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Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Rice is a principal food crop for more than half of the global population. Grain number and grain weight (2Gs) are the two complex traits controlled by several quantitative trait loci (QTLs) and are considered the most critical components for yield enhancement in rice. Novel molecular biology and QTL mapping strategies can be utilized in dissecting the complex genetic architecture of these traits. Discovering the valuable genes/QTLs associated with 2Gs traits hidden in the rice genome and utilizing them in breeding programs may bring a revolution in rice production. Furthermore, the positional cloning and functional characterization of identified genes and QTLs may aid in understanding the molecular mechanisms underlying the 2Gs traits. In addition, knowledge of modern genomic tools aids the understanding of the nature of plant and panicle architecture, which enhances their photosynthetic activity. Rice researchers continue to combine important yield component traits (including 2Gs for the yield ceiling) by utilizing modern breeding tools, such as marker-assisted selection (MAS), haplotype-based breeding, and allele mining. Physical co-localization of GW7 (for grain weight) and DEP2 (for grain number) genes present on chromosome 7 revealed the possibility of simultaneous introgression of these two genes, if desirable allelic variants were found in the single donor parent. This review article will reveal the genetic nature of 2Gs traits and use this knowledge to break the yield ceiling by using different breeding and biotechnological tools, which will sustain the world's food requirements.

Background: Lupus nephritis (LN) is associated with poor outcomes and a significant risk of progression to end-stage renal disease (ESRD). Some patients with resistant LN do not respond adequately to current treatment options and need alternative strategies or therapies., Objective: The objective is to evaluate the efficacy and safety of rituximab as a re-induction therapy (Re-RTX) followed by maintenance therapy for patients with resistant LN., Methods: Twenty-four patients with resistant LN (failed initial induction therapy or severe relapse after remission) were analyzed. Re-RTX was co-administered with other immunosuppressants. The primary KDIGO criteria outcomes included renal response (complete and partial), disease progression, relapses, and infections., Results: The median age was 28 years (IQR 24.5-42), and the female-to-male ratio was 11:1. All patients had active LN, and 91.3% had proliferative LN. Baseline creatinine was 1.075 mg% (IQR 0.7-1.38), and mean urine protein-to-creatinine ratio (UPCR) was 4.9 (IQR 2.8-6.65). Of the patients receiving RTX as re-induction therapy, 66.6% (16/24) had failed initial induction therapy with other immunosuppressants, whereas 33.3% (8/24) had severe relapse during maintenance therapy.Re-RTX had a favorable renal response at 6 months, with 91.7% of the patients responding (20.8% complete response and 70.8% partial response). At 12 months, 58.3% of the patients maintained a renal response (25% complete response and 33.3% partial response). Approximately one-third of patients relapsed within a year.Fourteen patients (58.3%) continued RTX maintenance therapy with two different treatment regimens. At 6 months, Regimen-1 (500 mg every 6 months) resulted in a partial response in 43% (3/7) and relapse in 57% (4/7) of patients. Regimen 2 (1 g dose per year) achieved a complete response in 28.5% (2/7) and a partial response in 71.5% (5/7) with no relapses at 6 months.At a median follow-up of 29 months, adverse renal outcomes were observed in 29.16% of the patients with progression to advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). The overall use of Re-RTX was considered safe, with a reported infection prevalence of 16%, which is comparable to the existing data., Conclusion: Re-RTX demonstrated efficacy and safety as an induction therapy for resistant LN. However, the response waned after 1 year, underscoring the need for optimized maintenance therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Sustained low-efficiency dialysis is a hybrid form of kidney replacement therapy that has gained increasing popularity as an alternative to continuous forms of kidney replacement therapy in intensive care unit settings. During the COVID-19 pandemic, the shortage of continuous kidney replacement therapy equipment led to increasing usage of sustained low-efficiency dialysis as an alternative treatment for acute kidney injury. Sustained low-efficiency dialysis is an efficient method for treating hemodynamically unstable patients and is quite widely available, making it especially useful in resource-limited settings. In this review, we aim to discuss the various attributes of sustained low-efficiency dialysis and how it is comparable to continuous kidney replacement therapy in efficacy, in terms of solute kinetics and urea clearance, and the various formulae used to compare intermittent and continuous forms of kidney replacement therapy, along with hemodynamic stability. During the COVID-19 pandemic, there was increased clotting of continuous kidney replacement therapy circuits, which led to increased use of sustained low-efficiency dialysis alone or together with extra corporeal membrane oxygenation circuits. Although sustained low-efficiency dialysis can be delivered with continuous kidney replacement therapy machines, most centers use standard hemodialysis machines or batch dialysis systems. Even though antibiotic dosing differs between continuous kidney replacement therapy and sustained low-efficiency dialysis, reports of patient survival and renal recovery are similar for continuous kidney replacement therapy and sustained low-efficiency dialysis. Health care studies indicate that sustained low-efficiency dialysis has emerged as a cost-effective alternative to continuous kidney replacement therapy. Although there is considerable data to support sustained low-efficiency dialysis treatments for critically ill adult patients with acute kidney injury, there are fewer pediatric data, even so, currently available studies support the use of sustained low-efficiency dialysis for pediatric patients, particularly in resource-limited settings., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Obesity has continued to emerge as a worldwide pandemic and has been associated with a significant increase in associated comorbidities. These include well-known conditions such as hypertension and diabetes, as well as lesser-known conditions such as obesity-related glomerulopathy (ORG). The main etiology of ORG is podocyte damage, but contributing theories include dysfunctional renin-angiotensin-aldosterone system activation, hyperinsulinemia and lipid deposition. Recent advances have made strides in understanding the complex pathophysiology of ORG. The key to treating ORG is weight loss and proteinuria reduction. Lifestyle modification, pharmacological interventions and surgery are mainstays of management. A special focus on obese children is required, as childhood obesity tracks into adulthood and primary prevention is key. In this review we discuss the pathogenesis, clinical features and established and newer treatment modalities of ORG., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Autosomal dominant polycystic kidney disease, also known as ADPKD, is the most common hereditary kidney disease, affecting different age groups. ADPKD can eventually lead to end-stage renal disease. The etiology of ADPKD is genetic, resulting in the formation of cysts containing fluids on the kidneys. Patients with ADPKD present a range of symptoms following a decline in kidney function. Pain, stones, proteinuria and osteoporosis are few of the many symptoms, resulting from decreased kidney function. Tolvaptan, a selective V2 receptor antagonist, is the etiological treatment used for ADPKD. In this paper, we conducted a systematic review of the literature between 2011 and 2021 to gather data regarding the tolerability and efficacy of tolvaptan use in ADPKD. A total of 22 trials were reviewed. Tolvaptan efficacy in the trials was measured using changes in eGFR or changes in total kidney volume. Results showed that tolvaptan use in ADPKD was associated with a slower decline in kidney function and a decrease in total kidney volume. Side effects of this drug include polyuria, nocturia and polydipsia along with hepatotoxicity. The two biggest trials, TEMPO and REPRISE, change in eGFR from pre-treatment baseline to post-treatment was 1.3 mL/min/1.73 for REPRISE and 1 mL/min/1.73 for TEMPO 3:4. A mean decrease of 49% in total kidney volume from baseline to post-treatment was found in the TEMPO 3:4 study., Competing Interests: Rupesh Raina and Ahmad Houry are co-first authors. The authors declare no conflicts of interest., (© 2022 Raina et al.)

Atypical hemolytic uremic syndrome (aHUS) an important form of a thrombotic microangiopathy (TMA) that can frequently lead to acute kidney injury (AKI). An important subset of aHUS is the anti-factor H associated aHUS. This variant of aHUS can occur due to deletion of the complement factor H genes, CFHR1 and CFHR3 , along with the presence of anti-factor H antibodies. However, it is a point of interest to note that not all patients with anti-factor H associated aHUS have a CFHR1/R3 deletion. Factor-H has a vital role in the regulation of the complement system, specifically the alternate pathway. Therefore, dysregulation of the complement system can lead to inflammatory or autoimmune diseases. Patients with this disease respond well to treatment with plasma exchange therapy along with Eculizumab and immunosuppressant therapy. Anti-factor H antibody associated aHUS has a certain genetic predilection therefore there is focus on further advancements in the diagnosis and management of this disease. In this article we discuss the baseline characteristics of patients with anti-factor H associated aHUS, their triggers, various treatment modalities and future perspectives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor C-YY declared a shared parent affiliation with the author RS at the time of review., (Copyright © 2022 Raina, Mangat, Hong, Shah, Nair, Abboud, Bagga and Sethi.)

Rice false smut (RFS), an emerging major fungal disease worldwide caused by Ustilaginoidea virens, affects rice grain quality and yield. RFS cause 2.8-49% global yield loss depending upon disease severity and cultivars. In India, the yield loss due to RFS ranged from 2 to 75%. Identification of the genes or quantitative trait loci (QTLs) governing disease resistance would be of utmost importance towards mitigating the economic losses incurred due to RFS. Here, we report mapping of RFS resistance QTLs from a resistant breeding line RYT2668. The mapping population was evaluated for RFS resistance under the field condition in three cropping seasons 2013, 2015, and 2016. A positive correlation among infected panicle/plant, total smut ball/panicle, and disease score was observed in the years 2013, 2015, and the mean data. A total of seven QTLs were mapped on rice chromosomes 2, 4, 5, 7, and 9 using 2326 single nucleotide polymorphism markers. Of these, two QTLs, qRFSr5.3 and qRFSr7.1a, were associated with the infected panicle per plant, one QTL qRFsr9.1 with total smut ball per panicle, and four QTLs qRFSr2.2, qRFSr4.3, qRFSr5.4, and qRFSr7.1b with disease score. Among them, a novel QTL qRFSr9.1 on chromosome 9 exhibits the largest phenotypic effect. The prediction of putative candidate genes within the qRFSr9.1 revealed four nucleotide-binding sites-leucine-rich repeat (NBS-LRR) domain-containing disease resistance proteins. In summary, our findings mark the hotspot region of rice chromosomes carrying genes/QTLs for resistance to the RFS disease., (© 2021. Institute of Plant Genetics, Polish Academy of Sciences, Poznan.)

Aims: We assessed the geometry of transcatheter heart valve (THV) and valve function associated with SAPIEN 3 implantation in patients with bicuspid aortic valve (BAV) stenosis., Methods and Results: We included 280 consecutive patients who had a contrast computed tomography (CT) before and after transcatheter aortic valve implantation (TAVI) in our institution. Each THV was assessed by CT at five cross-sectional levels: inflow, annulus, mid, sinus, and outflow. The geometry of THV was assessed for eccentricity (1 - minimum diameter/maximum diameter) and expansion (CT derived external valve area/nominal external valve area). CT measurements and transthoracic echocardiogram data were compared between BAV and tricuspid aortic valve (TAV). Among 280 patients, 41 patients were diagnosed as BAV. Compared to TAV, BAV was associated with lower expansion at mid-level, sinus-level, and outflow-level (mid 94.1 ± 6.8% vs. 98.1 ± 7.8%; P = 0.002, sinus 95.9 ± 7.2% vs. 101.6 ± 8.5%; P < 0.001, outflow 107.6 ± 6.2% vs. 109.9 ± 6.6%; P = 0.043), and higher eccentricity at all levels [inflow 3.5% (1.9-5.3) vs. 6.0% (3.2-7.5); P < 0.001, annulus 3.1% (1.6-5.2) vs. 5.4% (3.1-7.8); P = 0.002, mid 3.0% (1.4-4.9) vs. 6.0% (3.3-10.4); P < 0.001, sinus 3.0% (1.7-5.1) vs. 7.6% (4.0-11.4); P < 0.001, and outflow 2.5% (1.3-4.3) vs. 4.9% (2.2-7.5); P < 0.001]. There were no differences in frequency of paravalvular leak ≥ moderate and mean post-procedural gradient between BAV and TAV., Conclusion: BAV patients have greater THV eccentricity at all levels and lower THV expansion at mid, sinus, and outflow levels than the TAV patients. There were no differences in parameters of valve function between BAV and TAV patients. Despite the observed geometrical differences, TAVI with SAPIEN 3 in BAV patients allows for feasible valve function.

Aims: Only a few studies have examined the respective impact of low flow (LF), low gradient (LG) and low ejection fraction (LEF) on outcomes following transcatheter aortic valve replacement (TAVR). The purpose of this study was to assess the impact of preprocedural stroke volume index, aortic valve gradient, left ventricular ejection fraction (LVEF) and different flow/gradient/LVEF patterns on the clinical outcomes of patients with severe aortic stenosis (AS) who undergo TAVR., Methods and Results: We analysed the clinical, echocardiographic, and outcome data collected in 770 patients with AS who underwent TAVR. Overall, 357 patients had normal flow (NF) AS and 413 had LF AS. Patients with NF had similar one-year mortality (12.0% vs. 15.0%, p=0.23) compared with those in the LF group. Overall, patients with NF and/or HG had lower one-year mortality rates (11.7 to 13%) compared to those with paradoxical LF-LG with NEF (19%) and those with classical LF-LG with LEF (27.3%). Low mean gradient was an independent predictor of all-cause mortality (hazard ratio: 1.14, per 10 mmHg decrease, p=0.02). Despite significant association in univariable analyses, LF and LEF were not found to be predictors of outcomes in multivariable analyses., Conclusions: Patients with HG and those with NF-LG have low one-year mortality rates following TAVR, whereas those with classical LF-LG and LEF and those with paradoxical LF-LG and NEF have high and intermediate risk of mortality, respectively. In contradiction to previous reports, LG but not LF or LEF is an independent predictor of late mortality in high-risk patients with severe AS undergoing TAVR.

Left ventricular outflow tract (LVOT) calcium is known to be associated with adverse procedural outcomes after transcatheter aortic valve implantation (TAVI), yet its effect on midterm outcomes has not been previously investigated. The aim of this study was to determine the influence of LVOT calcium on 2-year mortality after TAVI. A total of 537 consecutive patients underwent TAVI and 2 groups were established, stratified based on the severity of the LVOT calcium. The primary outcome was 2-year overall survival rate. The ≥moderate LVOT calcium group included 107 patients (19.9%) and the remaining 430 patients (80.1%) were included in the ≤mild LVOT calcium group. After a median follow-up of 717 days (interquartile range 484 to 828), the Kaplan-Meier analysis revealed that the 2-year overall survival probability was significantly lower in the ≥moderate LVOT calcium group than in the ≤mild LVOT calcium group (log-rank p = 0.001). On a Cox hazard model, ≥moderate LVOT calcium was associated with increased all-cause mortality after TAVI (hazard ratio 1.74, p = 0.009). In the subgroup analysis, based on valve designs, SAPIEN 3-TAVI done in the setting of ≥moderate LVOT calcium had a relatively similar survival probability as those of ≤mild LVOT calcium (log-rank p = 0.18), which is in contrast with older generation valves (log-rank p = 0.001). In conclusion, patients with ≥moderate LVOT calcium were shown to have a lower survival probability in the midterm follow-up after TAVI, compared with those with ≤mild LVOT calcium. Patients with high-grade LVOT calcium should be monitored with longer-term follow-ups after TAVI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: Self-expanding (SE) valves are characterized with long stent frame design and the radial force of the device exists both in the inflow and outflow level. Therefore, we hypothesized that device success of SE-valves may be influenced by ascending aortic dimensions (AAD). The aim of this study was to determine the influence of AAD on acute device success rates following SE transcatheter aortic valve replacement (TAVR)., Methods & Results: In 4 centers in the United States and Asia, 214 consecutive patients underwent SE-TAVR. Outcomes were assessed in line with Valve Academic Research Consortium criteria. AAD was defined as the sum of the short and long axis aortic diameter divided by 2. Overall, device success rate was 85.0%. Multivariate analysis revealed that increased AAD (Odds ratio 1.27) and % oversizing (Odds ratio 0.88) were found to be independent predictors of unsuccessful device implantation. The c-statistic of the model for device success was area under the curve 0.79, sensitivity 81.3% and specificity 44.0%. Co-existence of several risk factors was associated with an exponential fall to 64.2% in device success rate. For a large AAD, however, optimally oversized SE-valves (threshold 16.2%) resulted with high device success rates compared to suboptimal oversizing (88.6% vs. 64.2%, p=0.005)., Conclusions: Larger AAD and smaller degrees of oversizing were confirmed to be the most relevant predictors of unsuccessful device implantation following SE-valve implantations. Optimal oversizing of great significance was noted, particularly that with a large AAD., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study sought to develop a robust and definitive risk model for new permanent pacemaker implantation (PPMI) after SAPIEN 3 (third generation balloon expandable valve) (Edwards Lifesciences, Irvine, California) transcatheter aortic valve replacement (third generation balloon expandable valve TAVR), including calcification in the aortic-valvular complex (AVC)., Background: The association between calcium in the AVC and need for PPMI is poorly delineated after third generation balloon expandable valve TAVR., Methods: At Cedars-Sinai Heart Institute in Los Angeles, California, a total of 240 patients with severe aortic stenosis underwent third generation balloon expandable valve TAVR and had contrast computed tomography. AVC was characterized precisely by leaflet sector and region., Results: The total new PPMI rate was 14.6%. On multivariate analysis for predictors of PPMI, pre-procedure third generation balloon expandable valve TAVR, right bundle branch block (RBBB), shorter membranous septum (MS) length, and noncoronary cusp device-landing zone calcium volume (NCC-DLZ CA) were included. Predictive probabilities were generated using this logistic regression model. If 3 pre-procedural risk factors were present, the c-statistic of the model for PPMI was area under the curve of 0.88, sensitivity of 77.1%, and specificity of 87.1%; this risk model had high negative predictive value (95.7%). The addition of the procedural factor of device depth to the model, with the parameter of difference between implantation depth and MS length, combined with RBBB and NCC-DLZ CA increased the c-statistic to 0.92, sensitivity to 94.3%, specificity to 83.8%, and negative predictive value to 98.8% CONCLUSIONS: By using a precise characterization of distribution of calcification in the AVC in a single-center, retrospective study, NCC-DLZ CA was found to be an independent predictor of new PPMI post-third generation balloon expandable valve TAVR. The findings also reinforce the importance of short MS length, pre-existing RBBB, and ventricular implantation depth as important synergistic PPMI risk factors. This risk model will need validation by future prospective multicenter studies., (Copyright © 2017. Published by Elsevier Inc.)

Background: The aim of this study was to determine the influence of an elliptic annulus on acute device success rates following self-expanding (SE) transcatheter aortic valve replacement (TAVR) vs. balloon-expandable (BE) TAVR.Methods and Results:Outcomes were assessed using Valve Academic Research Consortium-2 definitions. Aortic annulus ratio (AAR) was measured as short axis diameter/long axis diameter. Mean AAR was 0.81±0.06. Patients were therefore divided into 2 groups: AAR <0.82 and AAR ≥0.82. For circular annuli (AAR ≥0.82; 363 patients), high device success rates were achieved in both valve groups (SE valve, 90.5% vs. BE valve, 95.0%, P=0.14). Conversely, for AAR <0.82 (374 patients), SE valves had lower device success rates than BE valves (82.5% vs. 95.3%, P=0.002). For elliptic annuli, SE-TAVR was an independent predictor of unsuccessful device implantation (OR, 6.34, P<0.001). Nonetheless, increased oversizing of SE valves for elliptic annuli was associated with an exponential rise in device success (threshold ≥17.5%; area under the curve, 0.83) but not for BE-TAVR. Furthermore, optimally oversized SE valves and BE valves had a similarly high device success for elliptic annuli (SE valve, 96.2% vs. BE valve, 95.3%)., Conclusions: For circular annuli, similarly high device success was achieved for the 2 valve types. Conversely, for elliptic annuli, SE valves had a lower device success than BE valves. Device success following optimal oversizing of SE valves, however, was similar to that for BE valves.

Aims: High aortic valve calcification (AVC) assessed with CT may be used to differentiate between severe and non-severe aortic stenosis (AS). Nonetheless, in some cases patients with low calcification are diagnosed with haemodynamically severe AS. The prevalence, mechanism of valve stenosis and implications for transcatheter aortic valve implantation (TAVI) of low AVC severe AS remain unclear. We assessed the clinical and haemodynamic characteristics and the outcome of patients with severe AS and low AVC that undergo TAVI., Methods and Results: Ninety-three patients that had low CT aortic valve calcification score (AVCS) were compared to 470 patients with high AVCS. High gradient severe AS was found among 53.8% (50/93) of the patients with low AVCS vs. 86% (404/470) of the patients with high AVCS (P < 0.001). Device success rate was similar between both groups. There were significantly lower rates of postprocedural paravalvular regurgitation (PVR) in the low AVCS group (≥ mild PVR: 12.9% vs. 23.6%; P = 0.03). Overall, there were only two cases (0.4%) of valve embolization in patients with high AVCS and 1 (1.1%) in patients with low AVCS (P = 0.42). Thirty-day mortality and major complications were similar between groups., Conclusion: Balloon-expandable TAVI in patients with a mildly calcified aortic valve was not associated with increased risk of valve embolization or mortality. We demonstrated high device success and lower rates of PVR for these patients. These findings suggest that in patients with evidence of haemodynamically severe AS at echocardiography, the presence of low ACVS at CT should not preclude the consideration of TAVI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aims: Calcified aortic stenosis (AS) and mitral annular calcification (MAC) have certain similar etiology and pathophysiological mechanisms. MAC is frequently encountered in pre-procedural computed tomography (CT) imaging of patients that undergo transcatheter aortic valve replacement (TAVR), but its prognostic implications for these patients have not been thoroughly investigated. This study sought to evaluate the prevalence of MAC among patients with severe AS and to assess the clinical implications of MAC on these patients during and following TAVR., Methods and Results: Consecutive patients that underwent TAVR were compared according to the existence of MAC and its severity in pre-TAVR CT scans. From the entire cohort of 761 patients, 49.3% had MAC, and 50.7% did not have MAC. Mild MAC was present in 231 patients (30.4%), moderate MAC in 72 patients (9.5%), and severe MAC in 72 patients (9.5%). Thirty-day mortality and major complications were similar between patients with and without MAC. In a multivariable survival analysis, severe MAC was found to be an independent strong predictor of overall mortality following TAVR (all-cause mortality: hazards ratio [HR] 1.95, 95% confidence interval [CI] 1.24-3.07, P = 0.004; cardiovascular mortality: HR 2.35, 95% CI 1.19-4.66; P = 0.01). Severe MAC was also found to be an independent strong predictor of new permanent pacemaker implantation (PPI) after TAVR (OR 2.83, 95% CI 1.08-7.47; P = 0.03)., Conclusion: Half of the patients with severe AS evaluated for TAVR were found to have MAC. Severe MAC is associated with increased all-cause and cardiovascular mortality and with conduction abnormalities following TAVR and should be included in future risk stratification models for TAVR., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)

Aims: The impact of left ventricular outflow tract calcification (LVOT-CA) on SAPIEN 3 transcatheter aortic valve replacement (S3-TAVR) is not well understood. The aims of the present study were to determine optimal device sizing for S3-TAVR in patients with or without LVOT-CA and to evaluate the influence of residual paravalvular leak (PVL) on survival after S3-TAVR in these patients., Methods and Results: This study analysed 280 patients (LVOT-CA=144, no LVOT-CA=136) undergoing S3-TAVR. Optimal annular area sizing was defined as % annular area sizing related to lower rates of ≥mild PVL. Annular area sizing was determined as follows: (prosthesis area/CT annulus area-1)×100. Overall, ≥mild PVL was present in 25.7%. Receiver operating characteristic curve analysis for prediction of ≥mild PVL in patients with LVOT-CA showed that 7.2% annular area sizing was identified as the optimal threshold (area under the curve [AUC] 0.71). Conversely, annular area sizing for no LVOT-CA appeared unrelated to PVL (AUC 0.58). Aortic annular injury was seen in four patients (average 15.5% annular area oversizing), three of whom had LVOT-CA. Although there was no difference in one-year survival between patients with ≥mild PVL and without PVL (log-rank p=0.91), subgroup analysis demonstrated that patients with ≥moderate LVOT-CA who had ≥mild PVL had lower survival compared to patients with ≥mild PVL and none or mild LVOT-CA (log-rank p=0.010)., Conclusions: In the setting of LVOT-CA, an optimally sized S3 valve is required to reduce PVL and to increase survival following TAVR.

Background: Significant paravalvular leak (PVL) occurs in up to 13% of patients after transcatheter aortic valve replacement (TAVR) with a balloon-expandable bioprosthesis. Transcatheter PVL repair has emerged as a less invasive alternative for this problem., Objectives: The aim of this study was to evaluate the safety, feasibility, and clinical outcomes of transcatheter PVL repair after TAVR with balloon-expandable valve., Methods: We retrospectively identified 15 patients who underwent 16 PVL repair procedures after the TAVR at our center. Procedural characteristics, results, and clinical outcomes were analyzed. The association of PVL repairs with subsequent hospitalizations and mortality was assessed and compared to 57 patients who did not undergo repair for at least moderate PVL after TAVR., Results: The PVL repair was successful in 13 (87%) patients, without significant procedure or device related complications. In patients with successful PVL repair, there was an improvement in symptom status, subsequent hospitalizations, and B-type natriuretic peptide levels. There was 1 (out of 13, 8%) death in the group of patients who successfully underwent PVL repair whereas 24 (out of 57, 42%) patients died during follow up in the group that did not undergo repair of their PVL. Similarly, there was significant reduction in the subsequent heart failure related hospitalization after the PVL repair, compared with the patients who did not undergo PVL repair (P = 0.03)., Conclusion: Transcatheter repair of PVL after TAVR can be safely and effectively accomplished in carefully selected patients, and may lead to reduction in hospitalizations, improvement in symptoms, and long-term survival. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Severe device landing zone calcification (DLZ-CA) predicted paravalvular leak (PVL) and post-dilatation (PD) after transcatheter aortic valve implantation (TAVI). The aim of this study was to determine the influence of DLZ-CA on PVL or PD rates after SAPIEN XT (XT) versus CoreValve (CV).We analyzed patients undergoing TAVI who had severe DLZ-CA. Severe DLZ-CA defined the upper left ventricular outflow tract calcification; the cross-sectional region 2 mm inferior to the annular plane. PVL was evaluated at 30days using transthoracic echocardiography. Overall, 133 patients had XT-TAVI and the remaining 41 patients had CV-TAVI. Two patients had annulus injury in the XT group (oversizing 20.2% and 20.5% for two XT cases). PD was less frequently performed in the XT group (34.1% versus 12.8%; P = 0.002), but PVL rates were similar between both groups (42.1% versus 41.5% for the XT and CV groups, respectively; P = 0.94). Importantly, excessive oversizing or the degree of filling volume was not associated with decreased PVL after XT-TAVI (P = non-significant for all). On multivariate analysis, CV-TAVI was found to be one of the independent predictors of need for PD (Odds ratio 3.63, 95% confidence interval 1.55 to 8.53, P = 0.003).In the setting of severe DLZ-CA, XT and CV have similar rates of PVL but XT had less need for PD. Excessive oversizing with XT carries a risk of root injury which could be further increased by DLZ-CA.

Objectives: Aortic valve preparation with balloon aortic valvuloplasty (BAV) has been previously considered mandatory during transcatheter aortic valve implantation (TAVI) procedures. BAV-inherent risks including stroke, conduction abnormalities, and reduced device profile size established the rationale for safe valve deployment without the need for aggressive valve preparation. We investigate the feasibility and safety of performing Sapien 3 (S3; Edwards Lifesciences) balloon-expandable TAVI with moderate or without predilation (PD)., Methods: We examined consecutive patients with severe aortic stenosis who underwent S3-TAVI at our institution. Overall, 119 patients underwent TAVI without PD and 126 with moderate PD (mean valvuloplasty balloon diameter, 15.3 ± 2.1 mm). TAVI endpoints and adverse events were considered according to the Valve Academic Research Consortium (VARC)-2 definitions., Results: Device success for the entire cohort was 98.8%. PD rates were similar between groups. Total fluoroscopy time and amount of contrast used were lower in the no PD group (13 min vs 16.2 min [P<.001] and 71.3 mL vs 81 mL [P=.03], respectively). All-cause mortality up to 30 days was 0% (0/119) in the no PD group vs 1.6% (2/126) in the moderate PD group (P=.49). VARC-2 defined complication rates at 30 days including cerebrovascular accident were similar between groups. Overall, there was no significant difference in survival rate between both groups (hazard ratio, 3.6; 95% confidence interval, 0.80-16.2; P=.09)., Conclusions: Balloon-expandable TAVI using the S3 device with moderate or without balloon PD is feasible and safe. Omission of PD in appropriate cases was associated with reduced fluoroscopy time and total contrast used without affecting procedural success.

Objectives: The aim of this study was to evaluate the impact of increased aortic angulation (AA) on acute procedural success following transcatheter aortic valve replacement (TAVR)., Background: The degree of angulation between the aorta and the heart can make accurate positioning of the bioprosthesis during TAVR more demanding, particularly in instances of an extremely angulated or horizontal aortic root. Nonetheless, there are limited data on the impact of AA on the acute success of TAVR., Methods: We assessed 582 patients who underwent TAVR at our institute and had contrast computed tomography available for AA evaluation. TAVR endpoints, device success, and adverse events were considered according to the Valve Academic Research Consortium-2 definitions., Results: The mean angulation of the aorta was 47.3 ± 8.7°. Patients were therefore divided into 2 groups: AA <48° and AA ≥48°. AA in the 480 patients who underwent balloon-expandable (BE) TAVR did not influence acute procedural success or short-term clinical outcome. In contrast, increased AA among the 102 patients who underwent self-expandable (SE) TAVR was found to significantly attenuate procedural success (area under the curve: 0.73; 95% confidence interval: 0.61 to 0.85; p = 0.008). The numerical cutoff for AA with the highest sum of sensitivity and specificity for device success was ≥48° (sensitivity 85%, specificity 61%). Moreover, patients whose AA was ≥48° were also associated with an increased need for a second valve and post-dilation, had increased fluoroscopy time and increased valve embolization, and had increased post-procedural paravalvular regurgitation greater than or equal to mild following SE TAVR. Major complications at 30 days, including mortality were similar between AA groups. Six-month mortality was also similar between both AA groups., Conclusions: Increased aortic root angulation adversely influences acute procedural success following SE but not BE TAVR. Because of these data, BE valves may be preferred when evaluating patients with high AA before TAVR., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the influence of body mass index (BMI) on short- and midterm outcomes following transcatheter aortic valve implantation (TAVI)., Background: Although obesity is a major risk factor for cardiovascular mortality, numerous studies reported a beneficial effect of obesity on survival in patients with cardiovascular disease and in patients after cardiac interventions. Moreover, all previous reports examining the relation between BMI and outcomes following TAVI have underscored the "obesity paradox" in these patients., Methods: During a 3 year period, 805 patients with severe aortic stenosis that underwent TAVI at our institute were evaluated. Based on baseline BMI, patients were classified as normal weight (18.5-24.9 kg/m(2) ), overweight (25.0-29.9 kg/m(2) ), or obese (≥30 kg/m(2) ). TAVI endpoints, device success, and adverse events were considered according to the Valve Academic Research Consortium (VARC)-2 definitions., Results: Obese patients were significantly younger, had higher prevalence of diabetes mellitus and chronic lung disease, and had lower prevalence of frailty. Device success was similar between the 3 groups. All-cause mortality up to 30 days was 2.9% (10/340) vs 4.5% (12/268) vs 0.5% (1/186) in patients with normal weight, overweight, and obesity, respectively (p = 0.048). In a multivariable model, overweight and obese patients had similar overall mortality compared to patients with normal weight., Conclusions: We found no evidence for the existence of an obesity paradox following TAVI. Correction for possible confounders such as frailty in the present cohort may explain the discrepancy between the current report and the previous reports that suggested a protective effect for increased BMI following TAVI. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Several clinical variables have been identified as predictors of clinical outcome after transcatheter aortic valve implantation (TAVI). Nonetheless, there is limited and contradictive data on the impact of diabetes mellitus (DM) on the prognosis of patients who undergo TAVI. We aimed to investigate the clinical characteristics and the early and midterm outcomes after TAVI according to DM status. From 802 consecutive patients who underwent TAVI, we compared 548 patients with no DM to 254 patients with diabetes (177 orally treated and 77 insulin treated). Patients with DM were younger had higher body mass index and incidence of coronary artery disease and lower incidence of frailty. Device success, 30-day mortality and major complications rates were similar between groups. One-year mortality was 12.1% for patient with DM and 12.2% for patients without DM (p = 0.91). In a multivariable regression analysis including age, body mass index, coronary artery disease and frailty, DM was associated with decreased overall survival. This was driven by increased overall mortality of the insulin-treated DM subgroup (hazard ratio 2.40, 95% CI 1.32 to 4.37; p <0.01). In conclusion, DM does not affect short-term mortality or rates of complications after TAVI. Insulin-treated DM, but not orally treated DM, is independently associated with death at midterm follow-up and therefore aggressive cardiovascular risk factor modification as well as intense glycemic control should be considered for patients with insulin-treated DM with severe aortic stenosis who undergo TAVI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

There are limited data on the effect of baseline B-type natriuretic peptide (BNP) on the outcome after transcatheter aortic valve implantation (TAVI). We investigated the influence of baseline BNP levels on the short-term and midterm clinical outcomes after TAVI. During a 3-year period, 780 patients with severe aortic stenosis underwent TAVI at our institute and had baseline BNP levels. We compared the high, mid, and low tertiles of BNP levels. TAVI end points, device success, and adverse events were considered according to the Valve Academic Research Consortium 2 definitions. Device success was significantly lower for patients with high BNP (98.1% vs 96.2% vs 91.9% for the low, mid, and high BNP tertiles, respectively; p = 0.003). All-cause mortality up to 30 days was 1.2% (3 of 260) versus 2.3% (6 of 260) versus 5% (13 of 260), respectively (p = 0.03). Six-month mortality rate was 4.1% (10 of 241) for the low BNP tertile, 5% (12 of 239) for the mid BNP tertile, and 17.1% (40 of 234) for the high BNP tertile (p <0.001). In the multivariate model, high tertile of baseline BNP was found to be significantly associated with all-cause mortality (hazard ratio 3.3, 95% confidence interval 1.64 to 6.48; p = 0.001). In conclusion, elevated BNP levels are associated with increased short-term and midterm mortality after TAVI. We recommend measurement of baseline BNP as part of risk stratification models for TAVI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The turtle plastron is composed of a keratinized epidermis overlying nine dermal bones. Its developmental origin has been controversial; recent evidence suggests that the plastral bones derive from trunk neural crest cells (NCCs)., Results: This study extends the observations that there is a turtle-specific, second wave of trunk NCC delamination and migration, after the original NCCs have reached their destination and differentiated. This second wave was confirmed by immunohistochemistry in whole-mounts and serial sections, by injecting DiI (1,1', di-octadecyl-3,3,3',3',-tetramethylindo-carbocyanine perchlorate) into the lumen of the neural tube and tracing labeled cells into the plastron, and by isolating neural tubes from older turtle embryos and observing delaminating NCCs. This later migration gives rise to a plastral ectomesenchyme that expresses NCC markers and can be induced to initiate bone formation., Conclusions: The NCCs of this second migration have properties similar to those of the earlier NCCs, but also express markers characteristic of cranial NCCs. The majority of the cells of the plastron mesenchyme express neural crest markers, and have osteogenic differentiation capabilities that are similar or identical to craniofacial ectomesenchyme. Our evidence supports the contention that turtle plastron bones are derived from a late emigrating population of cells derived from the trunk neural crest., (Copyright © 2013 Wiley Periodicals, Inc.)

Background & Objectives: The present study was carried out on stored rice variety PAU 201 in Punjab that was not permitted for milling and public distribution due to the presence of damaged grains at levels exceeding the regulatory limits of 4.75 per cent. The aim of the study was to determine fungal and aflatoxin contamination in the rice samples to assess hazard from the presence of damaged grains. Presence of iron in discoloured rice grains was also assessed., Methods: Stored samples of paddy of PAU 201 rice variety were collected from six districts of Punjab, milled and analysed for presence of fungal and aflatoxin contamination. Scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and Prussian blue staining was used to determine fungal spores and presence of iron, respectively., Results: Aflatoxin analysis of rice samples indicated that none exceeded the Food Safety and Standards (Contaminants, Toxins and Residues) Regulations, 2011 tolerance limit of 30 μg/kg and majority of the samples had levels <15 μg/kg. The proportion of damaged grains exceeding the limit of 5 per cent was observed in 85.7 per cent of the samples. SEM and Prussian blue staining and EDX analysis of black tipped and pin point damaged rice grains did not show presence of fungal structures and presence of iron., Interpretation & Conclusions: The results of the study indicated that the stored rice samples did not pose any health concern with respect to aflatoxin contamination as per the criteria laid down by the Food Safety and Standards Authority of India.

Objective: To study the clinical profile of patients with giant cell arteritis in Mumbai., Methods: From our database, patients with a diagnosis of giant cell arteritis (GCA) over a fifteen year period (January 1990 to December 2005) were included. Clinical manifestations, temporal artery biopsy, treatment, and follow-up data of these patients were analyzed., Results: Twenty one patients with GCA were identified. However, data were available only for 16 patients. The median age was 66.5 years (58-78 yrs) with male to female ratio of 1:1. The mean time from symptom onset to diagnosis was 5.18 months (0.5-24 months). Clinical manifestations included new onset headache (15), fever (9), weight loss (9), jaw claudication (9), polymyalgia rheumatica (5), visual disturbances (3), scalp nodule (1), temporal artery tenderness (11), tortuosity (9), and scalp tenderness (6). ESR was elevated in 15 patients with a median of 106.5 mm at 1 hr (25-135 mm/hr). Temporal artery biopsy was done in 11 patients and confirmed the diagnosis in 10 patients. Color doppler study of the temporal arteries (9 patients) revealed halo sign (indicating arterial wall edema) in 6 patients. Biopsy as per site by color doppler study was performed in 6 of these patients and was positive in 5. All patients had a good initial response to steroids, however, on follow up, 3 patients required addition of methotrexate. At a median follow up (n = 14) of 6 months (range 6-156), steroids were successfully stopped in 7 patients at 1 to 3 years interval. The disease relapsed in 1 patient. Of the remaining 7 patients, 2 were steroid dependent and 5 patients were doing well on low dose prednisolone., Conclusion: GCA, though uncommon in India, should be suspected in all elderly patients with a new onset headache, fever, jaw claudication, or high ESR. Color doppler sonography is a useful noninvasive method for the diagnosis of GCA and also helps to identify the site to biopsy. Most respond to steroid therapy while some need addition of steroid sparing agents.

Paget's disease is uncommon in Asians. We present 3 patients with varying manifestations. A 50 years old lady was detected to have raised alkaline phosphatase at a routine health check-up. Isoenzyme studies confirmed its bony origin. Bone scan revealed polyostotic disease. A 65 years old male patient with known Paget's disease of 6 years duration presented with pelvic girdle pain, progressive increase in alkaline phosphatase levels and worsening bone scan. A 45 years old male was admitted with chest pain. Cardiac evaluation was normal. Bone scan picked up a cough fracture in the left 7th rib and an incidental Paget's disease of the skull. All three had elevated markers of bone metabolism in the serum and urine. With monthly intravenous pamidronate there was significant improvement in the bone markers and follow-up bone scans.

Immunosuppressive therapy related secondary haematologic malignancy is well reported. A 52 years lady with established rheumatoid arthritis developed reactive amyloidosis. This was initially treated with colchicine and cyclophosphamide and later with chlorambucil. Ten months after stopping chlorambucil she developed pancytopenia and vitamin B12 deficient megaloblastic anaemia. The pancytopenia was refractory to vitamin B12 supplements and a repeat bone marrow confirmed myelodysplasia (FABI RAEB-T). Within three weeks of this diagnosis she evolved into acute myeloid leukaemia and expired due to refractory thrombocytopenia and uncontrolled bleeding. This case stresses the need for long term follow up of RA patients treated with alkylating agents.

A 60 year old diabetic was admitted with the history of low grade fever and weight loss of six weeks duration. After investigations, he was detected to have bilateral adrenal masses which on biopsy proved to be due to histoplasmosis. He was treated with itraconazole and made complete recovery.

Opportunistic infections in immunocompromised patients are common. We report the case of a 63 year old female patient with dermatomyositis who while on oral steroids developed nocardial infection of the lung and pseudomonas infection of the tongue simultaneously. Nocardial infections are not very commonly seen in patients with dermatomyositis. Pseudomonas infection of the tongue is a rarity. We report this case for its rarity as regards the type and site of infections and review the relevant literature.

The case of a research worker who accidentally injected herself with Freund's Complete Adjuvant (FCA) in the right forearm is reported. This resulted in a serious granulomatous inflammation of the hand an forearm. She was treated with corticosteroids and chloroquine with good result. The course of this reaction and the hazards of injection with FCA are emphasised and the relevant literature reviewed.

We report a case of a 14 year old girl with SLE who developed neurological involvement in the form of posterior internuclear ophthalmoplegia (pINO). An MRI showed lesion involving pons which corroborated with the pINO.

The case of a 40 year old female patient of SLE who developed fatal neuroleptic malignant syndrome following administration of serenase (haloperidol) is reported. Relevant literature has been reviewed.

An elderly female presented with a systemic febrile illness and acute polyarthritis as the first manifestation of gout. She improved dramatically with anti-inflammatory therapy.

Cytotoxic therapy, especially with cyclophosphamide in the dose 8-20 mg/kg used as intermittent pulses, has been shown to improve both patient and renal survival in systematic lupus erythematosus (SLE), but to date there is no cure for the disease. Owing to the paucity of recognisable clones, the rationale and goal of cytotoxic immunosuppressive therapy in the treatment of immune-mediated diseases as against malignancies is to suppress the aberrant inflammation and immune-mediated reactions responsible for tissue damage, without dangerously suppressing the normal host defence mechanism(s). We report the case of a patient suffering from SLE with nephritis who has remained in sustained remission over the past 8 years without any maintenance therapy following an accidental administration of a single dose of 5000 mg of intravenous cyclophosphamide (44.2 mg/kg body weight). The patient recovered fully from pancytopenia following the injection. Presently, she is asymptomatic and working gainfully. Her laboratory parameters including blood counts, urine analysis, FANA and anti-dsDNA have reverted to normal. Cyclophosphamide in the dose of 30-160 mg/kg has been safely and effectively used in various neoplastic conditions with the aim of destroying every possible tumour cell. The experience of the present case suggests that such an approach may be applicable to SLE.

In a retrospective analysis of 146 systemic lupus erythematosus (SLE) patients seen over a 5 year period, 17 patients of tuberculosis (TB) were identified yielding a prevalence rate of 11.6%. The median duration of SLE was 12 months (range 2-96 months) and 12/17 patients had disease activity score of more than five. The median duration of steroid treatment was 12 months (range 0-96 months) and the median cummulative dose of steroid was 7.75 gms (range 0-22.1 gms). Pulmonary TB (miliary-5, nonmiliary infiltrates-7 and pleural effusion-2) was the commonest type and there was an average diagnostic delay of approximately 1 month. While, majority of the patients responded adequately to treatment, 1 patient had a relapse and 1 expired due to a combination of active lupus and disseminated TB. Only 1 patient had received prophylactic isoniazid.

Fourteen patients undergoing total knee replacement for the arthritic conditions of the knee were evaluated by ultrasonography (USG) prior to surgery. USG findings (synovium, fluid, femoral cartilage, cyst and loose bodies) were compared with surgical findings. USG and surgical findings matched for synovial pathology in 57%, for presence fluid in 71% and for cartilage damage in 45%. Loose bodies and cyst present in one patient was not picked up by USG. Baker's cyst was detected in one patient.

Autoimmune hepatitis (AIH) is characterised by the presence of periportal hepatitis coupled with the presence of autoantibodies in the serum. We report our experience with 10 cases (females--8, males--2) who presented to the rheumatology clinic with either articular or extra-articular manifestations. Three patients (1 SLE, 1 Sjogren's and 1 RA), satisfied the criteria for an underlying rheumatic disease (secondary AIH) while, others had primary AIH. Median duration of hepatic involvement was 6 months and the varied presentations were noted. Articular disease ranged from arthralgias, palindromic arthritis to persistent non-erosive/non-deforming arthritis (Jaccoud's arthritis). Autoimmune thrombocytopenia was seen in 2 and autoimmune hypo and hyperthyroidism were seen in 3 patients each. Anti-nuclear antibody was positive in 9/10 (6 with speckled pattern and 3 with homogenous pattern) and anti-mitochondrial antibodies were positive in three. Hepatitis C virus (HCV) markers were positive in 1, who probably had viral hepatitis with dominant autoimmune features. All have been started on steroids (5 patients--1 mg/kg dose, 1 patient--0.5 mg/kg dose and 3 patients--0.25 mg/kg dose). The HCV positive patient was on a low dose steroid (0.25 mg/kg) and interferron treatment was contemplated before she was lost to follow up. Four patients are also on azathioprine in the dose of 2 mg/kg/day. Of the 6 patients who are under regular follow up, the liver parameters have normalised in 5 and one showed hypoalbuminaemia with normal enzyme levels at the last follow up.