will require retreatment after transplantation. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is recommended by guidelines as the preferred regimen to treat HCV in DAA-experienced patients following liver transplant however there is limited data.CASE SUMMARYWe present the cases of six liver transplant recipients who had previous treatment failure with sofosbuvir-based DAA therapy prior to transplantation and who then received SOF/VEL/VOX after transplant.CONCLUSIONThis case series demonstrate the real-world efficacy and safety of SOF/VEL/VOX in the post liver transplant setting. Treatment was successful with all patients achieving SVR, it was well tolerated, and there were minimal drug-drug interactions with their immunosuppressants.     

Is liquid heparin comparable to dry balanced heparin for blood gas sampling in intensive care unit?

Introduction:

Blood gas (BG) analysis is required for management of critically ill patients in emergency and intensive care units. BG parameters can be affected by the type of heparin formulations used-liquid heparin (LH) or dry balanced heparin (DBH). This study was conducted to determine whether blood gas, electrolyte, and metabolite estimations performed by using DBH and LH are comparable.

Materials and Methods:

A prospective study was conducted at pediatric intensive care unit (PICU) of a tertiary care hospital. Paired venous samples were collected from 35 consecutive children in commercially prepared DBH syringes and custom-prepared LH syringes. Samples were immediately analyzed by blood gas analyzer and compared for pH, pCO₂, pO₂, HCO₃⁻, Na⁺, K⁺, Cl^-, and lactate. Paired comparisons were done and agreement was assessed by Bland-Altman difference plots. The 95% limits of absolute agreement (LOA) were compared with the specifications for total allowable error (TEa).

Results:

The P values were significant for all measured parameters, with the exception of pCO₂ and K +. Bland-Altman difference plots showed wide LOA for pCO₂, pO₂, HCO₃⁻, Na⁺, K⁺, and Cl⁻ when compared against TEa. For pCO₂, HCO₃⁻, Na⁺, K⁺, and Cl⁻, 40%, 23%, 77%, 34%, and 54% of samples were outside the TEa limits, respectively, with LH.

Conclusion:

Our study showed that there is poor agreement between LH and DBH for the BG parameters pCO2, pO₂, HCO3^-, K⁺, Na⁺, and Cl⁻ and, thus, are not comparable. But for pH and lactate, LH and DBH can be used interchangeably.     

The number of cardiac myocytes in the hypertrophic and hypotrophic left ventricle of the obese and calorie-restricted mouse heart

Changes in body mass due to varying amounts of calorie intake occur frequently with obesity and anorexia/cachexia being at opposite sides of the scale. Here, we tested whether a high-fat diet or calorie restriction (CR) decreases the number of cardiac myocytes and affects their volume. Ten 6–8-week-old mice were randomly assigned to a normal (control group, n = 5) or high-fat diet (obesity group, n = 5) for 28 weeks. Ten 8-week-old mice were randomly assigned to a normal (control group, n = 5) or CR diet (CR group, n = 5) for 7 days. The left ventricles of the hearts were prepared for light and electron microscopy, and analysed by design-based stereology. In CR, neither the number of cardiac myocytes, the relationship between one- and multinucleate myocytes nor their mean volume were significantly different between the groups. In contrast, in the obese mice we observed a significant increase in cell size combined with a lower number of cardiomyocytes (P < 0.05 in the one-sided U-test) and an increase in the mean number of nuclei per myocyte. The mean volume of myofibrils and mitochondria per cardiac myocyte reflected the hypertrophic and hypotrophic remodelling in obesity and CR, respectively, but were only significant in the obese mice, indicating a more profound effect of the obesity protocol than in the CR experiments. Taken together, our data indicate that long-lasting obesity is associated with a loss of cardiomyocytes of the left ventricle, but that short-term CR does not alter the number of cardiomyocytes.     

Retention of strong intramolecular hydrogen bonds in high polarity solvents in binaphthalene–benzamide derivatives: extensive NMR studies

Advanced multidimensional NMR techniques have been employed to investigate the intramolecular hydrogen bonds (HBs) in a series of N,N′-([1,1′-binaphthalene]-2,2′-diyl)bis(benzamide) derivatives, with the site-specific substitution of different functional groups. The existence of intramolecular HBs and the elimination of any molecular aggregation and possible intermolecular HBs are ascertained by various experimental NMR techniques, including solvent polarity dependent modifications of HB strengths. In the fluorine substituted derivative, direct evidence for the engagement of organic fluorine in HB is obtained by the detection of heteronuclear through-space correlation and the coupling between two NMR active nuclei where the transmission of spin polarization is mediated through HBs (^1hJ_FH). The extent of reduction in the strength of ^1hJ_FH on dilution with high polarity solvents directly provided the qualitative measure of HB strength. The HB, although becoming weakened, does not get nullified even in pure high polarity solvent, which is attributed to the structural constraints. The rate of exchange of a labile hydrogen atom with the deuterium of the solvent permitted the measurement of their half-lives, that are correlated to the relative strengths of HBs. The experimental NMR findings are further validated by XRD and DFT-based theoretical computations, such as, NCI and QTAIM.

NMR studies reveal very strong hydrogen bond unbreakable even in high polarity solvents.     

Pheochromocytoma Management,Outcomes and the Role of Cortical Preservation

Objectives

To evaluate the management and outcome of children with pheochromocytoma and determine the role of cortex preservation in cases of bilateral disease.

Methods

Retrospective review of children, below 12 y of age, with pheochromocytoma managed between November 2003 and December 2012 was done.

Results

Twelve patients, nine boys and three girls with median age 9 y were enroled. Eleven (92 %) had adrenal tumors and in one it was extra-adrenal. Five (42 %) had bilateral disease. Ten presented with hypertension, one with headache and one with abdominal pain and fever. All were stabilized pre-operatively with alpha and beta blockers and volume expansion. Six children with unilateral disease underwent total adrenalectomy. Out of five with bilateral disease, one child underwent bilateral total adrenalectomy and was later started on hormone replacement. Remaining four underwent total adrenalectomy on one side and partial on the other side. Post-operatively all became symptom free and normotensive and were off medications within 1 mo. Two children developed recurrence 1 mo post-operatively, one with an initial unilateral pheochromocytoma and one with paraganglionoma. At the last follow up, 10 out of 12(83 %) were disease free while two with recurrence are still awaiting surgery.

Conclusions

Surgical resection of pheochromocytoma is effective treatment to achieve cure and prolong survival. Cortex preservation should be done in bilateral disease as risk of recurrence in such cases seems to be of lesser significance as compared to the morbidity and mortality of adrenal insufficiency and consequent lifelong hormone replacement.     

A Survey of Pulmonary Function Abnormalities Following Thoracotomy

Objective

To study the incidence and type of pulmonary function abnormalities after thoracotomy in children.

Methods

Children below 12 y of age who had undergone thoracotomy for any condition and have at least 2 y follow up were included in the study. Detailed assessment of the patients included history and general examination, clinical assessment of pulmonary function, bedside tests to assess pulmonary function and laboratory pulmonary function test using portable spirometer.

Results

Fifty two patients were included in the study. Twenty-seven were cases of esophageal atresia with trachea-esophageal fistula (EATEF), nine pulmonary metastasis from abdominal solid tumors, six mediastinal masses, three hydatid cyst, three eventration of diaphragm, two bronchiectasis, and one each of H-type TEF and congenital esophageal stenosis. The mean age at the time of evaluation was 6.3 y (range 2–18 y). While all the patients were clinically assessed, only 25 (48 %) were eligible for bedside tests and 23 (44 %) for spirometery. The incidences of abnormalities picked were: dyspnea during exercise 8/52 (15.4 %), dyspnea on exercise and on climbing stairs 1/52 (2 %), decreased breath holding time 2/25 (8 %), abnormal incentive spirometry 1/25 (4 %), mild restrictive pattern on pulmonary function test (PFT) 11/23 (47.8 %), moderate restrictive pattern on PFT 2/23 (8.7 %). None had an obstructive pattern on PFT.

Conclusions

Though the incidences of pulmonary function abnormalities were high, these were of mild grade. Close follow up of patients after thoracotomy would be needed for early pick up and appropriate management of these abnormalities to prevent long-term consequences.     

Recent progress in development of 2,3-diaminomaleonitrile (DAMN) based chemosensors for sensing of ionic and reactive oxygen species

2,3-Diaminomaleonitrile (DAMN) has proved to be a valuable organic π-conjugated molecule having many applications in the area of chemosensors for sensing of ionic and neutral species because of its ability to act as a building block for well-defined molecular architectures and scaffolds for preorganised arrays of functionality. In this article, we discussed the utilization of 2,3-diaminomaleonitrile (DAMN) for the design and development of chemosensor molecules and their application in the area of metal ion, anion and reactive oxygen species sensing. Along with these, we present different examples of DAMN based chemosensors for multiple ion sensing. We also discuss the ion sensing mechanism and potential uses in other related areas of research.

2,3-Diamniomaleonitrile (DAMN) is valuable π-conjugated organic scaffold molecule for designing of efficient chemosensors for sensing of ionic and Reactive Oxygen Species (ROS).     

Transjugular intrahepatic portosystemic shunt in cirrhosis: An exhaustive critical update

More than five decades after it was originally conceptualized as rescue therapy for patients with intractable variceal bleeding, the transjugular intrahepatic portosystemic shunt(TIPS) procedure continues to remain a focus of intense clinical and biomedical research. By the impressive reduction in portal pressure achieved by this intervention, coupled with its minimally invasive nature, TIPS has gained increasing acceptance in the treatment of complications of portal hypertension. The early years of TIPS were plagued by poor long-term patency of the stents and increased incidence of hepatic encephalopathy. Moreover, the diversion of portal flow after placement of TIPS often resulted in derangement of hepatic functions, which was occasionally severe. While the incidence of shunt dysfunction has markedly reduced with the advent of covered stents, hepatic encephalopathy and instances of early liver failure continue to remain a significant issue after TIPS. It has emerged over the years that careful selection of patients and diligent post-procedural care is of paramount importance to optimize the outcome after TIPS. The past twenty years have seen multiple studies redefining the role of TIPS in the management of variceal bleeding and refractory ascites while exploring its application in other complications of cirrhosis like hepatic hydrothorax, portal hypertensive gastropathy, ectopic varices, hepatorenal and hepatopulmonary syndromes, non-tumoral portal vein thrombosis and chylous ascites. It has also been utilized to good effect before extrahepatic abdominal surgery to reduce perioperative morbidity and mortality. The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.