Survey of alcohol-related cirrhosis at a tertiary care center in North East India

Background

Alcohol use is increasing in North East India and is important to estimate the influence of these changes in the epidemiology of alcohol related cirrhosis.

Methods

Among 1000 consecutive patients of cirrhosis, diagnosed by a combination of clinical, radiological and/or histopathological features, etiology was established by history of significant alcohol abuse, determining viral and autoimmune markers and by metabolic screening. Patients not confirmed to be cirrhotic were excluded from the study. All cases were studied to determine clinical features, complications, disease prognosis, and mortality. Alcoholic cirrhotics were then compared with nonalcohol etiology.

Results

72.2 % alcoholic cirrhosis were compared with 27.8 % patients of nonalcohol etiology and alcoholic cirrhotics were younger (45?+?9.4 years vs. 47.9?+?12.5 years), predominantly males (M/F ratio 37:1 vs. 1.8:1) with significantly high incidence of jaundice (38.5 % vs. 30.5 %), night blindness (14.4 % vs. 3.6 %), ascites (76.3 % vs. 69.1 %), upper gastrointestinal bleed (46.4 % vs. 34.5 %), and hepatic encephalopathy (24.1 % vs. 10.4 %). Biochemical parameters that were significantly higher in alcoholics were mean bilirubin (4.7?+?8.7 vs. 3.1?+?4.7 mg/dL), AST/ALT ratio (2.03 vs. 1.4), gamma-glutaryl transaminase levels (209.7?+?37.9 vs. 93.9?+?14 IU/mL), and serum ammonia (75.1?+?55.7 vs. 52.1?+?45.4 mg/dL). Mean model for end-stage liver disease, scores, and Child C disease was significantly higher in alcoholics (18.6?+?7.7 vs. 15.6?+?6.4) and (54.1 % vs. 37 %), respectively, representing advanced disease at presentation. Mortality within 1 month was significantly higher among alcoholic cirrhosis (9.8 % vs. 3.2 %).

Conclusion

Thus, alcoholic cirrhosis is of major concern in North East India as majority patients are in most productive age group and presented with advanced disease. Short-term mortality was high among alcoholic cirrhotics. Proper education and legislation are essential to mitigate the consequences of this disease.

     

Implementation of a CKD Checklist for Primary Care Providers

Background and objectives

CKD is associated with significant morbidity, mortality, and financial burden. Practice guidelines outlining CKD management exist, but there is limited application of these guidelines. Interventions to improve CKD guideline adherence have been limited. This study evaluated a new CKD checklist (a tool outlining management guidelines for CKD) to determine whether implementation in an academic primary care clinic improved adherence to guidelines.

Design, setting, participants, & measurements

During a 1-year period (August 2012–August 2013), a prospective study was conducted among 13 primary care providers (PCPs), four of whom were assigned to use a CKD checklist incorporated into the electronic medical record during visits with patients with CKD stages 1–4. All providers received education regarding CKD guidelines. The intervention and control groups consisted of 105 and 263 patients, respectively. Adherence to CKD management guidelines was measured.

Results

A random-effects logistic regression analysis was performed to account for intra-group correlation by PCP assignment and adjusted for age and CKD stage. CKD care improved among patients whose PCPs were assigned to the checklist intervention compared with controls. Patients in the CKD checklist group were more likely than controls to have appropriate annual laboratory testing for albuminuria (odds ratio [OR], 7.9; 95% confidence interval [95% CI], 3.6 to 17.2), phosphate (OR, 3.5; 95% CI, 1.5 to 8.3), and parathyroid hormone (OR, 8.1; 95% CI, 4.8 to 13.7) (P<0.001 in all cases). Patients in the CKD checklist group had higher rates of achieving a hemoglobin A1c target<7% (OR, 2.7; 95% CI, 1.4 to 5.1), use of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker (OR, 2.1; 95% CI, 1.0 to 4.2), documentation of avoidance of nonsteroidal anti-inflammatory drugs (OR, 41.7; 95% CI, 17.8 to 100.0), and vaccination for annual influenza (OR, 2.1; 95% CI, 1.1 to 4.0) and pneumococcus (OR, 4.7; 95% CI, 2.6 to 8.6) (P<0.001 in all cases).

Conclusions

Implementation of a CKD checklist significantly improved adherence to CKD management guidelines and delivery of CKD care.     

Molecular mechanisms regulating CD13‐mediated adhesion

CD13/Aminopeptidase N is a transmembrane metalloproteinase that is expressed in many tissues where it regulates various cellular functions. In inflammation, CD13 is expressed on myeloid cells, is up‐regulated on endothelial cells at sites of inflammation and mediates monocyte/endothelial adhesion by homotypic interactions. In animal models the lack of CD13 alters the profiles of infiltrating inflammatory cells at sites of ischaemic injury. Here, we found that CD13 expression is enriched specifically on the pro‐inflammatory subset of monocytes, suggesting that CD13 may regulate trafficking and function of specific subsets of immune cells. To further dissect the mechanisms regulating CD13‐dependent trafficking we used the murine model of thioglycollate‐induced sterile peritonitis. Peritoneal monocytes, macrophages and dendritic cells were significantly decreased in inflammatory exudates from global CD13^KO animals when compared with wild‐type controls. Furthermore, adoptive transfer of wild‐type and CD13^KO primary myeloid cells, or wild‐type myeloid cells pre‐treated with CD13‐blocking antibodies into thioglycollate‐challenged wild‐type recipients demonstrated fewer CD13^KO or treated cells in the lavage, suggesting that CD13 expression confers a competitive advantage in trafficking. Similarly, both wild‐type and CD13^KO cells were reduced in infiltrates in CD13^KO recipients, confirming that both monocytic and endothelial CD13 contribute to trafficking. Finally, murine monocyte cell lines expressing mouse/human chimeric CD13 molecules demonstrated that the C‐terminal domain of the protein mediates CD13 adhesion. Therefore, this work verifies that the altered inflammatory trafficking in CD13^KO mice is the result of aberrant myeloid cell subset trafficking and further defines the molecular mechanisms underlying this regulation.     

Retinal manifestations in patients following COVID-19 infection: A consecutive case series

Purpose:To describe retinal manifestations seen in patients associated with COVID-19 infection at a multi-specialty tertiary care hospital in Southern India.Methods:In this retrospective chart review, all consecutive cases presenting to the Retina-Uveitis service from May 2020 to January 2021 with retinal manifestations associated with COVID-19 infection or its sequelae or as a result of treatment given for COVID-19 were included.Results:Of the 7 patients, 3 were female, and 4 were male. Four patients had onset of symptoms during the active phase of COVID-19 infection. Four had bilateral and three had unilateral involvement. The manifestations ranged from mild to vision threatening. Vision threatening manifestations included infections: endogenous endophthalmitis, candida retinitis and tubercular choroidal abscess and bilateral pre-foveal hemorrhages. Milder manifestations included paracentral acute middle maculopathy, central serous chorio-retinopathy and voriconazole induced visual symptoms. Final visual acuity was 6/36 or better in the four severe cases and 6/9 or better in the mild cases.Conclusion:This study highlights the retinal manifestations associated with COVID-19 infection and its sequelae. As these patients presented with an association with COVID-19 (either during or after recovery), ophthalmologists should be vigilant and screen for such entities in case of complaints of visual symptoms or in the presence of systemic sepsis. The outcomes can be good with prompt and aggressive management.     

Novel Endogenous Glycan Therapy for Retinal Diseases: Safety,In Vitro Stability,Ocular Pharmacokinetic Modeling,and Biodistribution

Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Müller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [³H]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous > retina > sclera/choroid > aqueous humor > cornea > lens. Area under the curve (0 to infinity) (AUC∞) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [³H]NA3 was excreted via urine and feces. NA3 was stable at 37°C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9563-1) contains supplementary material, which is available to authorized users.Key words: age-related macular degeneration (AMD), NA3 glycan, pharmacokinetics, safety     

Biomechanical characteristics of the horizontal mattress stitch: implication for double-row and suture-bridge rotator cuff repair

Background

We investigated the effects of bite-size horizontal mattress stitch (distance between the limbs passed through the tendon) on the biomechanical properties of the repaired tendon.

Methods

We anchored 20 bovine Achilles tendons to bone using no. 2 high-strength suture and 5-mm titanium suture anchors in a mattress–suture technique. Tendons were allocated randomly into two groups of ten each to receive stitches with a 4- or 10-mm bite. Specimens underwent cyclic loading from 5 to 30 N at 1 mm/s for 30 cycles, followed by tensile testing to failure. Gap formation, tendon strain, hysteresis, stiffness, yield load, ultimate load, energy to yield load, and energy to ultimate load were compared between groups using unpaired t tests.

Results

The 4-mm group had less (p < 0.05) gap formation and less (p < 0.05) longitudinal strain than did the 10-mm group. Ultimate load (293.6 vs. 148.9 N) and energy to ultimate load (2,563 vs. 1,472 N-mm) were greater (p < 0.001) for the 10-mm group than the 4-mm group. All tendons repaired with 4-mm suturing failed at the suture–tendon interface, with sutures pulling through the tendon, whereas the suture itself failed before the tendon did in seven of the ten specimens in the 10-mm group.

Conclusions

Whereas a 4-mm bite fixed the tendon more tightly but at the cost of decreased ultimate strength, a 10-mm bite conveyed greater ultimate strength but with increased gap and strain. These results suggest that for the conventional double-row repair, small mattress stitches provide a tighter repair, whereas large stitches are beneficial to prevent sutures from pulling through the tendon after surgery. For suture-bridge rotator cuff repair, large stitches are beneficial because the repaired tendon has a higher strength, and the slightly mobile medial knot can be tightened by lateral fixation.     

Challenges in optimizing sample preparation and LC‐MS/MS conditions for the analysis of carglumic acid,an N‐acetyl glutamate derivative in human plasma

This paper describes a systematic approach to overcoming challenges in developing a robust and selective liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for reliable and precise determination of carglumic acid in human plasma. Sample extraction was tested on several reversed‐phase solid‐phase extraction (SPE) sorbents with different chemistries, such as hydrophobic C18, hydrophilic‐lipophilic balance, and mixed‐mode cation and anion exchange. The best recovery under the optimized extraction conditions was obtained with Oasis MAX (30 mg, 1cc) mixed‐mode anion exchange (~ 50%) cartridge, compared to other sorbents from 100 μL plasma sample. Complete analytical separation of carglumic acid and carglumic acid‐13C5 15N as an internal standard (IS) from endogenous plasma components was achieved on ACE 5CN (150 × 4.6 mm, 5 µm) column under isocratic conditions using acetonitrile:methanol (50:50, v/v) ? 0.1% acetic acid in water [80:20, v/v] as the mobile phase. The deprotonated precursor → product ion transitions for carglumic acid (189/146) and IS (195/152) were monitored in the negative ionization mode on a triple quadrupole mass spectrometer. The regression curves were linear over a concentration range of 6.00‐6000 ng/mL (r² ≥ 0.9987). Matrix effect was evaluated in terms of IS‐normalized matrix factors, which ranged from 0.95 to 1.01 across four quality control levels. Intra‐ and inter‐batch accuracy and precision, and the stability of carglumic acid in spiked plasma samples were assessed under different conditions. The method was applied to assess the pharmacokinetics of 100 mg/kg body weight carglumic acid in a healthy Indian subject. Copyright © 2015 John Wiley & Sons, Ltd.     

Perioperative complications of robotic sacrocolpopexy for post-hysterectomy vaginal vault prolapse

Introduction and hypothesis

Open abdominal sacrocolpopexy has been the preferred treatment for post-hysterectomy vaginal vault prolapse. In light of the rise in popularity of less invasive robotic sacrocolpopexy, our objective was to compare perioperative complications of robotic vs open sacrocolpopexy.

Methods

This was a single-institution, retrospective cohort study of robotic and open sacrocolpopexies. Robotic sacrocolpopexies performed between 1 January 2007 and 31 December 2009 were compared with open cases performed between 1 January 2002 and 31 December 2006. Baseline and intraoperative variables of the groups were compared. Complications were compared univariately and in a multivariable logistic regression model to adjust for prior transabdominal surgery.

Results

A total of 50 robotic and 87 open sacrocolpopexies were analyzed. Baseline characteristics were similar, but patients in the open group had more prior transabdominal surgeries. The robotically assisted group had decreased estimated blood loss (median, 100 mL vs 150 mL; P?=?0.002) and hospital stay (median, 2 days vs 3 days; P?P?P?=?0.02), and vaginotomy (24.0 % [12 out of 50] vs 5.7 % [5 out of 87]; P?=?0.003). Two patients in the robotically assisted group had postoperative hernia. There were no differences in rates of ureteral or bowel injury, urinary tract infection, ileus, bowel obstruction, or overall complications.

Conclusions

Overall complication rates of robotic and open sacrocolpopexy were not significantly different. The robotically assisted group experienced shorter hospital stay but increased operative times and increased incidence of cystotomy and vaginotomy, possibly reflecting the learning curve of robotic sacrocolpopexy.