Tubular Lesions Research Articles

Clr-f expression regulates kidney immune and metabolic homeostasis

The C-type lectin-related protein, Clr-f, encoded by Clec2h in the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse (Clr-f−/−) by targeted deletions in the Clec2h gene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis of Clr-f−/− mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies of Clr-f−/− mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in a Rag1−/−Clr-f−/− background reveals that Clr-f−/− mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis.

Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway.

In this investigation, a potentially novel signaling pathway in gentamicin-induced acute kidney injury—worsened by overexpression of proximal tubular enzyme, myo-inositol oxygenase (MIOX)—was elucidated. WT, MIOX-transgenic (MIOX-Tg), and MIOX-KO mice were used. Gentamicin was administered to induce tubular injury. MIOX-Tg mice had severe tubular lesions associated with increased serum creatinine and proteinuria. Lesions were relatively mild, with no rise in serum creatinine and no albuminuria in MIOX-KO mice. Transfection of HK-2 cells with MIOX-pcDNA led to increased gentamicin-induced reactive oxygen species (ROS). Marked increase of ROS-mediated lipid hydroperoxidation was noted in MIOX-Tg mice, as assessed by 4-HNE staining. This was associated with increased expression of arachidonate 12-lipoxygenase (ALOX-12) and generation of 12-hydroxyeicosatetraenoic acid (12-HETE). In addition, notable monocyte/macrophage influx, upregulation of NF-κB and inflammatory cytokines, and apoptosis was observed in MIOX-Tg mice. Treatment of cells with ALOX-12 siRNA abolished gentamicin-mediated induction of cytokines and 12-HETE generation. HETE-12 treatment promoted this effect, along with upregulation of various signaling kinases and activation of GPCR31. Similarly, treatment of cells or mice with the ALOX-12 inhibitor ML355 attenuated inflammatory response, kinase signaling cascade, and albuminuria. Collectively, these studies highlight a potentially novel mechanism (i.e., the ROS/ALOX-12/12-HETE/GPR31 signaling axis) relevant to gentamicin-induced nephrotoxicity modulated by MIOX.

Renal Abnormalities Caused by Canine Distemper Virus Infection in Terminal Patients.

The aim of this study was to analyze the glomerular and tubular alterations in dogs with terminal distemper through light microscopy, immunofluorescence, and electron microscopy. Thirteen animals with a molecular diagnosis of distemper and neurological signs were selected. As a control group, 10 clinically healthy animals with no manifestations or signs of disease and with negative tests for Ehrlichia sp., Anaplasma sp., and Babesia sp. were included in this study. Renal tissue was evaluated by light microscopy, topochemistry for DNA/chromatin, and video image analysis to detect the nuclear phenotypes of the renal tubular epithelial cells (RTECs), immunofluorescence, and transmission electron microscopy. Results showed that dogs with distemper exhibited anemia, hypergammaglobulinemia, and proteinuria. Creatinine in the distemper group was lower compared to the control group (p = 0.0026), but there was no significant difference in relation to urea (p = 0.9876). Although this alteration may be due to the smaller muscle mass observed in animals with distemper, it probably is not of clinical importance. Glomerular and tubular lesions were confirmed by light microscopy in 84.6% of these animals. Additional findings in the animals with distemper included deposition of different classes of immunoglobulins, particularly IgM in 92.3% of the cases, fibrinogen deposition in 69.2% of the cases as assessed by immunofluorescence, alterations in the nuclear phenotypes of the RTEC characterized by condensation of chromatin, loss of DNA and reduction in the nuclear shape, and the presence of subendothelial and mesangial electron-dense deposits. These findings confirm the existence of renal alterations related to terminal distemper.

Histological evaluation of ischemic alterations in donors after cardiac death: A useful tool to predict post-transplant renal function.

Kidneys retrieved from donors after cardiac death (DCD) pose significant challenges from a clinical and technical point of view, undergoing a variable degree of ischemia-reperfusion injury. At present, the utilization of kidneys is assessed according to the Karpinski score, which does not take into account the ischemic insult and does not predict the functional recovery of the organ once transplanted. Therefore, the correlation between biopsy results and post-transplant graft function is still debated. In this study we examined kidney biopsies from DCD donors; we calculated the Karpinski score and subsequently identified and quantified the ischemic lesions in the glomerular, interstitial, and tubular compartments. These same lesions were quantified in kidney biopsies from donors after brain death (DBD) in a case-control analysis. The collected data were correlated with the clinical data of the donors and the post-transplant follow-up. Proximal tubule alterations are crucial in ischemia-reperfusion damage, showing precise histological alterations, which are more frequent in DCD than in DBD donors and are statistically correlated with functional recovery of the organ. Quantification of ischemic tubular lesions in biopsies of kidneys from DCD donors is a useful tool for predicting post-transplant renal function and a valid parameter for assessing the quality of the graft.

Serum homocysteine is associated with tubular interstitial lesions at the early stage of IgA nephropathy

BackgroundThe association between homocysteine (Hcy) and IgA nephropathy (IgAN) is not well understood. We aimed to investigate the relationship between Hcy and clinicopathologic features in IgAN patients.MethodsA total of 337 IgAN patients and 150 sex- and age- matched healthy controls were enrolled in this single-center retrospective study. According to Hcy ≤ 10 μmol/L or > 10 μmol/L, patients were divided into low and high Hcy groups. Multivariate logistic regression was performed to explore the risk factors for elevated Hcy.ResultsSerum Hcy was higher in IgAN patients than in healthy controls [11.6 (9.1,15.3) vs. 8.8 (7.5,10.6) μmol/L, P < 0.001], unanimously in the subgroup of 156 patients with a normal estimated glomerular filtration rate (eGFR) (≥ 90 ml/min/1.73 m2) [9.9 (7.6,12.4) vs. 8.8 (7.5,10.6) μmol/L, P < 0.001]. Compared to the low Hcy group, serum creatinine (Scr), blood urine nitrogen (BUN), uric acid (UA), endocapillary hypercellularity (E) and tubular atrophy/interstitial fibrosis lesion (T) were higher in the high Hcy group. Hcy levels were positively correlated with Scr, BUN, UA, 24-h urine protein, and E and T lesions, but negatively correlated with eGFR and superoxide dismutase (SOD). In the subgroup with normal eGFR, patients with higher Hcy were persistent with higher Scr, BUN and T lesions. A multivariate logistic regression model showed that the risk of elevated Hcy in patients with pathological T increased by 2.87-fold. T lesions could better predict high Hcy, with an odds ratio (OR) of 14.20 in the subgroup with normal eGFR.ConclusionsPathologic T was an independent risk factor associated with elevated Hcy, especially at the early stage of IgAN.

Can second-generation multitarget stool DNA panels reliably detect colorectal cancer and advanced precancerous lesions?

63 Background: Population-based colorectal cancer (CRC) screening can reduce mortality by detecting and removing advanced precancerous lesions (APL) and early-stage invasive disease. One guideline-included strategy is the multi-target stool DNA test (mt-sDNA), which combines detection of methylation DNA markers (MDMs), KRAS mutations, and fecal hemoglobin. Since the mt-sDNA pivotal study was conducted, novel biomarkers have been discovered. A panel of highly discriminant MDMs ( LASS4, LRRC4, PPP2R5C, and reference marker ZDHHC1) was identified through a blinded, case-control study of archival specimens. Here, we evaluated the performance of this novel mt-sDNA panel, combined with fecal hemoglobin, in archival stool samples weighted to early-stage CRC and prospectively collected APL, simulating a screening population. Methods: The verification study featured 777 samples—210 cases (112 CRC [49 stage I, 38 stage II, 17 stage III, and 8 stage IV] and 98 APL) and 567 controls (176 non-APL and 391 colonoscopy-negative)—from three trials (NCT01397747, NCT01260168, and NCT02503631). Median APL size was 12 mm (interquartile range: 10 mm to 15 mm), with 86.7% adenomas (n = 85) and 13.3% sessile serrated polyps (SSPs; n = 13). The average age was 65.5 years for cases (57% men) and 63.2 for controls (47% men). Samples were processed through homogenization, targeted MDM capture, bisulfite conversion, and MDM quantitation using Long‐probe Quantitative Amplified Signal (LQAS). Fecal hemoglobin was quantified using enzyme-linked immunosorbent assay (ELISA). Samples were split into stratified 75%/25% training-testing sets and model outcomes were cross-validated 1,000 times. Results: Mean performance from the cross-validation analysis is summarized in the table below. Overall sensitivity was 95.2% for CRC and 57.2% for APL, with specificities of 89.8% (no CRC/APL) and 92.4% (no neoplasia). Subgroup analyses showed high sensitivity for early-stage CRC, with 93.4% at stage I and 94.2% at stage II. By APL subtype, sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSPs. Conclusions: These data support high sensitivity and specificity for a second-generation mt-sDNA panel. A multicenter pivotal trial evaluating the panel is underway (NCT04144738). [Table: see text]

Glycosuria in primary glomerulopathies: prevalence and prognostic significance.

Introduction:Tubular damage is common in glomerular diseases (GD). Glycosuria is a marker of tubular dysfunction and may be used to detect tubular lesion and CKD progression. The aim of this study was to evaluate the prevalence and prognostic value of glycosuria at the time of diagnosis in primary glomerulopathies (PG).Methods: We conducted a 24-month retrospective study in patients diagnosed with PG in our center between 2009 and 2020. We excluded diabetic patients, use of SGLT2 inhibitors, transplant patients, and secondary GD. Patients were divided in two groups according to their glycosuria status at diagnosis.Results:We studied 115 patients. Global prevalence of glycosuria was 10% (n=11) and membranous nephropathy (MN) had the highest prevalence (n=5, 17.9%). We found that patients with glycosuria had higher serum creatinine (2.4 vs. 1.2 mg/dL, p=0.030), higher albuminuria (4.8 vs. 1.9 g/g, p=0.004), and lower serum albumin (2.3 vs. 3.2 g/dL, p=0.021). We did not find association with histological prognostic factors. At the end of follow-up, patients with glycosuria had higher prevalence of the composite outcome of stage 5D CKD or 50% increase in basal SCr (45.5% vs. 17.3%, p=0.037). In patients with MN, results were similar but we were able to find an association of glycosuria with more severe interstitial fibrosis and tubular atrophy (25.0 vs. 0.0 %, p=0.032).Conclusion: Ten percent of our patients with PG have glycosuria. Glycosuria at the time of diagnosis was associated with more severe clinical presentation and worst renal outcome. The association with higher albuminuria suggests that tubular function has an impact on the severity and outcomes of PG.

Tectorigenin protects against unilateral ureteral obstruction by inhibiting Smad3-mediated ferroptosis and fibrosis.

Renal tubular epithelial cell (TEC) injury and fibrosis are the key factors of the pathogenesis of chronic kidney disease. Here, we reported that tectorigenin is effectively protected against obstructive nephropathy established by unilateral ureteral obstruction (UUO). In vivo, tectorigenin administration significantly alleviated the deteriorations of renal functions including blood urea nitrogen and creatinine. Meanwhile, results from the histology suggested that renal injury characterized by tubular cell damage and fibrosis lesions of kidneys in UUO group were markedly attenuated following tectorigenin treatment. Mechanistically, we found that tectorigenin treatment greatly inhibited Smad3 phosphorylation, and the transcription and protein level of Nox4, a newly identified direct downstream molecule of Smad3 and a modulator of ferroptosis, while it indirectly restored the expression of glutathione peroxidase 4, a negative regulator of ferroptosis. Consistent with in vivo studies, treatment with tectorigenin also suppressed the ferroptosis induced by erastin/RSL3 and fibrosis stimulated by transforming growth factor β1 (TGF-β1) in primary renal TECs. What is more, treatment with ferroptosis inhibitor, ferrostatin-1, also impeded TGF-β1 stimulated the profibrotic effects in TECs, indicating that tectorigenin may relieve fibrosis by inhibiting ferroptosis in TECs. In addition, tectorigenin treatment exhibited a similar tendency, which inhibited Smad3 activation, and the docking analysis revealed that tectorigenin docked well into the Smad3 binding cavity with strong binding affinity (-7.9kcal/mol). Thus, this study deciphers the protective effect of tectorigenin against obstructive nephropathy through inhibiting Smad3-mediated ferroptosis and fibrosis.

Histomorphological assessment of non-neoplastic renal diseases at autopsy: an institutional experience in Southwestern Nigeria.

Autopsy remains an invaluable resource for medical education and establishing diagnosis of diseases that were missed prior to death. Many patients on admission in hospitals suffer kidney diseases that may contribute to their morbidity and/or mortality. The kidneys from autopsies provide opportunity to diagnose and understand some of these non-neoplastic renal lesions. This study aimed to present the frequency of non-neoplastic renal diseases at autopsy. We conducted a five-year retrospective review of post-mortem records of deceased who had autopsy. Data such as age, sex, cause of death, and kidney lesions were extracted from the post-mortem records and clinical details were gotten from the clinical summaries in the autopsy reports. The kidneys were examined for pathological findings that were then classified into glomerular, tubulointerstitial (tubulointerstitial nephritis and other tubular lesions such as tubular necrosis, casts and fibrosis) and vascular lesions. A total of seventy (70) cases met the inclusion criteria with 91.4% having significant non-neoplastic renal lesions. The mean age of the deceased was 57.7years (18years - 91years). Males accounted for 65.7% of the cases. Glomerular lesions were seen in 84.3% of the cases, tubulointerstitial nephritis in 41.6% of cases, vascular lesions were seen in 30% of the cases and other tubular lesions (such as stones, casts and tubular necrosis) were seen in 52.9% of the cases. Cardiovascular diseases and infections were the major causes of death in these patients, accounting for 40% and 27% respectively. Renal diseases were attributed to immediate cause of death in 10% of the cases. The kidney at autopsy provides a valuable renal pathology educational tool, as a wide range of medical renal lesions can be seen from kidneys examined at post mortem.

Abstract P168: Pretargeted radioimmunotherapy using 225Ac for intraperitoneal Her2-expressing epithelial ovarian carcinoma xenografts

Abstract Objectives Epithelial ovarian carcinoma (EOC) is a common and lethal gynecologic malignancy that frequently presents as advanced staged disease, such as peritoneal carcinomatosis (PC). We previously reported cures in BT-474 murine xenografts with Pretargeted Radioimmunotherapy (PRIT) using 177Lu radiohaptens targeting Her2 via a bispecific antibody (BsAb). Here-in we report the use of PRIT with alpha emitter 225Ac labelled PrDOTA to treat a PC model of SKOV3, a Her2+ cell line of EOC. Methods 6 wk old female athymic nude mice inoculated IP with 1E5 luciferase/GFP-transfected SKOV3 cells were separated into 5 groups (n=10). Treatment mice received 1 or 2 cycles of Anti-Her2-C825 BsAb + [225Ac]PrDOTA (Her2-Targeted), at 14 and 21 days after inoculation, respectively. Control groups received Anti-Her2 BsAb only, Anti-GPA33 BsAb + [225Ac]PrDOTA (Off-Targeted) or no treatment. On cycle day 1, the mice were injected IP with 0.25mg (1.19nmol) BsAb. On cycle day 2, 25µg (2.76nmol) CCA16-DOTAY clearing agent (CA) was given IV 22h from BsAb. Mice in therapy groups were injected IP with 1µCi (0.74-0.79nmol) [225Ac]PrDOTA-Bn 4h after CA. Weekly weights and BLIs with IP cavity ROIs were obtained and normalized to the respective values for each mouse at week 0 pre-treatment. End points: weight loss &amp;gt;20% baseline, moribund, or severe abdominal distension. At 154 days, 15 surviving treatment and 1 untreated control mice were submitted for hematology and histopathology. Results Histologic cures and prolonged survival were demonstrated in treatment mice (17/20 at 133 days) as compared to control mice (12/27 at 133 d, Logrank p&amp;lt;0.04). 3 mice from control groups were excluded due to BLI values &amp;lt;50% background in the first 3 weeks, suggesting no tumor burden. Tumors, as measured by normalized BLI values (nBLI), regressed in treatment mice when compared to control mice (2-way ANOVA p&amp;lt;0.01). nBLI values between treatment mice (1 and 2 cycles) and control mice (BsAb only, Off-target, no treatment) diverged at week 10 (Tukey’s test p&amp;lt;0.01). There was no difference in nBLI values between mice treated with 1 or 2 cycles of targeted PRIT (Tukey’s test p&amp;gt;0.05; all weeks). BLI of mice treated with 1 and 2 cycle of Her2 PRIT decreased 47% when compared to baseline within 1 week (T test p=0.04), suggesting treatment effects as early as 1 week. There were no differences in weights when compared to baseline (2-way ANOVA p&amp;gt;0.05). While the untreated mouse had high peritoneal adenocarcinoma tumor burden, there was no histologic evidence of viable neoplasia in 15/15 submitted treatment mice. Treatment mice had moderate renal tubular degenerative lesions on histology, but this did not affect renal function based on serum BUN or Cr. All hematologic parameters were within normal limits for treated mice. Conclusions 1 and 2 cycles of [225Ac]PrDOTA-PRIT against Her2 resulted in histologic cures and prolonged survival in IP SKOV3 xenografts with minimal toxicity. The anti-Her2 PrDOTA-PRIT system is a promising theranostic approach for otherwise incurable PC. Citation Format: Sebastian K. Chung, Christopher S. Chandler, Daniela Burnes Vargas, Shin H. Seo, Michael R. McDevitt, Darren Veach, Blesida Punzalan, Xu Hong, Hong-fen Guo, Garrett M. Nash, Andrea Cercek, Nai-Kong V. Cheung, Steven M. Larson, Sarah M. Cheal. Pretargeted radioimmunotherapy using 225Ac for intraperitoneal Her2-expressing epithelial ovarian carcinoma xenografts [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P168.

Prospective evaluation of the effectiveness of colonoscopic polyp resection

Background: Colon cancer incidence is on the rise and despite having undergone a colonoscopy to screen and remove all visible polyps as a preventive measure, nearly 1 in 110 patients will develop colon cancer within 3 years. The three main possible explanations for this are missing polyps, incompletely removed polyps, or rapidly growing tumors. Objective: To determine the proportion of colonic polyps ≤ 3 cm in size that show evidence of residual polyp tissue following colonoscopy and polypectomy. Methods: Patients who presented for colonoscopy at a community center were invited to participate in this study. Those who had confirmed adenoma were invited to repeat the procedure in 2 to 6 months with biopsies at the resection site to check for the presence of residual polyp tissue. Exclusion criteria included the absence of adenoma in the resected lesion, contraindication to polypectomy or follow-up colonoscopy, refusal to participate in follow-up examination, and other conditions increasing colon cancer risk. If polyps between 5 mm and 30 mm were found, the endoscopist resected them using the hot snare polypectomy technique or endoscopic mucosal resection (EMR). Results: Ninety-one patients completed the study protocol, with 105 lesions being studied. The second procedure was performed between 2 and 24 months. All analyzed lesions were adenoma, and three of them were associated with intramucosal adenocarcinoma. Others included 60 tubular lesions, 37 tubulovillous lesions, and 5 serrated lesions. Thirty-two lesions were flat and were removed by EMR; polypectomy was performed for 73 lesions. There was no residual tissue in the polypectomy group. The EMR group presented three cases of incomplete resection without adenocarcinomas. Conclusion: Our study showed that flat lesions might be an important cause of incomplete resection. In addition, we documented the complete resection of pedunculated lesions in all studied patients. This study provides more evidence to validate the empirical perception in the medical field that assumes the complete resection of pedunculated polyps. Therefore, we suggest that patients who undergo snare removal of pedunculated polyps should follow the regular protocol for colon cancer screening, with colonoscopy every 5 to 10 years. Meanwhile, the surveillance scheme should be reviewed for patients who undergo removal of flat lesions smaller than 30 mm.

Effect of Fc-Elabela-21 on renal ischemia/reperfusion injury in mice: Mediation of anti-apoptotic effect via Akt phosphorylation

IntroductionRenal ischemia/reperfusion injury (IRI) is the most common cause of acute kidney injury (AKI), and patients with AKI have a high rate of mortality. Apelin is a therapeutic candidate for treatment of IRI and Elabela (ELA) is a recently discovered hormone that also activates the apelin receptor (APJ). We examined the use of ELA as a preventive treatment for IRI using in vitro and in vivo models. MethodsMale mice were subjected to renal IRI, with or without administration of a stabilized form of ELA (Fc-ELA-21) for 4 days. Renal tubular lesions were measured using H&E staining, reactive oxygen species (ROS) were measured using a dihydroethidium stain assay, and renal cell apoptosis was measured using the TUNEL assay and flow cytometry. Immortalized human proximal tubular epithelial (HK-2) cells were pretreated with or without LY294002 and/or ELA-32, maintained at normoxic or hypoxic conditions, and then returned to normal culture conditions to mimic IRI. Cell apoptosis was determined using the TUNEL assay and cell proliferation was determined using the MTT assay. The levels of Akt, p-Akt, ERK1/2, p- ERK1/2, Bcl-2, Bax, caspase-3 and cleaved caspase-3 were measured using western blotting. ResultsFc-ELA-21 administration reduced renal tissue damage, ROS production, and apoptosis in mice that had renal IRI. ELA-32 reduced HK-2 cell apoptosis and restored the proliferation of cells subjected to IRI. Akt phosphorylation had a role in the anti-apoptotic effect of ELA. ConclusionThis study of in vitro and in vivo models of IRI indicated that the preventive and anti-apoptotic effects of ELA were mediated via the PI3K/Akt signaling pathway.

GATA3 Is a Useful Immunohistochemical Marker to Differentiate Variants of Renal Tubular Lesions from Different Segments of Renal Tubules

Abstract Introduction/Objective GATA3 is found in glomerular mesangial cells, and the distal tubules &amp; collecting ducts in metanephros and eventual kidneys, but not associated with the proximal tubules and loops of Henle. We hypothesize that GATA3 can be used as a marker to identify the origin of tubular differentiation in most renal tumors. Methods/Case Report Ten negative controls and 43 renal mass lesions (RCC, papillary, clear cell papillary, and chromophobe carcinomas, oncocytoma, and polycystic kidney disease). GATA3 nuclear stain was graded as negative (absent stain), equivocal and positive (&amp;lt; 5 and &amp;gt; 5% cells, respectively). Details of their GATA3 nuclear expression was analyzed for identifying their tubular segmental origins. Results (if a Case Study enter NA) In 10 normal renal parenchyma, GATA3 was positive in mesangial cells, distal tubules, and collecting ducts, but was negative in the proximal tubules and loop of Henle. The cystic lining of glomerulocystic renal disease was stained negatively for GATA3 (proximal tubular origin), whereas pediatric and adult variants of polycystic kidney diseases was positive for GATA3 staining (distal tubular origin). 1/10 ten clear cell RCC and papillary RCC showed focal positive GATA3 stain. GATA3 showed weakly positive staining in some oncocytomas (4/11) and some chromophobe RCC (4/11), indicating that they might be derived from the junctional segment between the loop of Henle and the distal tubules. By contrast, all clear cell papillary RCC (distal tubule origin) were diffusely positive. Conclusion Our results indicate that GATA3 is a useful immunohistochemical marker to determine the developmental origin in the specific renal tubular segment for the majority of renal mass lesions. Thus, it may be useful for routine differential diagnosis of these lesions.

Native oesophageal mucocoele: A rare complication of double exclusion of oesophagus.

Introduction and importanceNative oesophageal mucocoele usually follows bipolar exclusion of oesophagus for various reasons and is very rare in literature. Though mostly asymptomatic, its symptoms can be divided into 3 groups – Compressive, Infective and fistulizing symptoms. The management options described in the literature are percutaneous drainage, chemical ablation, esophagectomy and internal drainage using Roux-en-Y reconstruction.Case reportA 40 year old female, presented with complaints of dysphagia, weight loss and chest pain for 6 month. She had history of retrosternal gastric pull-up for oesophageal stricture following corrosive injury. On evaluation with CT chest, there was a well-defined fluid attenuated tubular elongated lesion in the mediastinum in the region of oesophagus which was non-opacified with oral contrast and a diagnosis of giant oesophageal mucocoele was made. She underwent internal drainage of mucocoele by roux-en-Y esophagojejunostomy with placement of transanastomotic drain and discharged with an uneventful recovery with the trans-anastomotic drain in situ, which was removed on outpatient basis. Now she is asymptomatic in the subsequent follow up.Clinical discussion and conclusionThough rare, mucocoele of oesophagus can lead to life threatening complication like respiratory distress, sepsis. Its diagnosis requires high index of suspicion and CT chest is helpful. Management options depend upon nutritional status of the patient and associated co-morbidities. Esophagectomy is the definitive form of treatment but not always possible and other options can be internal or percutaneous drainage.

Clinical features of colorectal duplication in children: A study of 25 cases

PurposeTo describe the clinical features and surgical management of pediatric colorectal duplication. MethodsTwenty-five patients with colorectal duplication at Beijing Children's Hospital between January 2010 and December 2020 were reviewed. Colorectal duplications were divided into cystic, diverticular, tubular and mixed types according to shape. ResultsOf the patients, 64% were female, and 44% had accompanying malformations. Abnormal prenatal ultrasound findings (24%), abnormalities immediately found after birth (28%), and postnatal subjective symptoms (48%) were the main clinical presentations. Cystic lesions were observed in 16 patients (64%), including 12 in the colon and 4 in the rectum. Diverticular lesions were observed in 4 patients (16%), and all originated from the sigmoid colon. Among the 4 patients (16%) with tubular lesions, 3 involved the total colon, and the other originated from the splenic flexure to the proximal sigmoid colon. The patient with mixed duplication presented an intact enteric cyst within tubular duplication of the total colon. The mean age at surgery was 20 (0.3–130) months. Except for 4 total colon duplications, complete surgical resection of duplication lesions was performed in all patients. The “distal cross-section, mucosa stripping, and closure” procedure was performed in 3 patients with total colon duplication. Eighteen patients (72%) were followed up for a median time of 54.5 (5–129) months and recovered uneventfully. ConclusionsOwing to various clinical presentations, colorectal duplication requires careful preoperative differential diagnosis. Complete surgical resection is the preferred radical method for treating cystic, diverticular and short tubular colorectal duplications, except for total colon duplications. Level of EvidenceLevel IV.

Urinary neutrophil gelatinase-associated lipocalin—an early biomarker for renal injury in patients with beta-thalassemia major

INTRODUCTION : The iron overload and the development of secondary hemosiderosis in patients with β-thalassemia major (β-TM) lead to organ damages, including kidney disorders from early childhood. Contemporary urinary markers such as neutrophil gelatinase-association lipocalin (NGAL), β2-microglobulin (β2-MG), and N-acetyl-β-D-glucosaminidase (NAG) could be a useful tool for clinicians in diagnosis of early tubular lesions. AIM : The aim of this article is to make an assessment of contemporary urine biomarkers β2-microglobulin, neutrophil gelatinase-associated lipocalin, and N-acetyl-beta-D-glucosaminidase in the diagnosis of early renal injury in patients with β-TM. MATERIALS AND METHODS : The current study was conducted by examining 44 patients with β-thalassemia major and 30 controls. All participants were tested for NGAL, β2-MG, and NAG in the first sample morning urine using ELISA method. RESULTS : The results show statistically significant differences between the two examined groups in urinary NGAL. CONCLUSION : Urinary NGAL indicates subclinical kidney injury when the tubular reabsorption of molecules is impaired.

Tubular injury in diabetic ketoacidosis: Results from the diabetic kidney alarm study.

Glomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D). Blood and urine samples were collected from 40 children with DKA (52% boys, mean age 11 ± 4 years, venous pH7.2 ± 0.1, glucose 451 ± 163 mg/dL) at three timepoints: 0-8 and 12-24 h after starting insulin, and 3 months after discharge. Mixed-effects models evaluated the changes in tubular injury markers over time (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1 [KIM-1], and interleukin 18 [IL-18]). We also evaluated the relationships among the tubular injury biomarkers, copeptin, a vasopressin surrogate, and serum uric acid (SUA). Serum NGAL, KIM-1, and IL-18 were highest at 0-8h (306.5 ± 45.9ng/mL, 128.9 ± 10.1pg/mL, and 564.3 ± 39.2pg/mL, respectively) and significantly decreased over 3 months (p=0.03, p=0.01, and p < 0.001, respectively). There were strong relationships among increases in copeptin and SUA and rises in tubular injury biomarkers. At 0-8h, participants with acute kidney injury (AKI) [17%] showed significantly higher concentrations of tubular injury markers, copeptin, and SUA. DKA was characterized by tubular injury, and the degree of injury associated with elevated copeptin and SUA. Tubular injury biomarkers, copeptin and SUA may be able to predict AKI in DKA.

When COVID-19 delays the management of an urgent heart condition: A rare case of a spontaneous dissection of two coronary arteries.

Some severe life‐threatening conditions could be misdiagnosed during the current COVID‐19 pandemic.

Atypical histological abnormalities in an adult patient with nephronophthisis harboring NPHP1 deletion: a case report

BackgroundNephronophthisis (NPHP) is a chronic tubular interstitial disorder that exhibits an autosomal recessive genetic form and causes progressive renal failure in children. Patients with NPHP rarely show urinary abnormalities, edema, or hypertension. Thus, NPHP is often detected only when renal failure becomes advanced. NPHP can be divided into three types based on the age of end-stage renal failure, i.e., infant type (approximately 5 years old), juvenile type (approximately 13–14 years old), and adolescent type (approximately 19 years old). Here, we report a case of NPHP diagnosed by genetic analysis at 26 years of age with atypical histological abnormalities.Case presentationA 26-year-old woman showed no growth disorders or urinary abnormalities in annual school physical examinations. However, at a check-up at 26 years old, she exhibited renal dysfunction (eGFR 26 mL/min/1.73 m2). Urine tests indicated low specific gravity of urine, but not proteinuria or microscopic hematuria. Urinary β2-microglobulin was high (805 μg/L), and renal biopsy was performed for definitive diagnosis. Histological findings showed no significant findings in glomeruli. However, moderate fibrosis was observed in the interstitial area, and moderate atrophy was observed in the tubules. There were no significant findings in immunofluorescence analysis, and no electron dense deposits were detected by electron microscopy. Although cyst-like expansion of the tubules was unclear, tubular atrophy was dominantly found in the distal tubule by cytokeratin 7 staining. Genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP.ConclusionsNPHP is not merely a pediatric disease and is relatively high incidence in patients with adult onset end-stage of renal disease. In this case, typical histological abnormalities, such as cyst-like expansion of the tubular lesion, were not observed, and diagnosis was achieved by genetic analysis of the NPHP1 gene, which is responsible for the onset of NPHP. In patients with renal failure with tubular interstitial disease dominantly in the distal tubules, it is necessary to discriminate NPHP, even in adult cases.

Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension.

Renal and cardiac impairments are frequent events in the presence of hypertension. Organ damage is mainly linked to oxidative stress due to high blood pressure and may be reduced by antioxidant supplementation. Alpha-lipoic acid (ALA) is one of most effective antioxidants. It is widely used as a nutritional supplement in a racemic mixture (+/–), even though the (+)-enantiomer is biologically active. This study was designed to investigate the effect of treatment with (+/–)-ALA and its enantiomers on renal and heart parenchyma in spontaneously hypertensive rats (SHR), using immunochemical and immunohistochemical techniques. The results confirmed that the oxidative mechanisms of organ alterations, due to hypertension, and characterized by glomerular and tubular lesions, left ventricular hypertrophy, and fibrosis but not by apoptosis were accompanied by proteins’ and nucleic acids’ oxidation. We found greater effectiveness of (+)-ALA compared to (+/−)-ALA in reducing oxidative stress, cardiac and renal damages in SHR. To conclude, these data propose (+)-ALA as one of the more appropriate antioxidant molecules to prevent renal and cardiac alterations associated with hypertension.