The impact of vascular access location on pulmonary arterial pressure in chronic kidney disease patients undergoing hemodialysis.

BACKGROUND AND AIM: It is feared that among chronic kidney disease patients undergoing hemodialysis, arteriovenous fistula (AVF) itself could contribute to pulmonary hypertension (PH). The impact of AVF location on PH is yet to be assessed. We hypothesize that patients with proximal AVF have higher access blood flow and hence higher pulmonary arterial systolic pressure (PASP) than those with distal AVF. We aimed to compare the PASP between patients with proximal and distal AVF. METHODS: In this cross-sectional study, PASP was estimated using Doppler echocardiography and blood flow in the AVF was assessed by Doppler ultrasound. PASP was modeled by multivariate linear regression. AVF location was the primary exposure of interest. RESULTS: Out of 89 patients undergoing hemodialysis, 72 (81%) had PH defined as PASP >35 mmHg. The mean blood flow in proximal and distal AVF was, respectively, 1240 and 783 mL/min (mean difference 457 mL/min, p < 0.001). Mean PASP in patients with proximal AVF was 16.6 mmHg higher than those with distal AVF (p < 0.001, 95% CI 8.3-24.9). There was a positive correlation between access blood flow and PASP (r = 0.28, p = 0.007). If access blood flow was included as a covariate in the multivariate model, the association between AVF location and PASP ceased to exist. CONCLUSION: Patients with proximal AVF have a significantly higher PASP than those with distal AVF, and this could be attributed to the higher blood flow in proximal AVF compared to distal AVF.

Fulminant onset COVID-19: predictors and outcome.

PURPOSE: During COVID-19 infection, organ dysfunction such as respiratory failure tends to occur towards the second week of illness; however, in a subset, there may be rapid onset of organ dysfunction as early as symptom onset. We define fulminant onset COVID-19 as rapid onset of organ dysfunction such as acute respiratory failure, acute kidney injury, acute encephalopathy or shock within 4 days of symptom onset. Fulminant onset COVID-19 has not yet been systematically studied. We aimed to identify predictors and prognosis of fulminant onset COVID-19. METHODS: This retrospective study was carried out on patients admitted to a single referral hospital in South India between June 2020 and January 2022. Patients were categorised into fulminant and non-fulminant onset COVID-19. Candidate predictors for fulminant onset were chosen by an intuitive approach and analysed using logistic regression. Then, the outcome of fulminant onset COVID-19 at 30 days was studied. RESULTS: Out of 2016 patients with confirmed COVID-19, 653 (32.4%) had fulminant onset COVID-19. Age>60 years (a-OR 1.57, 95% CI 1.30 to 1.90, p<0.001), hypertension (a-OR 1.29, 95% CI 1.03 to 1.61, p=0.03) and immune-suppressed state (a-OR 5.62, 95% CI 1.7 to 18.7, p=0.005) were significant predictors of fulminant onset COVID-19. Complete vaccination lowered the odds of fulminant onset COVID-19 significantly (a-OR 0.61, 95% CI 0.43 to 0.85, p=0.004). At 30 days, the fulminant onset COVID-19 group had higher odds of mortality and need for organ support. CONCLUSION: Fulminant onset COVID-19 is not uncommon and it carries poor prognosis and deserves recognition as a distinct phenotype of COVID-19.

Quantum-Quantum and Quantum-Quantum-Classical Schemes for Near-Gap Excitations with Projection-Based-Embedded GW-Bethe-Salpeter Equation.

We present quantum-quantum and quantum-quantum-classical schemes based on many-body Green's functions theory in the GW approximation with the Bethe-Salpeter equation (GW-BSE) employing projection-based-embedding (PbE). Such approaches allow defining active and inactive subsystems of larger, complex molecular systems, with only the smaller active subsystem being explicitly treated by GW-BSE offering significant computational advantages. However, as PbE can modify the single-particle states in the Kohn-Sham (KS) ground state calculation and screening effects from the inactive region are not automatically included in GW-BSE, results from such PbE-GW-BSE calculations can deviate from a full-system reference. Here, we scrutinize in detail, e.g., the individual and combined effects of different choices of active regions, the influence of omitting the screening from the inactive region, and strategies for basis set truncation on frontier orbital and near-gap electron-hole excitation energies. As prototypical systems, we consider a diketopyrrolopyrrole bicyclic ring including side-chains, a polarity-sensitive dye (prodan) in aqueous environment, and a π-stacked dimer of benzene and tetracyanoethylene in water, respectively, covering a variety of excitation characters in molecular systems with complex chemical environments and photoinduced processes. Our results suggest that to obtain agreement of approximately 0.1 eV between near-gap excitation energies from embedded and full calculations, the active region should be chosen based on the Mulliken population of the full highest-occupied molecular orbital and that careful benchmarking should be done on the KS level before the actual GW-BSE steps when basis set truncation is used. We find that PbE-GW-BSE offers significant reductions in computation times and, more importantly, memory requirements, making calculations for considerably larger systems tractable.

Effect of Solvent Removal Rate and Annealing on the Interface Properties in a Blend of a Diketopyrrolopyrrole-Based Polymer with Fullerene.

We study the effect of solvent-free annealing and explicit solvent evaporation protocols in classical molecular dynamics simulations on the interface properties of a blend of a diketopyrrolopyrrole (DPP) polymer with conjugated substituents (DPP2Py2T) and PCBM[60]. We specifically analyze the intramolecular segmental mobility of the different polymer building blocks as well as intermolecular radial and angular distribution functions between donor and acceptor. The annealing simulations reveal an increase of the glass-transition temperature of 45 K in the polymer-fullerene blend compared to that of pure DPP2Py2T. Our results show that the effective solvent evaporation rates at room temperature only have a minor influence on the segmental mobility and intermolecular orientation, characterized in all cases by a preferential arrangement of PCBM[60] close to the electron-donating substituents in DPP2Py2T. In contrast, solvent-free annealing from a liquid yields clustering of the fullerene close to the electron-withdrawing DPP, generally considered to be detrimental for application in organic solar cells. We find that the difference can be attributed to differences in the behavior of 2-hexyldecyl side-chains, which collapse toward DPP when solvent is explicitly removed, thereby blocking access of PCBM[60].

Twenty Years of Insulin Gla-100: A Systematic Evaluation of Its Efficacy and Safety in Type 2 Diabetes Mellitus.

INTRODUCTION: This systematic review aims to present the current evidence base with respect to the initiation and intensification of insulin therapy with glargine 100 U/mL (Gla-100) compared to other insulins in people with type 2 diabetes mellitus (T2DM). METHODS: A systematic literature search of PubMed (MEDLINE), EMBASE, and the Cochrane Central Register of controlled clinical trials databases was performed to identify studies published up to September 30, 2020 that compared the effects of Gla-100 to that of other insulin regimens in people with T2DM. Relevant information pertaining to the predefined outcomes of interest was extracted. Glycated hemoglobin (HbA1c) change and response rates along with overall hypoglycemia incidence were the primary efficacy and safety outcomes of interest. RESULTS: Seventy-nine studies (63 interventional and 16 non-interventional) in which Gla-100 was either initiated in previously insulin-naïve patients (n = 57) or used in an intensified regimen (n = 22) were identified and evaluated. In insulin-naïve patients, most studies demonstrated that Gla-100 was significantly better compared with premixed insulins and similar compared with neutral protamine Hagedorn (NPH) insulin, second-generation basal insulins, co-formulations, and other first-generation basal insulins in terms of the primary efficacy parameters. Overall hypoglycemia risk with Gla-100 was significantly lower compared with NPH, premixed, coformulation, and other first-generation basal insulins and significantly higher compared with second-generation basal insulins. In studies with intensified regimens, efficacy outcomes with Gla-100 were significantly better compared with insulin detemir (IDet); similar compared with NPH, second-generation basal insulins, co-formulations; and with premixed insulins. In these studies, overall hypoglycemia risk with Gla-100 was significantly lower compared with IDet and comparable to NPH, premixed insulins, co-formulations, and second-generation basal insulins. In addition, most intensification studies also revealed a significantly lower risk of nocturnal hypoglycemia with Gla-100-based regimens versus NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins. CONCLUSIONS: The evidence presented in this review suggests that Gla-100 is an effective option for both insulin initiation and intensification strategies used in the management of T2DM.

Whole lung irradiation as a novel treatment for COVID-19: Final results of the prospective randomized trial (WINCOVID trial).

BACKGROUND AND PURPOSE: The ability of low dose radiotherapy (LDRT) to control the unprecedented cytokine release associated with COVID-19 pathogenesis has been an area of widespread research since the COVID pandemic. It has not been studied adequately whether the anti-inflammatory effect of LDRT provides additional benefit when used concurrently with steroids amongst other standard pharmacologic therapy. MATERIAL AND METHODS: 51 RT-PCR positive COVID-19 patients were recruited between November 2020 and July 2021. 34 patients were allotted to receive 0.5 Gy single session LDRT along with standard pharmacologic therapy while 17 patients received standard pharmacologic therapy alone. All had SpO2 <94% on room air, respiratory frequency >24/min and SpO2/FiO2 (SF) ratio between >89 but <357. All patients underwent a baseline CT scan. They were followed up for 28 days during when serial SF ratio, blood biomarkers (CRP, Serum ferritin, IL-6), Absolute lymphocyte count (ALC), repeat CT scan were performed at pre-defined time points. RESULTS: LDRT showed a statistically significant early improvement in oxygenation, an early time to clinical recovery, early hospital discharge and better radiological resolution compared to control group. There was no statistically significant difference between the two groups with respect to ALC or blood biomarkers at any of the measured time points. The 28-day mortality rate did not show statistically significant difference between the two groups. CONCLUSION: LDRT can be considered for selected oxygen-dependent moderate to severe COVID-19 patients for rapid relief of respiratory distress. It can be safely combined with standard pharmacologic treatment in such patients for added clinical benefit.

Pattern recognition of high-resolution computer tomography (HRCT) chest to guide clinical management in patients with mild to moderate COVID-19.

AIM: To describe the distribution of lung patterns determined by High Resolution Computed Tomography (HRCT) in COVID patients with mild and moderate lung involvement and outcomes after early identification and management with steroids and anticoagulants. MATERIAL AND METHODS: A cross sectional study of COVID-19 patients with mild and moderate lung involvement presenting at 5 healthcare centres in Trichy district of South TamilNadu in India. Patients underwent HRCT to assess patterns and severity of lung involvement, Inflammatory markers (LDH/Ferritin) and D-Dimer assay and clinical correlation with signs and symptoms. Patients were assessed for oxygen, steroid and anticoagulant therapy, clinical recovery or progression on follow up and details on mortality were collected. The RSNA, Fleischer Society guidelines and CORADS score was used for radiological reporting. New potential classification of patterns of percentage of lung parenchyma involvement in Covid patients is being suggested. RESULTS: The study included 7,340 patients with suspected COVID and 3,963 (53.9%) patients had lung involvement based on HRCT. RT PCR was positive in 74.1% of the CT Positive cases. Crazy Pavement pattern was predominant (n = 2022, 51.0%) and Ground Glass Opacity (GGO) was found in 1,941 (49.0%) patients in the study. Severe lung involvement was more common in the Crazy Pavement pattern. Patients with GGO in moderate lung involvement were significantly more likely to recover faster compared to Crazy Pavement pattern (P value <0.001). CONCLUSION: HRCT chest and assessment of lung patterns can help triage patients to home quarantine and hospital admission. Early initiation of steroids and anticoagulants based on lung patterns can prevent progression to more severe stages and aid early recovery. HRCT can play a major role to triage and guide management especially as RT PCR testing and results are delayed for the benefit of patients and in a social cause to decrease the spread of the virus.

Whole lung irradiation as a novel treatment for COVID-19: Interim results of an ongoing phase 2 trial in India.

BACKGROUND AND PURPOSE: The main cause of death in COVID-19 pneumonia is acute respiratory distress syndrome which is preceded by massive cytokine release. Low-dose radiation therapy (LDRT) has anti-inflammatory and immunomodulatory effects that can interfere with the inflammatory cascade, reducing the severity of associated cytokine release. MATERIAL & METHODS: 25 patients with RT-PCR proven COVID-19 pneumonia were enrolled between November 2020 and May 2021. All patients had SpO2 < 94 % on room air, respiratory frequency > 24/min and SpO2/FiO2 ratio (SF ratio) of >89 but <357. Patients were treated according to standard COVID-19 management guidelines along with single fraction LDRT of 0.5 Gy to bilateral whole lungs within 10 days of symptom onset and 5 days of hospital admission. RESULTS: LDRT was well tolerated by all patients. There was a statistically significant improvement in oxygenation as given by the SF ratio between pre-RT and day 2 (p < 0.05), day 3 (p < 0.001) and day 7 (p < 0.001) post RT. Demand for supplemental oxygen showed statistically significant reduction between pre-RT and day 2 (p < 0.05), day 3 (p < 0.001), day 7 (p < 0.001) post RT. 88 % patients attained clinical recovery within 10 days post LDRT and median time to hospital discharge from day of LDRT was 6 days. Three patients deteriorated and died. CONCLUSION: As per our initial experience, LDRT appears to be a promising modality of treatment with rapid relief of respiratory distress in selected patients with moderate to severe COVID-19 pneumonia. This translates to early clinical recovery and hospital discharge in the selected patient group.

Development and Testing of an All-Atom Force Field for Diketopyrrolopyrrole Polymers with Conjugated Substituents.

We develop an all-atom force field for a series of diketopyrrolopyrrole polymers with two aromatic pyridine substituents and a variable number of π-conjugated thiophene units in the backbone (DPP2PymT), used as donor materials in organic photovoltaic devices. Available intrafragment parameterizations of the individual fragment building blocks are combined with interfragment bonded and nonbonded parameters explicitly derived from density functional theory calculations. To validate the force field, we perform classical molecular dynamics simulations of single polymer chains with m = 1, 2, 3 in good and bad solvents and of melts. We observe the expected dependence of the chain conformation on the solvent quality, with the chain collapsing in water, and swelling in chloroform. The glass-transition temperature for the polymer melts is found to be in the range of 340-370 K. Analysis of the mobility of the conjugated segments in the polymer backbone reveals two relaxation processes: a fast one with a characteristic time at room temperature on the order of 10 ps associated with nearly harmonic vibrations and a slow one on the order of 100 ns associated with temperature-activated cis-trans transitions.

A male patient with right-sided thoracic kidney, diabetes mellitus, hearing loss and renal dysfunction.

A 48-year-old man with diabetes mellitus and hypertension was found to have a thoracic right-sided ectopic kidney with a sensorineuronal hearing loss and tubular abnormalities such as hyponatremia, hypokalemia, metabolic alkalosis with microalbuminuria. He was treated with ACEI and sodium and potassium supplements. However, this only partially corrected his metabolic abnormalities.

Management of chronic allograft dysfunction by switch over to rapamycin.

The aim of this study was to evaluate the efficacy of conversion from calcineurin inhibitors (CNI)-based to a rapamycin-based immunosuppressive regimen in renal transplant recipients who had allograft dysfunction, in a South Indian population. We analyzed the results of 75 (19.5%) of the 398 renal transplants performed over a five-year period from 2002 to 2007, who were converted from a CNI-based immunosuppression to rapamycin including patients with chronic allograft dysfunction, chronic allograft injury and malignancy. The data analyzed included serial rapamycin levels, serum creatinine, eGFR by nankivel formula, lipid profile, hemoglobin and serum potassium levels. Statistical analysis was performed using student's t test and the Kaplan Meir survival curve was used to predict probability of survival among patients on rapamycin. The mean age of the study patients was 39.6 + or - 12.2 yrs and there was a male predominance (74.6%). Diabetic nephropathy was the predominant cause (36%) of end-stage renal disease (ESRD). Statistical analysis revealed a significant improvement in GFR of 14.6 mL/min and decrease in potassium by 0.7 mmol/L after initiation of rapamycin. There were no significant differences in terms of lipid profile, platelet count, hemoglobin and urine albumin levels. Rapamycin was discontinued in one patient due to hypokalemic nephropathy and in another patient due to delayed wound healing. To our knowledge, this is the first study to provide information on the conversion from a CNI to rapamycin-based immunosuppression in a cohort of Indian renal transplant recipients. In conclusion, the findings of our study confirm that rapamycin-based immunosuppressive regimen improves renal function and graft survival with minimal side effects, in comparison to CNI-based immunosuppression.

C-Reactive protein, a valuable predictive marker in chronic kidney disease.

The aim of this study was to look for correlation between the markers for malnutrition and inflammation, and atherosclerosis in predialysis chronic kidney disease (CKD) patients. This observational study involved 100 predialysis patients (age 57 +/- 12 years) from the out-patient and in-patient departments over a span of two years. Informed consent was obtained from all the study patients. Highly sensitive C-reactive protein (hsCRP) was assayed as a marker of chronic inflammation. Nutritional status was assessed using serum albumin and body mass index (BMI). Clinical and laboratory data were collected and a carotid doppler study was performed using duplex ultrasonography method to look for carotid artery stenosis. Renal function was assessed by calculating the estimated glomerular filtration rate (GFR) by the MDRD-2 formula. These data were later analyzed using descriptive statistics, Chi-square test and the students' t test. The mean GFR was 28.3 +/- 16.4 mL/min/1.73m 2 . The mean value of CRP was 14.3 +/- 11.4 mg /L. Sixty-seven percent of patients had elevated CRP (> 6 mg/L) levels. Patients with higher CRP levels showed lower mean serum albumin levels (3.2 +/- 0.7 gm/dL) (P < 0.01). Only three patients had evidence of hemodynamically significant carotid disease (lumen diameter < 50%) with no statistical significance. Low serum albumin levels were associated with low hemoglobin levels (< 10 gm/dL), low GFR and presence of diabetes mellitus. Our results indicate that a high degree of inflammation and malnutrition exists in predialysis patients as seen by high CRP values and low serum albumin levels. Synergism of these factors could contribute to atherosclerosis in CKD apart from the classic risk factors. To our knowledge, this is the first study, which has compared these markers of inflammation in predialysis patients in developing countries.