Clearance Of Fragments Research Articles

Factors predicting stone-free rates after retrograde intrarenal surgery for lower pole kidney stones A single-center, retrospective analysis.

We aimed to investigate the factors impacting stone clearance following retrograde intrarenal surgery (RIRS) for lower pole kidney stones and to determine whether there is a significant relationship between the infundibular pelvic angle (IPA) of the kidney's lower pole and stone fragment clearance. We retrospectively reviewed patients who underwent flexible ureteroscopy (f-URS) for lower pole renal calculi between December 2020 and July 2023 at our institution. Patient demographics and stone parameters were recorded, including stone size, number, volume, density, and IPA. Intraoperative data, including total operative time, lasing time, type of laser used, and stone composition, were collected and analyzed. All patients underwent a computed tomography (CT) scan at three months followup. We recorded the presence of residual stones and the percentage of stone volume reduction. Patients with a stone size ≤3 mm were deemed stone-free. All patients were discharged home on the same operative day. A total of 123 patients were included in the study: 71 in the stone-free group (group 1) and 52 in the residual stones group (group 2). On univariate analysis, there were significant differences between the two groups in terms of stone size, IPA, and the type of ureteroscopy used. At three-month followup, 96% (24/25) of patients with an IPA <30° had residual stones compared to 28.6% (28/98) of patients with an IPA >30° (p<0.001). There was no significant difference in the intraoperative or postoperative complications between the two groups. On multivariate analysis, IPA and stone size were the only predictive factors for the presence of residual stones. Twelve patients (23.1%) from group 2 required retreatment. RIRS is an effective treatment option for the management of lower pole kidney stones. IPA, in conjunction with stone size, appears to dictate the stone clearance rates of RIRS for lower pole stones.

Vitamin D supply, respiratory viral infections and persistent wheezing in children: how significant is the relationship?

The review discusses the multifaceted effect of vitamin D on antiviral immunity, induction of antimicrobial peptides, functional activity of immunocompetent cells, autophagy processes, clearance of viruses and viral fragments. The relationship between vitamin D and allergic inflammatory cells, its modulating and tolerogenic potential is considered. The inhibitory effect of vitamin D on eosinophils, mast cells, the production of pro-inflammatory and proallergic mediators, and the synthesis of IgE has been shown. The protective role of vitamin D in the development of remodeling and hyperresponsiveness of the respiratory tract has been established by reducing the number of goblet cells, mucus hypersecretion, and the expression of metalloproteinases. The effects of vitamin D on the replication of respiratory viruses and experimental resistance to them through the induction of antimicrobial peptides and other mechanisms have been demonstrated. Data from clinical studies on the preventive effect of vitamin D on the incidence of respiratory infections and episodes of persistent wheezing in children are presented. Children with respiratory syncytial infection and vitamin D deficiency were more likely to require respiratory support and mechanical ventilation. The preventive role of vitamin D in the development of obstructive bronchitis in children and severe bronchiolitis in infants has been shown. It has been established that normal levels of 25(OH)D in the mother significantly reduce the risk of developing bronchial obstruction in the child. Alternative data that do not support a protective effect of vitamin D on respiratory morbidity and wheezing in children are discussed. Further monitoring studies that take into account geographic location and analysis of the dose of cholecalciferol used to assess its preventive role in the development of wheezing and bronchial asthma in children are advisable.

A minimal physiologically based pharmacokinetic model to study the combined effect of antibody size, charge, and binding affinity to FcRn/antigen on antibody pharmacokinetics.

Protein therapeutics have revolutionized the treatment of a wide range of diseases. While they have distinct physicochemical characteristics that influence their absorption, distribution, metabolism, and excretion (ADME) properties, the relationship between the physicochemical properties and PK is still largely unknown. In this work we present a minimal physiologically-based pharmacokinetic (mPBPK) model that incorporates a multivariate quantitative relation between a therapeutic's physicochemical parameters and its corresponding ADME properties. The model's compound-specific input includes molecular weight, molecular size (Stoke's radius), molecular charge, binding affinity to FcRn, and specific antigen affinity. Through derived and fitted empirical relationships, the model demonstrates the effect of these compound-specific properties on antibody disposition in both plasma and peripheral tissues using observed PK data in mice and humans. The mPBPK model applies the two-pore hypothesis to predict size-based clearance and exposure of full-length antibodies (150kDa) and antibody fragments (50-100kDa) within a onefold error. We quantitatively relate antibody charge and PK parameters like uptake rate, non-specific binding affinity, and volume of distribution to capture the relatively faster clearance of positively charged mAb as compared to negatively charged mAb. The model predicts the terminal plasma clearance of slightly positively and negatively charged antibody in humans within a onefold error. The mPBPK model presented in this work can be used to predict the target-mediated disposition of a drug when compound-specific and target-specific properties are known. To our knowledge, a combined effect of antibody weight, size, charge, FcRn, and antigen has not been incorporated and studied in a single mPBPK model previously. By conclusively incorporating and relating a multitude of protein's physicochemical properties to observed PK, our mPBPK model aims to contribute as a platform approach in the early stages of drug development where many of these properties can be optimized to improve a molecule's PK and ultimately its efficacy.

Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis.

Endometriosis (EMs) is a prevalent gynecological disorder characterized by the growth of uterine tissue outside the uterine cavity, causing debilitating symptoms and infertility. Despite its prevalence, the exact mechanisms behind EMs development remain incompletely understood. This article presents a comprehensive overview of the relationship between gut microbiota imbalance and EMs pathogenesis. Recent research indicates that gut microbiota plays a pivotal role in various aspects of EMs, including immune regulation, generation of inflammatory factors, angiopoietin release, hormonal regulation, and endotoxin production. Dysbiosis of gut microbiota can disrupt immune responses, leading to inflammation and impaired immune clearance of endometrial fragments, resulting in the development of endometriotic lesions. The dysregulated microbiota can contribute to the release of lipopolysaccharide (LPS), triggering chronic inflammation and promoting ectopic endometrial adhesion, invasion, and angiogenesis. Furthermore, gut microbiota involvement in estrogen metabolism affects estrogen levels, which are directly related to EMs development. The review also highlights the potential of gut microbiota as a diagnostic tool and therapeutic target for EMs. Interventions such as fecal microbiota transplantation (FMT) and the use of gut microbiota preparations have demonstrated promising effects in reducing EMs symptoms. Despite the progress made, further research is needed to unravel the intricate interactions between gut microbiota and EMs, paving the way for more effective prevention and treatment strategies for this challenging condition.

Increased formation of neutrophil extracellular traps induced by autophagy and identification of autophagy-related biomarkers in systemic lupus erythematosus.

Abnormal death of neutrophils and the subsequent ineffective clearance of cell fragments result in production of autoantigens that can lead to systemic lupus erythematosus (SLE). Excessive formation of neutrophil extracellular traps (NETs) can trigger the synthesis of pro-inflammatory cytokines such as type I interferons, leading to tissue damage and immune dysfunction in SLE patients. In this study, we found that a decrease in neutrophil counts in the peripheral blood was correlated with clinical parameters in SLE patients. Patients with low neutrophil counts had high renal activity index and chronicity index scores. NET formation and neutrophil autophagy in SLE patients were increased. The autophagy inhibitor hydroxychloroquine was shown to restrict NET formation. Using comprehensive bioinformatics analysis, we found that the expression of the autophagy-related gene, hypoxia-inducible factor 1A (HIF1A), was enhanced in peripheral neutrophils and in the renal glomeruli in SLE patients. Targeting HIF1A could be a potential therapeutic approach for SLE.

Office-based kidney stone management with new ultrasound technologies

Despite the growing incidence of urinary stones, the fundamental interventions for urinary stones have remained the same for several decades. However, technical innovations in ultrasound have enabled new strategies for stone management. Our team aims to employ these methods to establish a new paradigm to treat stones in an office or clinic rather than a surgical suite. Technologies include new imaging methods to detect and characterize stones, burst wave lithotripsy to fragment stones using focused ultrasound rather than shock waves, and ultrasonic propulsion to promote clearance of fragments, all using a single ultrasound platform. This presentation will describe the principles and development of these technologies, as well as the fruitful partnerships between teams of basic scientists, engineers, physicians, and industry that have enabled rapid development of these concepts to successful clinical trials. [Work supported by NIDDK P01 DK043881 and the Focused Ultrasound Foundation.]

Family with sequence similarity 134 member B-mediated reticulophagy ameliorates hepatocyte apoptosis induced by dithiothreitol.

BACKGROUNDEndoplasmic reticulum (ER) stress-related hepatocyte apoptosis is responsible for multiple hepatic diseases. Previous studies have revealed that endoplasmic reticulophagy (ER-phagy) promotes the selective clearance of damaged ER fragments during ER stress, playing a crucial role in maintaining ER homeostasis and inhibiting apoptosis. Family with sequence similarity 134 member B (FAM134B) is a receptor involved in ER-phagy that can form a complex with calnexin (CNX) and microtubule-associated protein 1 light chain 3 (LC3). The complex can mediate the selective isolation of ER fragments to attenuate hepatocyte apoptosis. However, the precise regulatory mechanisms remain unclear.AIMTo elucidate the effect of FAM134B-mediated ER-phagy on ER stress-induced apoptosis in buffalo rat liver 3A (BRL-3A) rat hepatocytes and the potential regulatory mechanisms.METHODSER stress-related hepatocyte apoptosis was induced using dithiothreitol (DTT). Proteins related to ER stress and autophagy were measured with western blotting. Protein complex interactions with FAM134B were isolated by co-immunoprecipitation. ER-phagy was evaluated in immunofluorescence experiments. Cell cycle distribution and apoptosis were measured by flow cytometry. Mitochondrial Ca2+ levels were evaluated by the co-localization of intracellular Ca2+-tracker and Mito-tracker. The small interfering RNA against FAM134B was used to knockdown FAM134B in BRL-3A cells.RESULTSER stress-related and autophagy-related proteins in BRL-3A cells were elevated by both short and long-term DTT treatment. Furthermore, co-immunoprecipitation confirmed an interaction between FAM134B, CNX, FAM134B, and LC3 in BRL-3A cells. Immunofluorescence assays revealed that autolysosomes significantly decreased following short-term DTT treatment, but increased after long-term treatment. Mitochondrial Ca2+ levels and apoptotic rates were dramatically elevated, and more cells were arrested in the G1 stage after short-term DTT treatment; however, these decreased 48 h later. Moreover, FAM134B downregulation accelerated mitochondrial apoptotic pathway activation and aggravated hepatocyte apoptosis under ER stress.CONCLUSIONFAM134B-mediated ER-phagy attenuates hepatocyte apoptosis by suppressing the mitochondrial apoptotic pathway. Our findings provide new evidence highlighting the importance of FAM134B-mediated ER-phagy in attenuating hepatocyte apoptosis.

Association of plasma tumor tissue modified viral HPV DNA (TTMV) with tumor burden, treatment type, and outcome: A translational analysis from NRG-HN002.

6006 Background: NRG-HN002 was a phase II trial that randomized patients with p16-positive oropharynx cancer to 60 Gy IMRT with concurrent cisplatin (IMRT-C) or 60 Gy accelerated IMRT. The protocol specified plasma collection at pretreatment (t0), intratreatment (20-28 Gy, t1), and 2 weeks to 1 month posttreatment (t2); at these timepoints, TTMV was assayed. A prespecified analysis evaluated: association of t0 TTMV to gross tumor volume (GTV) of primary and lymph nodes; t0-t1 decrease in TTMV; and association of t2 TTMV to treatment and outcome. Methods: TTMV was quantified as fragments/mL of plasma. If TTMV-HPV16 was not detected (&lt;5 fragments/mL) or was a low value, the specimen was tested for TTMV-HPV18, -HPV31, -HPV33, and -HPV35. The distribution of t0 TTMV fragments was highly skewed, so these data were log-transformed; their correlation to GTV was measured by Pearson coefficient. Paired and two-sample t-tests were used to compare t0 and t1 log-transformed fragments within and between arms. Proportions of TTMV detection at t2 between arms were compared using Fisher’s exact test. Rates of undetectability and fragment clearance (≥94% reduction from t0) at t2 were estimated. The negative predictive value (NPV) was estimated for 2-year locoregional failure (LRF) and progression-free survival (PFS). Results: Of 306 eligible patients, 164 (53.6%) donated at least one specimen. The median collection time/RT dose was -2.6 days before RT (Q1-Q3, -4.0-0.0), at 24 Gy (22-28), and 25.5 days after RT end (18-31). The t0, t1, and t2 patient participation rates were 53.6%, 45.4%, and 42.5%. Zero TTMV fragments were detected in 10.4% at t0, 19.4% at t1, and 93.1% at t2. At t0, t1, and t2, 83.5%, 79.1%, and 6.2% had detectable TTMV; 78.0%, 73.4%, and 5.4% had TTMV-HPV16. In correlating GTV to t0 TTMV fragments, the Pearson coefficient was 0.30 (95% CI 0.15-0.44). In a linear model, T stage (p=0.01) and N stage (p=0.004) were positively associated with t0 TTMV fragments. On the IMRT-C arm, the t0-to-t1 mean change was -1.06 (p=0.0009), and for IMRT, it was -0.22 (p=0.35) (p=0.03 between arms). The t2 TTMV detectability rate was 3.3% for IMRT-C vs 8.7% for IMRT (p=0.28). The t2 TTMV undetectability rate was 93.8% and the fragment clearance rate was 95.4%. Two-year LRF and PFS were 6.2% and 91.4%. The NPV of t2 undetectability was 95.0% (95% CI 89.4-98.1) for 2-year LRF and 93.3% (95% CI 87.3-97.1) for 2-year PFS, and for fragment clearance was 94.3% and 92.7%. Conclusions: Feasibility of the TTMV-HPV assay in clinical trial specimens was established. About 10% of p16-positive patients had zero TTMV fragments at baseline. Among those with TTMV detectability, 6.6% had types other than TTMV-HPV16. T and N stage were positively associated with TTMV fragments. The IMRT-C arm achieved rapid TTMV undetectability unlike IMRT. The NPV of posttreatment undetectability was 93-95% for 2-year LRF and PFS.

The evaluation of morphology of renal pelvicalyceal system's and infundibulopelvic anatomy of kidney's lower pole in post-mortem series.

Urinary system stones are frequently encountered in the community. Together with technological developments, introduction of new treatment procedures such as extracorporeal shock wave lithotripsy, percutaneous nephrolithotomy and retrograde intrarenal surgery has further reduced morbidity, mortality and hospitalisation time of patients. In order to maximise success and to reduce complications of these procedures, it is necessary to evaluate anatomy and morphological differences of kidney collector system before the procedure. This study was conducted for the purpose of determining the morphology of the kidney collector system and the negative anatomic factors of the lower pole in autopsy cases performed in our institution. Eighty two kidney units obtained from 41 autopsy cases conducted in Faculty of Medicine Department of Forensic Medicine, Sivas Cumhuriyet University between September 2017 and September 2018 were included in the study. Percentages were found as 78% for intrarenal pelvis, 13.4% for borderline pelvis, 6.1% for extrarenal pelvis and 2.4% for pelvic nonexistence. When pelvicalyceal anatomy was evaluated, percentages were found as 32.9% for bicalyceal, 26.8% for tricalyceal, 20.7% for multicalyceal, and 19.5% for unclassified calyceality. When it was evaluated according to opening of calyces into the renal pelvis based on Sampaio classification, percentages were found as 30.5% for AI, 17.1% for type II, 28% for BI, 18.3% for BII, and 6.1% for unevaluated part. Infundibular lengths of kidney's lower pole were detected as under 3 cm in 39% and over 3 cm in 61% of all cases. Infundibulopelvic angles of kidney's lower pole were measured as under 70o in 42.7% and over 70o in 57.3% of all cases. In our study, there was no statistically significant difference between the right and left kidneys in terms of collecting system morphology and lower pole's negative anatomical factors. Only infundibular length which is one of the collecting system morphology and lower pole's negative anatomical factors were statistically shorter in females than males. There was no difference in terms of other parameters. In conclusion, the findings of this study are largely consistent with the results of similar studies. This reveals that renal collecting system morphology and negative anatomic factors in the lower pole collecting system in human are roughly similar. In clinical practice, pre-treatment computed tomography and, if necessary, magnetic resonance urography evaluation of the lower pole negative anatomic factors may contribute to gain preliminary information about both the clearance of stone fragments especially after shock wave lithotripsy and retrograde intrarenal surgery procedures and perioperative complications proactively.

Theranostic F-SLOH mitigates Alzheimer's disease pathology involving TFEB and ameliorates cognitive functions in Alzheimer's disease models

Accumulation of amyloid-β (Aβ) oligomers and phosphorylated Tau aggregates are crucial pathological events or factors that cause progressive neuronal loss, and cognitive impairments in Alzheimer's disease (AD). Current medications for AD have failed to halt, much less reverse this neurodegenerative disorder; therefore, there is an urgent need for the development of effective and safe drugs for AD therapy. In the present study, the in vivo therapeutic efficacy of an Aβ-oligomer-targeted fluorescent probe, F-SLOH, was extensively investigated in 5XFAD and 3XTg-AD mouse models. We have shown that F-SLOH exhibits an efficient inhibitory activity against Aβ aggregation in vivo, and acts as an effective theranostic agent for the treatment of multiple neuropathological changes in AD mouse models. F-SLOH has been found to significantly reduce not only the levels of Aβ oligomers, Tau aggregates and plaques but also the levels of amyloid precursor protein (APP) and its metabolites via autophagy lysosomal degradation pathway (ALP) in the brains of 5XFAD and 3XTg-AD mice. It also reduces astrocyte activation and microgliosis ultimately alleviating neuro-inflammation. Furthermore, F-SLOH mitigates hyperphosphorylated Tau aggregates, synaptic deficits and ameliorates synaptic memory function, and cognitive impairment in AD mouse models. The mechanistic studies have shown that F-SLOH promotes the clearance of C-terminal fragment 15 (CTF15) of APP and Paired helical filaments of Tau (PHF1) in stable cell models via the activation of transcription factor EB (TFEB). Moreover, F-SLOH promotes ALP and lysosomal biogenesis for the clearance of soluble, insoluble Aβ, and phospho Tau. Our results unambiguously reveal effective etiological capabilities of theranostic F-SLOH to target and intervene multiple neuropathological changes in AD mouse models. Therefore, F-SLOH demonstrates tremendous therapeutic potential for treating AD in its early stage.

Contribution of Impaired DNASE1L3 Activity to Anti-DNA Autoantibody Production in Systemic Lupus Erythematosus.

Anti-DNA autoantibodies are pathogenic in systemic lupus erythematosus (SLE). Cell-free chromatin associated long DNA fragments are antigens for anti-DNA antibodies. In health state, released by cell death and actively secreted by live cells, these cell-free DNA are cleared by deoxyribonucleases (DNASES). In SLE, cell-free DNA are accumulated. The defective clearance of long fragments of cell-free DNA in SLE is largely attributed to impaired deoxyribonuclease 1 like 3 (DNASE1L3). DNASE1L3 null mutation results in monogenic SLE. The SLE risk single-nucleotide polymorphism (rs35677470) encodes R260C variant DNASE1L3, which is defective in secretion, leading to reduced levels of DNASE1L3. In addition, neutralizing autoantibodies to DNASE1L3 are produced in SLE to inhibit its enzymatic activity.

Which Factors Affect the Spontaneous Stone Passage After Flexible Ureteroscopic Lithotripsy for Renal Stones?

Objectives: The aim of this study was to investigate factors predicting spontaneous stone passage after Flexible Ureteroscopic Lithotripsy (fURS) for renal stones. Materials and Methods: This study included 239 patients with renal stones who underwent fURS using the dusting technique. The final outcome was evaluated 3 months postoperatively and the Residual Fragment status (RFs) was defined as any residual stone fragments greater than 2 mm. Univariate and multivariate analyses of possible predictive factors associated with spontaneous clearance of residual renal fragments were performed. Results:186 patients (77.8%) had achieved an Stone-Free status (SFs) and 53 patients (22.2%) were considered with RFs. Univariate analysis showed the stone location, stone number, stone size, stone CT value, IPA degree, the presence of hydronephrosis and stone covered with purulent substance were all associated with RFs (P&lt;0.05). Multivariate logistic regression analysis showed that larger stone size (P=0.001), multiple stones (P=0.038), the IPA of &lt;45° (P=0.035), the presence of hydronephrosis (P=0.045), the stone CT value ≥ 1000 (P=0.047) were all significantly associated with higher rates of residual stone after fURS. The stone covered with purulent substance was found to be the strongest predictor of RFs (P=0.027). However, the presence of lower pole stone had no significant influence on stone clearance after fURS (P=0.263). Conclusions: Stone number, stone size , an IPA of &lt;45°, stone CT value ≥ 1000 HU, stone covered with purulent substance and presence of hydronephrosis are all predictive factors of the spontaneous clearance of residual renal fragments after fURS.

Randomized control trial of ultrasonic propulsion to facilitate clearance of residual kidney stone fragments

The goal is to test effectiveness and safety of transcutaneous ultrasound pulses for facilitating clearance of residual urinary stone fragments in a randomized control trial (RCT). The study is conducted in a clinic setting with the control and treatment arms undergoing all the same activities with the exception of the ultrasonic propulsion procedure and associated pain questionnaire. Subjects are followed 90 days for assessment of adverse events and for up to 5 years for stone growth and symptomatic stone visits. Twenty-six of 33 subjects have been recruited in each arm The most recent treatment is reported. The subject received shock wave lithotripsy and did not pass any fragments for 17 months. The subject was randomized to the treatment arm. Fragments began moving with the third 3-s propulsion pulse at output 2 of 5 levels. Fifty-two percent of propulsion pulses (41 of 79) resulted in fragment movement. The subject reported no pain at the beginning or end of the procedure and telephoned within 2 h to report passing 9 fragments, no hematuria, and no adverse events. The treatment results of this RCT are compelling as an immediate and casual effect was measured. [Work supported by NIH-P01-DK043881 and VA Puget Sound resources.]

Chimpanzees (Pan troglodytes) adapt their nesting behavior after large-scale forest clearance and community decline.

Chimpanzees (Pan troglodytes) build nests at night for sleeping and occasionally during daytime for resting. Over the course of seven years, forest fragments in Bulindi, Uganda, were reduced in size by about 80% when landowners converted forest to agricultural land. However, unlike other studies on nesting behavior in response to habitat disturbance, chimpanzees at Bulindi had no opportunity to retreat into nearby undisturbed forest. To understand behavioral adaptations to forest clearance, we compared Bulindi chimpanzees' nesting characteristics before and after this period of major deforestation. After deforestation, chimpanzees built nests at lower heights in shorter trees, and reused a larger proportion of their nests. Additionally, average nest group size increased after deforestation, even though community size declined by approximately 20% over the same period. The substantial decrease in available forest habitat may have caused the chimpanzees to aggregate for nesting. However, more cohesive nesting may also have been influenced by dietary shifts (increased reliance on agricultural crops) and a need for enhanced safety with increased human encroachment. Conversely, the chimpanzees selected similar tree species for nesting after deforestation, apparently reflecting a strong preference for particular species, nested less often in exotic species, and built integrated nests (constructed using multiple trees) at a similar frequency as before fragment clearance. Chimpanzees living in unprotected habitat in Uganda, as at Bulindi, face mounting anthropogenic pressures that threaten their survival. Nevertheless, our study shows that chimpanzees can adjust their nesting behavior flexibly in response to rapid, extensive habitat change. While behavioral flexibility may enable them to cope with deforestation, at least to a certain point, the long-term survival of chimpanzees in fast-changing human-modified landscapes requires intensive conservation efforts.

Acquired decrease of the C3b/C4b receptor (CR1, CD35) and increased C4d deposits on erythrocytes from ICU COVID-19 patients

In order to study the mechanisms of COVID-19 damage following the complement activation phase occurring during the innate immune response to SARS-CoV-2, CR1 (the regulating complement activation factor, CD35, the C3b/C4b receptor), C4d deposits on Erythrocytes (E), and the products of complement activation C3b/C3bi, were assessed in 52 COVID-19 patients undergoing O2 therapy or assisted ventilation in ICU units in Rheims France. An acquired decrease of CR1 density on E from COVID-19 patients was observed (Mean = 418, SD = 162, N = 52) versus healthy individuals (Mean = 592, SD = 287, N = 400), Student’s t-test p < 10−6, particularly among fatal cases, and in parallel with several parameters of clinical severity. Large deposits of C4d on E in patients were well above values observed in normal individuals, mostly without concomitant C3 deposits, in more than 80% of the patients. This finding is reminiscent of the increased C4d deposits on E previously observed to correlate with sub endothelial pericapillary deposits in organ transplant rejection, and with clinical SLE flares. Conversely, significant C3 deposits on E were only observed among ¼ of the patients. The decrease of CR1/E density, deposits of C4 fragments on E and previously reported detection of virus spikes or C3 on E among COVID-19 patients, suggest that the handling and clearance of immune complex or complement fragment coated cell debris may play an important role in the pathophysiology of SARS-CoV-2. Measurement of C4d deposits on E might represent a surrogate marker for assessing inflammation and complement activation occurring in organ capillaries and CR1/E decrease might represent a cumulative index of complement activation in COVID-19 patients.Taken together, these original findings highlight the participation of complement regulatory proteins and indicate that E are important in immune pathophysiology of COVID-19 patients. Besides a potential role for monitoring the course of disease, these observations suggest that novel therapies such as the use of CR1, or CR1-like molecules, in order to down regulate complement activation and inflammation, should be considered.

Effect of tamsulosin versus tamsulosin plus tadalafil on renal calculus clearance after shock wave lithotripsy: An open-labelled, randomised, prospective study

ObjectivesTo compare the efficacy of tamsulosin versus tamsulosin plus tadalafil in achieving clearance of fragments after shock wave lithotripsy (SWL) to treat renal calculi. MethodsBetween January 2016 to December 2017, 140 patients with solitary, non-branched, non-lower calyceal renal calculus and measuring less than 20 mm and treated with SWL were randomized to tamsulosin (group A) or tamsulosin plus tadalafil (group B). Therapy was given for a period of 4 weeks. Stone clearance rate, analgesic requirement, occurrence of steinstrasse, need for auxiliary procedures (endoscopic treatment), and adverse effects of drugs were recorded. ResultsThe overall clearance rate was 72.5% (50/69) in the group A and 90.1% (64/71) in the group B (p=0.007). For stones up to 12 mm, the difference in the clearance rate was significant (p=0.039) while it was not so for stones larger than 12 mm (p=0.151). There was no statistically significant difference between the two groups with regards to analgesic requirement (p=0.94), occurrence of steinstrasse (p=0.101), need for auxiliary procedures (p=0.76), and adverse effects of the drugs (p=0.148). ConclusionOur study shows that adjunctive medical expulsive therapy with tamsulosin and tadalafil achieves better clearance rate than tadalafil alone in patients receiving SWL for renal stones.

Adjunctive medical expulsive therapy with tamsulosin for repeated extracorporeal shock wave lithotripsy: a systematic review and meta-analysis.

ABSTRACTPurpose:To evaluate the efficacy of adjunctive medical expulsive therapy (MET) with tamsulosin for the promotion of stone fragments clearance for repeated extracorporeal shock wave lithotripsy (ESWL).Materials and Methods:This meta-analysis was conducted by systematic search for randomized controlled trial (RCT) studies in PubMed/Medline, Scopus, Cochrane Library, Web of Science databases in January 2020, which compared tamsulosin with either placebo or non-placebo control for repeated ESWL. The primary endpoint was stone-free rate (SFR), the second endpoints were stone clearance time and complications. The quality assessment of included studies was performed by using the Cochrane System and Jadad score.Results:7 RCTs were included in this meta-analysis. Tamsulosin provided higher SFR (for stones larger than 1cm, OR: 5.56, p=0.0003), except for patients with stones less than 1cm. For patients with renal stones (OR: 2.97, p=0.0005) or upper ureteral stones (OR: 3.10, p=0.004), tamsulosin can also provide a higher SFR. In addition, tamsulosin provided a shorter stone clearance time (WMD: −9.40, p=0.03) and lower pain intensity (WMD=-17.01, p <0.0001) and incidences of steinstrasse (OR: 0.37, p=0.0002).Conclusion:Adjunctive MET with tamsulosin is effective in patients with specific stone size or location that received repeated ESWL. However, no well-designed RCT that used computed tomography for the detection and assessment of residual stone fragments was found. More studies with high quality and the comparison between tamsulosin and secondary ESWL are needed in the future.

Alpha-blockers after shock wave lithotripsy for renal or ureteral stones in adults.

Shock wave lithotripsy (SWL) is a widely used method to treat renal and ureteral stone. It fragments stones into smaller pieces that are then able to pass spontaneously down the ureter and into the bladder. Alpha-blockers may assist in promoting the passage of stone fragments, but their effectiveness remainsuncertain. OBJECTIVES: To assess the effects of alpha-blockers as adjuvant medical expulsive therapy plus usual care compared to placebo and usual care or usual care alonein adults undergoing shock wave lithotripsy for renal or ureteral stones. We performed a comprehensive literature search of the Cochrane Library, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, several clinical trial registries and grey literature for published and unpublished studies irrespective of language. The date of the most recent search was 27 February 2020. We included randomized controlled trials of adults undergoing SWL. Participants in the intervention group had to have received an alpha-blocker as adjuvant medical expulsive therapy plus usual care. For the comparator group, we considered studies in which participants received placebo. Two review authors independently selected studies for inclusion/exclusion, and performed data abstraction and risk of bias assessment. We conducted meta-analysis for the identified dichotomous and continuous outcomes using RevManWeb according to Cochrane methods using a random-effects model. We judged the certainty of evidence on a per outcome basis using GRADE. We included 40 studies with 4793 participants randomized to usualcare and an alpha-blocker versus usual care alone. Only four studies were placebo controlled. The mean age of participants was 28.6 to 56.8years and the mean stone size prior to SWL was 7.1 mm to 13.2mm. The most widely usedalpha-blocker was tamsulosin; others weresilodosin, doxazosin, terazosin and alfuzosin. Alpha-blockers may improve clearance of stone fragments after SWL (risk ratio (RR) 1.16, 95% confidence interval (CI) 1.09 to 1.23; I² = 78%; studies = 36; participants = 4084; low certainty evidence). Based on the stone clearance rate of 69.3% observed in the control arm, an alpha-blocker may increase stone clearance to 80.4%. This corresponds to 111 more (62 more to 159 more) participants per 1000 clearing their stone fragments. Alpha-blockers may reduce the need for auxiliary treatments after SWL (RR 0.67, 95% CI 0.45to 1.00; I² = 16%; studies = 12; participants = 1251; low certainty evidence), but also includes the possibility of no effect. Based on a rate of auxiliary treatments in the usual care arm of 9.7%, alpha-blockers may reduce the rate to 6.5%. This corresponds 32fewer (53 fewer to 0fewer) participants per 1000 undergoing auxiliary treatments. Alpha-blockers may reduce major adverse events (RR 0.60, 95% CI 0.46 to 0.80; I² = 0%; studies = 7; participants = 747; low certainty evidence). Major adverse events occurred in 25.8% of participants in the usual care group; alpha-blockers would reduce this to 15.5%. This corresponds to 103 fewer (139 fewer to 52 fewer) major adverse events per 1000 with alpha-blocker treatment. None of the reported major adverse events appeared drug-related; most were emergency room visits or rehospitalizations. Alpha-blockers may reduce stone clearance timein days (mean difference (MD) -3.74, 95% CI -5.25 to -2.23; I² = 86%; studies = 14; participants = 1790; low certainty evidence). We found no evidence for the outcome of quality of life. For those outcomes for which we were able to perform subgroup analyses, we found no evidence of interaction with stone location, stone size or type of alpha-blocker. We were unable to conduct an analysis by lithotripter type. The results were also largely unchanged when the analyses were limited to placebo controlled studies and those in which participants explicitly only received a single SWL session. Based on low certainty evidence, adjuvant alpha-blocker therapy following SWL in addition to usual care may resultin improved stone clearance, less need for auxiliary treatments, fewermajor adverse events and a reducedstone clearance time compared to usual care alone. We did not find evidence for quality of life. The low certainty of evidence means that our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

Comparative Study Between Holmium: Yag Laser and Pneumatic Lithotripsy in the Management of Upper Ureteric Stone

Background:Among various intracorporeal lithotripters, Pneumatic lithotriptorhas become the widely used tool for the treatment of ureteric stones. Recently the Holmium:YAG laser has been used with a wide range of potential urological applications, including intracorporeal lithotripsy of ureteric stones. Objective: To compare the treatment of upper ureteric stone between laser and pneumatic lithotripsy. Materials and methods: One hundred patients with upper ureteric stone who underwent ureteroscopic lithotripsy in the Department of Urology, CMH, Dhakafrom October 2012 to September 2015 were enrolled in this study. Patients were divided into two groups. Group A (LL) were treated with holmium: YAG laser and Group B (PL) were treated with pneumatic lithotripsy. Two procedures were compared in term of stone fragmentation, stone clearance rate, duration of lithotripsy, complications and duration of post operativehospital stay. Patients were monitored as outpatients after one month and after three months with a kidney ureter and bladder radiograph and ultrasonograph. Patients with migrated fragments or incomplete clearance underwent an auxiliary procedure such as Extra Corporeal shock wave lithotripsy (ESWL). Results: Mean stone size was 1.36 ± 0.36 cm in group A (LL) and 1.37± 0.36 cm in group B (PL). The immediate stone clearance rate was significantly higher inGroup A (94.0%) than Group B (76.0%). Fragments proximal migration were 6.0% in LL group and 24.0% in PL group. Use of stone retrieval equipments (baskets, forceps) was 16.0% and 64.0% in LL and PL group respectively (p&lt;0.05) and stone fragments clearance requiring auxiliary procedures were 6% and 24% (p&lt;0.05) in LL and PL group respectively. The mean lithotripsy time 40.46 ± 19.25 min and 36.86 ± 14.83 min and mean period of post operative hospital stay was 2.32 ± 1.22 days and 2.44 ± 1.18 days in the LL and PL group respectively. Periprocedural complications like hemorrhage, mucosal disruption/ perforation were almost same in both groups. Conclusion: In this study stone clearance and fragmentation of stone in Holmium:YAG assisted ureteroscopy was significantly higher than pneumatic lithotripsy group. The need for auxiliary procedure like ESWL for proximally migrated fragments was significantly less inHolmium:YAG assisted ureterocopy compared with pneumatic lithotripsy. Bangladesh Journal of Urology, Vol. 22, No. 2, July 2019 p.160-165

Hfq and RNase R Mediate rRNA Processing and Degradation in a Novel RNA Quality Control Process.

RNA quality control pathways are critical for cell survival. Here, we describe a new surveillance process involved in the degradation of highly structured and stable ribosomal RNAs. The results demonstrated that the RNA chaperone Hfq and the 3'-5' exoribonuclease R mediate the elimination of detrimental rRNA fragments and are required for the correct processing of rRNA precursors. Escherichia coli cells lacking both Hfq and RNase R accumulate a high level of 16S- and 23S-derived rRNA fragments. Hfq and RNase R were also shown to participate in the maturation of 16S and 23S rRNA precursors. This correlates with the fact that in the absence of Hfq and RNase R, there are severe ribosome assembly defects and a sharp reduction in 70S ribosome levels. Hfq and RNase R may act independently or in a complex, as protein interaction studies revealed that these RNA-binding proteins can associate. This is the first demonstration that the well-conserved Hfq and RNase R proteins act on common regulatory pathways, unraveling previously unknown mechanisms of rRNA surveillance with important consequences for translation and cell survival.IMPORTANCE Quality control pathways that oversee the quality of stable RNA molecules are critical for the cell. In this work, we demonstrate, for the first time, a functional link between Hfq and RNase R in the processing and degradation of the highly structured rRNAs. These RNA-binding proteins are required for the maturation of 16S and 23S rRNAs and correct ribosome assembly. Furthermore, they participate in the degradation of rRNAs and clearance of toxic rRNA fragments from the cell. Our studies have also shown that Hfq and RNase R can form a complex. In summary, the cooperation between Hfq and RNase R in metabolic pathways of stable RNAs may represent a broader mechanism of RNA quality control, given the high conservation of these RNA-binding proteins throughout evolution.