Fabrication of a New Rationally Designed Mussel-Inspired Cationic Amphiphilic Terpolymer to Enhance the Separation and Anti-Fouling Performance of Membranes.

Polyvinylidene fluoride (PVDF) membrane-based systems for treating oily wastewater are prone to fouling. Herein, we introduced a novel mussel-inspired cationic amphiphilic terpolymer consisting of monomers N,N-diallyldimethylammonium chloride (DADMAC), N,N-diallyltetradecan-1-ammonium chloride (DTDAC), and mussel-inspired N,N-diallyldopamine hydrochloride (DADAHC) to improve the performance and characteristics of the PVDF membranes for oil-in-water emulsion separations. The cationic terpolymer, poly(DADMAC-co-DTDAC-co-DADAHC), shortened as PDDD, was synthesized in excellent yields via free radical polymerization and has good compatibility with the PVDF owing to the presence of hydrophobic long alkyl chains in DTDAC. The presence of dopamine motifs helps stabilize the PDDD-PVDF membrane by chelating with Fe3+ ions. The water contact angle on the PDDD-incorporated PVDF membranes was reduced from 87.6 to 54.6°, demonstrating improved hydrophilicity than pristine PVDF (M-0). The incorporation of PDDD into the PVDF improved the separation efficiencies of the membrane, which reached up to 99% while treating the oil-in-water emulsions. Incorporating PDDD into PVDF has significantly enhanced the anti-fouling characteristics of the membranes, which are indicated by their remarkable flux recovery ratio (FRR) (up to 92%). The hydrophobic and hydrophilic groups worked synergetically to enhance the performance of the fabricated membrane.

Stimuli-Responsive Macromolecular Architecture by Butler Cyclopolymerizations: Synthesis and Applications.

This article reviews the synthesis of polyzwitterions (PZs) (poly-carboxybetaines, -phosphonobetaines, and -sulfobetaines) having multiple pH-responsive centers. The synthesis follows the Butler cyclopolymerization protocol involving a multitude of diallylammonium salts and their copolymerization with SO2 and maleic acid. The PZs have been transformed into cationic-, anionic-polyelectrolytes, and polyampholytes under the influence of pH. Particular attention is given to the application of these polymers as antiscalants, mild steel corrosion inhibitors, components in constructing Aqueous Two-Phase Systems (ATPSs), and membrane modifiers. The ATPSs could be used to separate various biomolecules, including proteins. Many amphiphilic polymers incorporating a few mol % hydrophobic monomers have shown enhanced viscosities and could be suitable for applications in oil fields. The progress of applying Butler cyclopolymerization in reversible addition-fragmentation chain transfer (RAFT) chemistry has been discussed. Future works are expected to focus on RAFT cyclopolymerization to construct block copolymers.

SARS-CoV-2 Exposure from Health Care Workers to Infants: Effects and Outcomes.

OBJECTIVE: This study aimed to evaluate the risk and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from positive health care workers (HCW) to infants in the neonatal intensive care unit (NICU) and the postnatal ward. STUDY DESIGN: We conducted a retrospective analysis of infants in NICU and the postnatal ward postexposure to a COVID-19 positive HCW between May 1 and July 31, 2020. HCW had the detection of SARS-CoV-2 after being symptomatic. Infants exposed to these HCW were tested for SARS-CoV-2 and were classified as confirmed positive when test was positive 24 hours after exposure; confirmed negative when test was negative with no escalation of respiratory support provided; and probable if test was negative. However, infant required escalation of respiratory support. Infants were followed at 14 days postexposure then at the end of the study period for admitted infants. RESULTS: A total of 31 infants were exposed to SARS-CoV-2 positive HCWs (42 exposure incidences). The median age at exposure was 21 days. None of the infants was confirmed positive. Nine infants were classified as probable cases of whom five infants with underlying chronic illnesses died, two were discharged home, and two were still admitted. Of the 22 confirmed negative cases, 15 were discharged and were well on follow-up, and 7 were still admitted. CONCLUSION: No active transmission of infection from infected HCW to admitted infants was identified. Although some infants had respiratory escalation postexposure none were confirmed positive. Adhering to personal protective equipment by HCW or low susceptibility of infants to SARS-CoV-2 infection may explain the lack of transmission. KEY POINTS: · There are no reported cases of transmission of SARS-CoV-2 infection from infected HCW to infants admitted to the NICU in our study.. · Adherence to personnel protective equipment is important to prevent transmission of SARS-CoV-2. · When an infant is exposed to a HCW who is positive for SARS-CoV-2 and has escalation of respiratory support, SARS-CoV-2 as a cause should be investigated.

Robot assisted radical prostatectomy in fit older patients compared to a standard population: Clinical characteristics, surgical, oncological and functional outcomes.

INTRODUCTION: To compare robotic assisted radical prostatectomy (RARP) in well-selected older patients with clinically localized prostate cancer, compared to a younger population. Primary endpoint was perioperative outcomes comparison and secondary endpoint were oncological and functional outcomes comparison to a younger population. METHODS: Single tertiary center cohort of consecutive patients treated with RARP (2017-2020) with retrospective analysis. Patients were classified by age in two groups: <75: control group (CG) and ≥75: study group (SG). Patients aged ≥75 had a comprehensive geriatric assessment (CGA) and only patients classified Balducci ≤2 were admitted to surgery. RESULTS: Two hundred and sixty-nine patients were included, 56 in SG and 213 in CG. Median follow-up was 9.8 months. Univariate analysis showed no statistically significant (SS) difference between the groups for patients' characteristics (PSA, digital rectal examination -DRE- and biopsy Gleason Score), perioperative data (operative time, hospitalization length, transfusions rate, immediate complications, Clavien-Dindo complications, 30-days re-interventions and 30-days re-hospitalisation), oncological (TNM, margins, extraprostatic extension, postoperative PSA, BCR, metastases, overall survival -OS- and cancer specific survival -CSS-) and functional outcomes. Median perioperative blood loss was lower in the SG: 200.00 cc IQR [100.00, 300.00] vs 200.00cc IQR [100.00, 400.00] in the CG (P<0.05). A multivariate regression considering age>75, DRE, GS, PSA, cardiovascular history and diabetes showed none of variables associated with early BCR. Limitations are retrospective design, small number of patients and short follow-up. CONCLUSIONS: RARP shows similar perioperative, oncologic and functional outcomes for older patients selected by a CGA when compared to younger patients. The SG shows a minor perioperative bleeding. LEVEL OF EVIDENCE: IV.

THE STUDY OF VDR FOKI RS2228570 SNP IN AUTOIMMUNE THYROIDITIS.

Autoimmune thyroid disease (AITD) is a common organ-specific autoimmune disease. A strong influence of genetic and epigenetic modifications has been demonstrated to take part in the development and progression of autoimmune thyroid diseases. The linkage between the Vitamin D receptor (VDR) polymorphism and several autoimmune disorders, including the AITD. In this article, we aim to investigate the Frequency of VDR Fokl (rs2228570) genotypes (CC, CT, TT) and alleles (C,T) in autoimmune thyroiditis. The investigation of VDR Fokl (rs2228570) was conducted on 150 samples (control (75 healthy women) and diseased women (75 diseased with autoimmune thyroiditis)) patients from the Adjara (Georgia) Population. It also examined some clinical and laboratory characteristics of the study population. Autoimmune thyroiditis's disease was diagnosed by measuring blood antibodies, determining the level of thyroperoxidase, and conducting an ultrasound examination. Anti-TPO and TSH were studied using the ELISA method. The genomic DNA was extracted from the peripheral blood. The polymerase chain reaction was evaluated to examine the VDR Fokl rs2228570 SNP polymorphism. According to VDR Fokl (rs2228570) genotypes (CC; CT, TT) frequency, in the control group, the Frequency of CC-genotype is 48%, CT-heterozygous genotype is 29.33%, and TT-genotype is 22.67%; in the diseased population, the Frequency of CC-genotype is 57.33%, CT-genotype is 34.67%, and TT-genotype is 8%. According to VDR Fokl (rs2228570) alleles (C, T), the Frequency of the C-allele is high, and the Frequency of the T-allele is low in both populations. The Frequency of the CC and CT genotypes of VDR Fokl (rs2228570) is high in the population with autoimmune thyroiditis compared to the control group; the TT genotype is relatively low in the population suffering from autoimmune thyroiditis; According to VDR Fokl (rs2228570) alleles (C, T), the Frequency of C-allele is high both population.

Hybrid support vector regression and crow search algorithm for modeling and multiobjective optimization of microalgae-based wastewater treatment.

Microalgae-based wastewater treatment (and biomass production) is an environmentally benign and energetically efficient technique as compared to traditional practices. The present study is focused on optimization of the major treatment variables such as temperature, light-dark cycle (LD), and nitrogen (N)-to-phosphate (P) ratio (N/P) for the elimination of N and P from tertiary municipal wastewater utilizing Chlorella kessleri microalgae species. In this regard, a hybrid support vector regression (SVR) technique integrated with the crow search algorithm has been applied as a novel modeling/optimization tool. The SVR models were formulated using the experimental data, which were furnished according to the response surface methodology with Box-Behnken Design. Various statistical indicators, including mean absolute percentage error, Taylor diagram, and fractional bias, confirmed the superior performance of SVR models as compared to the response surface methodology (RSM) and generalized linear model (GLM). Finally, the best SVR model was hybridized with the crow search algorithm for single/multi-objective optimizations to acquire the global optimal treatment conditions for maximum N and P removal efficiencies. The best-operating conditions were found to be 29.3°C, 24/0 h/h of LD, and 6:1 of N/P, with N and P elimination efficiencies of 99.97 and 93.48%, respectively. The optimized values were further confirmed by new experimental data.

[Medico-economic evaluation of the impact of measures to adapt to the switch to surgery robot-assisted in urology]. / Évaluation médico-economique de l'impact de mesures d'adaptation au virage de la chirurgie robot-assistée en urologie.

INTRODUCTION: The development of robot-assisted urological surgery is held back by the lack of robust medico-economic analyses and their heterogeneity. We conducted a medico-economic study to evaluate the implementation of measures to optimize the transition to robotic surgery. METHOD: We carried out a single-center, controlled study from the point of view of the public healthcare establishment for 4 years. Economic data collection was based on a micro-costing method and revenues from stay-related groups. Clinical data corresponded to mean lengths of stay, operating duration, complications and stays in intensive care. The measures to optimize the transition to robotic, implemented mid-study period, enabled before/after comparison. RESULTS: Altogether, 668 patients undergoing robotic surgery were included. Robotic activity increased significantly from periods 1 to 2 to 256% (P=<0.001) as did the overall proportion of robotic by 45% to 85% (P=<0.001). The mean lengths of stay fell significantly, 6.8 d vs. 5.1 d (P<0.001). Costs and revenues increased significantly, resulting in a persistent deficit for the activity €226K vs. €382K (P=<0.001). With increased volume of activity, the deficit per operation and the cost per minute of robotic operating room fell significantly, €3,284 vs. €1,474/procedure (P=<0.001) and €27 vs €24/min (P=<0.029), tending towards a break-even point (=zero deficit) at 430 operations per year. CONCLUSIONS: Robotic-assisted surgery can be significantly optimized by implementing measures for the robotic turn to reach a break-even point at 430 operations per year. A better multidisciplinary case mix could lower the break-even volume of activity in short term. LEVEL OF EVIDENCE: 3.

Neuronal Activity of Pallidal Versus Cerebellar Receiving Thalamus in Patients with Cervical Dystonia.

Cervical dystonia (CD) is a movement disorder characterized by a stereotyped pattern of involuntary turning or tilting of the head, often combined with jerky or tremulous movements. Hypotheses for the origin of CD have traditionally focused on the basal ganglia, but the contemporary discussion has considered the potential role of altered cerebellar function. As basal ganglia and the cerebellum largely project to the different thalamic nuclei, alterations in pallidal versus cerebellar output could be reflected in the activity of these thalamic regions. In this study, we analyzed a unique historic database where the single-unit activity of pallidal and cerebellar receiving thalamic nuclei was measured en route to the mesencephalon. We compared the single-unit activity of pallidal and cerebellar receiving thalamic neurons in three groups of CD patients manifesting as pure dystonia, pure jerky head oscillations, and dystonia plus jerky head oscillations. We found that among different CD manifestations, the characteristics of neuronal firing, such as burst versus a single-spike pattern, vary in cerebellar thalamic receiving nuclei. The cerebellar receiving region in patients with jerky oscillations had single-spikes neurons primarily. Wherein the manifestation of CD did not influence pattern distribution in the pallidal receiving thalamic area. We also found increased neuronal firing rate correlated with strength of theta-band neuronal oscillations during muscle contractions associated with dystonia. These results demonstrate that the manifestations of CD, such as pure dystonia, pure jerky head oscillations, or dystonia and jerky head oscillations, determine the thalamic neuronal properties.

[Outcomes following the triage of patients for urological cancer and non-cancer surgery during Covid-19 pandemic peak]. / Évaluation des mesures de triages de la première vague pandémique Covid-19 pour sélectionner les patients à opérer pour cancers et urgences urologiques.

INTRODUCTION: Faced with the first wave of Covid-19 pandemic, guidelines for surgical triage were developed to free up healthcare resources. The aim of our study was to assess clinical characteristics and surgical outcomes of triaged patients during the first Covid-19 crisis. METHOD: We conducted a cohort-controlled, non-randomized, study in a University Hospital of south-eastern France. Data were collected prospectively from consecutive patients after triage during the period from March 15th to May 1st and compared with control data from outside pandemic period. Primary endpoint was intensive care unit (ICU) admissions for surgery-related complications. Rates of surgery-specific death, postponed operations, positive PCR testing and Clavien-Dindo complications and data from cancer and non- cancer subgroups were assessed. RESULTS: After triage, 96 of 142 elective surgeries were postponed. Altogether, 71 patients, median age 68 y.o (IQR: 56-75 y.o), sex ratio M/F of 4/1, had surgery, among whom, 48 (68%) had uro-oncological surgery. No patients developed Covid-19 pneumonia in the post-surgery period. Three (4%) were admitted to the ICU, one of whom died from multi-organ failure due to septic shock caused by klebsiella pneumonia following a delay in treatment. Three Covid-19 RT-PCR were done and all were negative. There was no difference in mortality rates or ICU admission rates between control and Covid- era patients. CONCLUSIONS: Surgery after triage during the first Covid-19 pandemic was not associated with worse short-term outcomes. Urological cancers could be operated on safely in our context but delays in care for aggressive genitourinary diseases could be life threatening. LEVEL OF EVIDENCE: 3.

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders.

Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event produces acute focal damage (e.g., stroke, trauma), impaired cerebellar function may be compensated for by other cerebellar areas or by extracerebellar structures (i.e., structural cerebellar reserve). In contrast, when pathological changes compromise cerebellar neuronal integrity gradually leading to cell death (e.g., metabolic and immune-mediated cerebellar ataxias, neurodegenerative ataxias), it is possible that the affected area itself can compensate for the slowly evolving cerebellar lesion (i.e., functional cerebellar reserve). Here, we examine cerebellar reserve from the perspective of the three cornerstones of clinical ataxiology: control of ocular movements, coordination of voluntary axial and appendicular movements, and cognitive functions. Current evidence indicates that cerebellar reserve is potentiated by environmental enrichment through the mechanisms of autophagy and synaptogenesis, suggesting that cerebellar reserve is not rigid or fixed, but exhibits plasticity potentiated by experience. These conclusions have therapeutic implications. During the period when cerebellar reserve is preserved, treatments should be directed at stopping disease progression and/or limiting the pathological process. Simultaneously, cerebellar reserve may be potentiated using multiple approaches. Potentiation of cerebellar reserve may lead to compensation and restoration of function in the setting of cerebellar diseases, and also in disorders primarily of the cerebral hemispheres by enhancing cerebellar mechanisms of action. It therefore appears that cerebellar reserve, and the underlying plasticity of cerebellar microcircuitry that enables it, may be of critical neurobiological importance to a wide range of neurological/neuropsychiatric conditions.

[Assessment of a post-emergency pathway with early urological regulation]. / Analyse d'un modèle de circuit court post-urgence avec une régulation précoce urologique.

INTRODUCTION: Urological emergencies represent 7 % of the outpatients at the emergency department (ED). We assessed the effect of setting up a post-emergency consultation (CPU) after deferred urological medical regulation. METHODS: All patients admitted to the ED in a university center over the period December 2017 to July 2018 and for whom a CPU was scheduled were included. The regulation concerned the date of CPU and supplementary exams. The main outcome was the ability to provide an efficient response according to a predefined grid of specific solutions. RESULTS: One hundred and twenty-eight patients were included. The median age was 57 years (18-97). Efficacy of the CPU was 76 %. This rate was lower in no-show patients or consulting for rare and complex motives (47 %, n=60). The no-show were not reachable on the first call in 51.6 % of cases, with a similar age and motives distribution to the others. Only 6,9 % (n=128) of all consultants (n=1863) had been referred to the CPU by emergency physicians. The decision was a second consultation in 70 % (48), a new exam in 10 % (7), deferred emergency surgery in 12 % (8) and finally 18 % (12) of no follow-up. CONCLUSION: CPU following early regulation by a urologist provides an effective response in 76 % of situations. Assessment of "no-shows" helped to identify groups at risk. LEVEL OF EVIDENCE: III.

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients.

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

Antibodies against ARHGDIB are associated with long-term kidney graft loss.

The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP-dissociation inhibitor 2 (ARHGDIB) were significantly associated with graft loss in recipients transplanted with a deceased-donor kidney (N = 3276) but not in recipients of a living-donor kidney (N = 1496). At 10 years after deceased-donor transplantation, recipients with anti-ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death-censored covariate-adjusted graft survival compared to the anti-ARHGDIB-negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32-2.53; P = .0003). These antibodies occur independently from donor-specific anti-HLA antibodies (DSA) or other non-HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non-HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti-ARHGDIB antibodies in all patients awaiting deceased-donor transplantation.

A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival.

BACKGROUND: Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs. METHODS: To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay. RESULTS: Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P = 0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P = 0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11). CONCLUSION: This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients.

BACKGROUND: Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. METHODS: We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. RESULTS: Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P < 0.0001) and CsA/Pred (64%, P < 0.0001). CONCLUSION: These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.

Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure.

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin.

BACKGROUND: Toxicity associated with chemotherapy is a major therapeutic challenge and is caused by chemotherapy-induced DNA damage and inflammation. We have recently reported that cell-free chromatin (cfCh) fragments released from dying cells can readily enter into healthy cells of the body to integrate into their genomes and induce DNA double-strand breaks, apoptosis and inflammation in them. We hypothesized that much of the toxicity of chemotherapy might be due to release of large quantities of cfCh from dying cells that could trigger an exaggerated DNA damage, apoptotic and inflammatory response in healthy cells over and above that caused by the drugs themselves. METHODS: We tested this hypothesis by administering cfCh neutralizing/degrading agents namely, anti-histone antibody complexed nanoparticles, DNase I and a novel DNA degrading agent-Resveratrol-Cu concurrently with five different chemotherapeutic agents to examine if chemotherapy-induced toxicity could be minimized. RESULTS: We observed (i) significant reduction in chemotherapy-induced surge of cfCh in blood; (ii) significant reduction in chemotherapy-induced surge of inflammatory cytokines CRP, IL-6, IFNγ and TNFα in blood; (iii) abolition of chemotherapy-induced tissue DNA damage (γH2AX), apoptosis (active caspase-3) and inflammation (NFκB and IL-6) in multiple organs and peripheral blood mononuclear cells; (iv) prevention of prolonged neutropenia following a single injection of adriamycin and (v) significant reduction in death following a lethal dose of adriamycin. CONCLUSION: Our results suggest that toxicity of chemotherapy is caused to a large extent by cfCh released from dying cells and can be prevented by concurrent treatment with cfCh neutralizing/degrading agents.

Clinical Profile and Treatment Outcome of Drug Resistant Tuberculosis Patients of Western Maharashtra, India.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) imposes formidable burden on national health systems. OBJECTIVES: This study aims to evaluate clinical profile and treatment outcome of drug resistant tuberculosis patients at tertiary care centre using a standardised treatment regimen (STR). METHODS: Retrospective analysis of 146 patients with DR-TB from Solapur district who were treated with STR from period of September 2012 to December 2014 was done. Statistical analysis of treatment outcome data was done to know predictors of treatment success of DR-TB. RESULTS: Out of total 146 bacteriologically proven cases of DR-TB, 95 were males and 51 females. 41% of patients were residents of Solapur city and the rest from different parts of Solapur district. Out of the 146 patients, 130 (89%) patients achieved sputum culture conversion within three months. Treatment outcome of these patients was as followstreatment success in 84 (58%), 20(14%) died, 28(19%) defaulted and failure in 14(9%) patients. Three predictors were identified for successful treatment outcome of DR-TB that include urban residence, patients with chest x-ray findings of moderately advanced disease and patients whose DR-TB status diagnosed by genexpert technology. CONCLUSION: In resource-poor settings, well-designed STR under national programme provides satisfactory results.

Effect of Chlorhexidine Bathing Every Other Day on Prevention of Hospital-Acquired Infections in the Surgical ICU: A Single-Center, Randomized Controlled Trial.

OBJECTIVE: To test the hypothesis that compared with daily soap and water bathing, 2% chlorhexidine gluconate bathing every other day for up to 28 days decreases the risk of hospital-acquired catheter-associated urinary tract infection, ventilator-associated pneumonia, incisional surgical site infection, and primary bloodstream infection in surgical ICU patients. DESIGN: This was a single-center, pragmatic, randomized trial. Patients and clinicians were aware of treatment-group assignment; investigators who determined outcomes were blinded. SETTING: Twenty-four-bed surgical ICU at a quaternary academic medical center. PATIENTS: Adults admitted to the surgical ICU from July 2012 to May 2013 with an anticipated surgical ICU stay for 48 hours or more were included. INTERVENTIONS: Patients were randomized to bathing with 2% chlorhexidine every other day alternating with soap and water every other day (treatment arm) or to bathing with soap and water daily (control arm). MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a composite outcome of catheter-associated urinary tract infection, ventilator-associated pneumonia, incisional surgical site infection, and primary bloodstream infection. Of 350 patients randomized, 24 were excluded due to prior enrollment in this trial and one withdrew consent. Therefore, 325 were analyzed (164 soap and water versus 161 chlorhexidine). Patients acquired 53 infections. Compared with soap and water bathing, chlorhexidine bathing every other day decreased the risk of acquiring infections (hazard ratio = 0.555; 95% CI, 0.309-0.997; p = 0.049). For patients bathed with soap and water versus chlorhexidine, counts of incident hospital-acquired infections were 14 versus 7 for catheter-associated urinary tract infection, 13 versus 8 for ventilator-associated pneumonia, 6 versus 3 for incisional surgical site infections, and 2 versus 0 for primary bloodstream infection; the effect was consistent across all infections. The absolute risk reduction for acquiring a hospital-acquired infection was 9.0% (95% CI, 1.5-16.4%; p = 0.019). Incidences of adverse skin occurrences were similar (18.9% soap and water vs 18.6% chlorhexidine; p = 0.95). CONCLUSIONS: Compared with soap and water, chlorhexidine bathing every other day decreased the risk of acquiring infections by 44.5% in surgical ICU patients.

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands.

INTRODUCTION: Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres. METHODS: Cross-sectional and longitudinal national data from living KTRs ≤30 years of age (≥1-year post-transplant, eGFR >20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (≥18-30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres. RESULTS: Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment. CONCLUSION: Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT.