Interleukin-1ß/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer-An Exploratory Analysis of Clinical and Tumor Biological Significance.

Previous data indicate a role of IL-1 and IL-1RA imbalance in bladder carcinoma (BC); the inhibition of IL-1 signaling might be considered a treatment option. Objective: To assess expression patterns and the prognostic role of IL-1ß and IL-1RA in invasive BC and to evaluate their interaction with AKT signaling and proliferation. The study included two independent cohorts of n = 92 and n = 102 patients who underwent a radical cystectomy for BC. Specimen from BC and benign urothelium (n = 22 and n = 39) were processed to a tissue microarray and immunohistochemically stained for IL-1ß, IL-1RA, AKT, and Ki-67. Expression scores were correlated to clinical variables and Ki-67 and AKT expression. An association with outcome was assessed using Wilcoxon Kruskal-Wallis tests, Chi-square tests or linear regression, dependent on the variable's category. Kaplan-Meier and Cox proportional hazard analyses were used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Both IL-1ß and IL-1RA were significantly overexpressed in invasive BC compared to benign urothelium in both cohorts (p < 0.005). IL-1ß was associated with vascular invasion (210 vs. 183, p < 0.02), lymphatic invasion (210 vs. 180, <0.05) and G3 cancer (192 vs. 188, <0.04). The survival analysis revealed favorable RFS, CSS, and OS in the case of high IL-1ß expression (p < 0.02, <0.03, and <0.006, respectively). Multivariate analyses revealed an independent impact of (low) IL1ß expression on RFS, CSS, and OS. The IL-1ß and IL-1ß/IL-1RA ratios were positively correlated to the AKT expression (p < 0.05 and <0.01, respectively). Additionally, the high expression of Ki-67 (>15%) correlated with higher levels of IL-1ß (p = 0.01). The overexpression of IL-1ß and IL-1RA is frequently found in BC, with a prognostic significance observed for the IL-1ß protein expression. The observed link between the IL-1ß/IL-1RA axis and AKT signaling may indicate possible autophagy activation processes besides the known tumor-promoting effects of AKT.

How to treat jatrogenic ureteral injury after posterior spinal surgery? Case report and review of literature.

Introduction: Entry into the retroperitoneal space during open posterior spinal surgery introduces the rare possibility of iatrogenic ureteral injury. Case presentation: We describe a case of ureteral injury after spinal surgery in a 49-year-old female with persistent lumbar pain and high fever 2 weeks after spinal surgery. After admission to the urology department, a computer tomography scan was performed and revealed right-side hydronephrosis grade III and large retroperitoneal fluid collection. After radiological confirmation of right ureteral injury, a ureteral stent was placed, but 4 weeks later, ureteral stricture was confirmed on antegrade pyelography. Therefore, surgical ureteroplasty was indicated 2 months after initial admission to the urology department. Six weeks later, the stent was removed, and intravenous pyelography revealed a normal ureteral passage. Conclusion: There should be a low threshold for ureteral injuries after spinal cord surgery in patients with high fever and elevated blood creatinine levels.

Mini-laparotomy radical cystectomy with limited bowel externalization during ileal conduit urinary diversion reduces the rate of postoperative complications: a match-paired, single centered analysis.

OBJECTIVE: To assess the feasibility and functional outcomes of mini-laparotomy radical cystectomy (RC) in association with limited bowel externalization during ileal conduit urinary diversion. METHODS: Between January 2018 and March 2020, 53 patients underwent RC plus pelvic lymph node dissection (PLND) for invasive carcinoma of the urinary bladder. This group of patients was intentionally treated utilizing the mini-laparotomy approach, with the addition of limited bowel externalization during conduit preparation and match-paired with 46 examinees from a historical series of patients who underwent conventional open RC plus PLND and ileal conduit diversion. Clinicopathological features and perioperative outcomes were examined from medical records, while postoperative pain was evaluated through the Visual Analog Scale for Pain (VAS). Mean pain scores were evaluated on postoperative days (POD) 1-3. RESULTS: There was no difference in specific intraoperative complications between groups, with a median (range) incision length of 8 (5-10) cm within the first group and 16.3 (12-22.6) cm within the second group. The first group had less postoperative pain compared with patients in the second group, with mean pain scores significantly lower across POD 1-3, 3.8 (IQR: 0-6) versus 6.7 (IQR: 3.8-8.1) and 2.5 (IQR: 1-3.7) versus 4.6 (IQR: 3-6), respectively (p = .012 and .002). CONCLUSIONS: By using this technique, we were able to significantly reduce patients' postoperative pain, time to bowel restitution, and hospital stay, which are major issues in minimizing short-term postoperative complications of conventional open surgery.

'Burned-Out' primary testicular tumour: Is retroperitoneal lymph node biopsy mandatory prior to initiation of chemotherapy? Report of three cases and a review of the literature.

The term 'burned-out' tumour of the testis describes a spontaneously and completely regressed testicular tumour that presents at the stage of metastasis. We report three cases of burned-out testicular tumour to illustrate their clinical, radiological and histopathological features and to discuss the hypothesis of the efficacy of early adjuvant chemotherapy without a previous retroperitoneal lymph node biopsy. Subsequent to radical orchiectomy, each pathohistology report revealed testicular hypotrophy or microcalcifications, with no clearly visible germ cell tumours within the specimen. Additionally, following surgery, the patients received the standard (cisplatin-etoposide-bleomycin) chemotherapy protocol, which in two out of three cases showed a complete response. Only one examinee revealed a partial response and received salvage chemotherapy, but he remained in the remission phase during the last follow-up. This study illustrates the value of the early administration of adjuvant chemotherapy in patients with burned-out testicular tumour, which offers the possibility of omitting the diagnostic retroperitoneal lymph node biopsy. Considering the low threshold for testicular malignancy, it is clearly of the utmost importance that these rare patients be treated in a timely manner and without adjunctive procedures (lymph node biopsy) leading to additional morbidity.

Technique selection of ureteroileal anastomosis in hautmann ileal neobladder with chimney modification: Reliability of patient-based selection strategy and its impact on ureteroentric stricture rate.

OBJECTIVE: We aimed to establish the reliability of technique selection strategy for ureteroileal anastomosis (Bricker vs. Wallace) by comparing perioperative outcomes, complications, and anastomotic stricture rate in a contemporary series of patients who underwent open radical cystectomy followed by reconstruction of modified Hautmann neobladder. MATERIALS AND METHODS: A total of 60 patients underwent radical cystectomy and modified Hautmann neobladder, of whom 30 patients (group I) with Bricker anastomotic technique were compared to 30 matched paired patients with end-to-end ureteroileal anastomosis (group II). Long-term results, including ureteroileal stricture (UIS) and postoperative complication rate at two year follow up were available. The choice of anastomosis type was successively based on chimney size, ureteral length after retro-sigmoidal tunneling and diameter of distal ureter. Postoperative complications were graded according to the Clavien-Dindo system. RESULTS: Ureteroileal stricture rate was 6.6% in group I vs. 0% in group II, after three months (p < 0.05), while anastomotic leakage rate was 6.6% vs. 3.3% (group I vs group II) between the two groups for the same follow up period (p > 0.05). High-grade complications (Clavien III-V) were more in Bricker group as compared to Wallace group and the difference was significant (20% vs 10.3%, p = 0.03). CONCLUSION: Our preliminary outcomes demonstrate that this selection strategy seems to be clinically reliable, with lower incidence of postoperative complications in Wallace group.

Mepolizumab targets multiple immune cells in aspirin-exacerbated respiratory disease.

BACKGROUND: Eosinophilic asthma and nasal polyposis are hallmarks of aspirin-exacerbated respiratory disease (AERD), and IL-5 inhibition has been shown to provide therapeutic benefit. However, IL-5Rα is expressed on many cells in addition to eosinophils, and the mechanisms by which IL-5 inhibition leads to clinical benefit in eosinophilic asthma and nasal polyposis are unlikely to be due exclusively to antieosinophil effects. OBJECTIVE: We sought to identify the mechanisms by which anti-IL-5 treatment with mepolizumab improves respiratory inflammation in AERD. METHODS: The clinical characteristics, circulating granulocytes, nasal scraping transcripts, eosinophilic cationic protein, tryptase, and antibody levels, and urinary and nasal eicosanoid levels were measured for 18 subjects with AERD who were taking mepolizumab and compared with those of 18 matched subjects with AERD who were not taking mepolizumab. RESULTS: Subjects taking mepolizumab had significantly fewer peripheral blood eosinophils and basophils, and those cells that remained had higher surface CRTH2 expression than did the cells from subjects not taking mepolizumab. Nasal prostaglandin F2α, prostaglandin D2 metabolites, leukotriene B4, and thromboxane levels were lower in subjects taking mepolizumab, as were urinary levels of tetranor-prostaglandin D2 and leukotriene E4. The nasal epithelial cell transcripts that were overexpressed among subjects with AERD who were taking mepolizumab were enriched for genes involved in tight junction formation and cilium organization. Nasal and urinary prostaglandin E2, tryptase, and antibody levels were not different between the 2 groups. CONCLUSION: IL-5 inhibition in AERD decreases production of inflammatory eicosanoids and upregulates tight junction-associated nasal epithelial cell transcripts, likely due to decreased IL-5 signaling on tissue mast cells, eosinophils, and epithelial cells. These direct effects on multiple relevant immune cells contribute to the mechanism of benefit afforded by mepolizumab.

Functional results of hautmann neobladder with chimney modification and wallace ureteroileal anastomosis: initial experience with 22 patients

ABSTRACT Objective: To assess the functional outcomes and complications of modified Hautmann neobladder with Wallace ureteroileal anastomosis on a 6-8 cm long isoperistaltic chimney, following radical cystectomy. Materials and Methods: Between January 2015 and October 2019, 22 patients (18 men and 4 women) underwent radical cystectomy and Hautmann neobladder reconstruction with chimney modification and Wallace I ureteroileal anastomosis. The mean age of patients was 61 years (45-74 years). All procedures were performed by the same surgeon and the mean follow-up was 29.4 months. Complications were registered as early (occurring within 3 months) or late (occurring after 3 months), with particular attention addressed to the ureteroileal anastomotic stricture and anastomotic leakage rate. Patient evaluation also included symptom analysis for daytime continence and voiding frequency. Results: Ureteroileal anastomotic stricture was not detected as a cause of hydronephrosis. Hovewer, the anastomotic leakage occurred in one patient during the early postoperative period. Early complications occurred in 9 patients and the most common was bilateral hydronephrosis, detected in 5 examinees. Late complications occurred in 4 patients. Complete daytime and nighttime continence achieved in 18 and 16 patients respectively, with two patients (9%) still required intermittent catheterization three months after surgery. Conclusions: The functional results with modified Hautmann neobladder, incorporating short afferent limb in Wallace I uretero-enteric anastomosis, were efficient. This technique is an effective way to minimize potential uretero-enteric stricture, anastomotic leakage and incidence of vesicoureteral reflux.

Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation.

Mast cells (MCs) play a pathobiologic role in type 2 (T2) allergic inflammatory diseases of the airway, including asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Distinct MC subsets infiltrate the airway mucosa in T2 disease, including subepithelial MCs expressing the proteases tryptase and chymase (MCTC) and epithelial MCs expressing tryptase without chymase (MCT). However, mechanisms underlying MC expansion and the transcriptional programs underlying their heterogeneity are poorly understood. Here, we use flow cytometry and single-cell RNA-sequencing (scRNA-seq) to conduct a comprehensive analysis of human MC hyperplasia in CRSwNP, a T2 cytokine-mediated inflammatory disease. We link discrete cell surface phenotypes to the distinct transcriptomes of CRSwNP MCT and MCTC, which represent polarized ends of a transcriptional gradient of nasal polyp MCs. We find a subepithelial population of CD38highCD117high MCs that is markedly expanded during T2 inflammation. These CD38highCD117high MCs exhibit an intermediate phenotype relative to the expanded MCT and MCTC subsets. CD38highCD117high MCs are distinct from circulating MC progenitors and are enriched for proliferation, which is markedly increased in CRSwNP patients with aspirin-exacerbated respiratory disease, a severe disease subset characterized by increased MC burden and elevated MC activation. We observe that MCs expressing a polyp MCT-like effector program are also found within the lung during fibrotic diseases and asthma, and further identify marked differences between MCTC in nasal polyps and skin. These results indicate that MCs display distinct inflammation-associated effector programs and suggest that in situ MC proliferation is a major component of MC hyperplasia in human T2 inflammation.

Functional results of hautmann neobladder with chimney modification and wallace ureteroileal anastomosis: initial experience with 22 patients.

OBJECTIVE: To assess the functional outcomes and complications of modified Hautmann neobladder with Wallace ureteroileal anastomosis on a 6-8 cm long isoperistaltic chimney, following radical cystectomy. MATERIALS AND METHODS: Between January 2015 and October 2019, 22 patients (18 men and 4 women) underwent radical cystectomy and Hautmann neobladder reconstruction with chimney modification and Wallace I ureteroileal anastomosis. The mean age of patients was 61 years (45-74 years). All procedures were performed by the same surgeon and the mean follow-up was 29.4 months. Complications were registered as early (occurring within 3 months) or late (occurring after 3 months), with particular attention addressed to the ureteroileal anastomotic stricture and anastomotic leakage rate. Patient evaluation also included symptom analysis for daytime continence and voiding frequency. RESULTS: Ureteroileal anastomotic stricture was not detected as a cause of hydronephrosis. Hovewer, the anastomotic leakage occurred in one patient during the early postoperative period. Early complications occurred in 9 patients and the most common was bilateral hydronephrosis, detected in 5 examinees. Late complications occurred in 4 patients. Complete daytime and nighttime continence achieved in 18 and 16 patients respectively, with two patients (9%) still required intermittent catheterization three months after surgery. CONCLUSIONS: The functional results with modified Hautmann neobladder, incorporating short afferent limb in Wallace I uretero-enteric anastomosis, were efficient. This technique is an effective way to minimize potential uretero-enteric stricture, anastomotic leakage and incidence of vesicoureteral reflux.

Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential.

Barrier tissue immune responses are regulated in part by nociceptors. Nociceptor ablation alters local immune responses at peripheral sites and within draining lymph nodes (LNs). The mechanisms and significance of nociceptor-dependent modulation of LN function are unknown. Using high-resolution imaging, viral tracing, single-cell transcriptomics, and optogenetics, we identified and functionally tested a sensory neuro-immune circuit that is responsive to lymph-borne inflammatory signals. Transcriptomics profiling revealed that multiple sensory neuron subsets, predominantly peptidergic nociceptors, innervate LNs, distinct from those innervating surrounding skin. To uncover LN-resident cells that may interact with LN-innervating sensory neurons, we generated a LN single-cell transcriptomics atlas and nominated nociceptor target populations and interaction modalities. Optogenetic stimulation of LN-innervating sensory fibers triggered rapid transcriptional changes in the predicted interacting cell types, particularly endothelium, stromal cells, and innate leukocytes. Thus, a unique population of sensory neurons monitors peripheral LNs and may locally regulate gene expression.

Modified Wallace anastomotic technique reduces ureteroenteric stricture rates after ileal conduit urinary diversion

ABSTRACT Purpose: To compare perioperative outcomes, complications and anastomotic stricture rate in a contemporary series of patients who underwent open radical cystectomy (RC) with modified Wallace anastomotic technique versus traditional ileal conduit. Materials and methods: Study enrolled 180 patients, of whom 140 were randomized and underwent RC; seventy were randomized to group I and the seventy to the group II. For the primary objective, we hypothesized that the rate of ureteroenteric strictures would be at least 20 % lower in the second group. Secondary end points included rate of anastomotic leak, surgical time, deterioration of the upper tract, intraoperative blood loss and patient-reported quality of life (HRQOL). The modified Wallace 1 technique involved eversion of the ureteral plate and bowel mucosa edges, which were anastomosed together in running fashion, while the outher anastomotic wall was augmented with sero-serosal interrupted sutures. Results: The mean (SD) follow-up time was 26.1 (5.7) months in group I and 25.2 (4.8) months in group II, during which, anastomotic stricture was observed in 8 patients (12%) from the first and 2 patients (3%) from the second group (p < 0.05). The anastomotic leakage rate was significantly higher in first group (17% vs. 8.5%, p< 0.05), while patient-reported HRQOL outcomes were similar between groups after the 12 month follow-up period. Conclusions: By using a modified Wallace technique, we were able to significantly lower anastomotic stricture and anastomotic leakage rates, which are major issues in minimizing both short- and long-term postoperative complications.

Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn's Disease.

BACKGROUND & AIMS: Studies are needed to determine the mechanisms of mucosal dysregulation in patients with inflammatory bowel diseases (IBDs) and differences in inflammatory responses of patients with ulcerative colitis (UC) vs Crohn's disease (CD). We used mass cytometry (CyTOF) to characterize and compare immune cell populations in the mucosa and blood from patients with IBD and without IBD (controls) at single-cell resolution. METHODS: We performed CyTOF analysis of colonic mucosa samples (n = 87) and peripheral blood mononuclear cells (n = 85) from patients with active or inactive UC or CD and controls. We also performed single-cell RNA sequencing, flow cytometry, and RNA in situ hybridization analyses to validate key findings. We used random forest modeling to identify differences in signatures across subject groups. RESULTS: Compared with controls, colonic mucosa samples from patients with IBD had increased abundances of HLA-DR+CD38+ T cells, including T-regulatory cells that produce inflammatory cytokines; CXCR3+ plasmablasts; and IL1B+ macrophages and monocytes. Colonic mucosa samples from patients with UC were characterized by expansion of IL17A+ CD161+ effector memory T cells and IL17A+ T-regulatory cells; expansion of HLA-DR+CD56+ granulocytes; and reductions in type 3 innate lymphoid cells. Mucosal samples from patients with active CD were characterized by IL1B+HLA-DR+CD38+ T cells, IL1B+TNF+IFNG+ naïve B cells, IL1B+ dendritic cells (DCs), and IL1B+ plasmacytoid DCs. Peripheral blood mononuclear cells from patients with active CD differed from those of active UC in that the peripheral blood mononuclear cells from patients with CD had increased IL1B+ T-regulatory cells, IL1B+ DCs and IL1B+ plasmacytoid DCs, IL1B+ monocytes, and fewer group 1 innate lymphoid cells. Random forest modeling differentiated active UC from active CD in colonic mucosa and blood samples; top discriminating features included many of the cellular populations identified above. CONCLUSIONS: We used single-cell technologies to identify immune cell populations specific to mucosa and blood samples from patients with active or inactive CD and UC and controls. This information might be used to develop therapies that target specific cell populations in patients with different types of IBD.

Modified wallace anastomotic technique reduces ureteroenteric stricture rates after ileal conduit urinary diversion.

PURPOSE: To compare perioperative outcomes, complications and anastomotic stricture rate in a contemporary series of patients who underwent open radical cystectomy (RC) with modified Wallace anastomotic technique versus traditional ileal conduit. MATERIALS AND METHODS: Study enrolled 180 patients, of whom 140 were randomized and underwent RC; seventy were randomized to group I and the seventy to the group II. For the primary objective, we hypothesized that the rate of ureteroenteric strictures would be at least 20 % lower in the second group. Secondary end points included rate of anastomotic leak, surgical time, deterioration of the upper tract, intraoperative blood loss and patient-reported quality of life (HRQOL). The modified Wallace 1 technique involved eversion of the ureteral plate and bowel mucosa edges, which were anastomosed together in running fashion, while the outher anastomotic wall was augmented with sero-serosal interrupted sutures. RESULTS: The mean (SD) follow-up time was 26.1 (5.7) months in group I and 25.2 (4.8) months in group II, during which, anastomotic stricture was observed in 8 patients (12%) from the first and 2 patients (3%) from the second group (p < 0.05). The anastomotic leakage rate was significantly higher in first group (17% vs. 8.5%, p < 0.05), while patient-reported HRQOL outcomes were similar between groups after the 12 month follow-up period. CONCLUSIONS: By using a modified Wallace technique, we were able to significantly lower anastomotic stricture and anastomotic leakage rates, which are major issues in minimizing both short- and long-term postoperative complications.

IL-5Rα marks nasal polyp IgG4- and IgE-expressing cells in aspirin-exacerbated respiratory disease.

BACKGROUND: The cause of severe nasal polyposis in aspirin-exacerbated respiratory disease (AERD) is unknown. Elevated antibody levels have been associated with disease severity in nasal polyps, but upstream drivers of local antibody production in nasal polyps are undetermined. OBJECTIVE: We sought to identify upstream drivers and phenotypic properties of local antibody-expressing cells in nasal polyps from subjects with AERD. METHODS: Sinus tissue was obtained from subjects with AERD, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps, and controls without CRS. Tissue antibody levels were quantified via ELISA and immunohistochemistry and were correlated with disease severity. Antibody-expressing cells were profiled with single-cell RNA sequencing, flow cytometry, and immunofluorescence, with IL-5Rα function determined through IL-5 stimulation and subsequent RNA sequencing and quantitative PCR. RESULTS: Tissue IgE and IgG4 levels were elevated in AERD compared with in controls (P < .01 for IgE and P < .001 for IgG4 vs CRSwNP). Subjects with AERD whose nasal polyps recurred rapidly had higher IgE levels than did subjects with AERD, with slower regrowth (P = .005). Single-cell RNA sequencing revealed increased IL5RA, IGHG4, and IGHE in antibody-expressing cells from patients with AERD compared with antibody-expressing cells from patients with CRSwNP. There were more IL-5Rα+ plasma cells in the polyp tissue from those with AERD than in polyp tissue from those with CRSwNP (P = .026). IL-5 stimulation of plasma cells in vitro induced changes in a distinct set of transcripts. CONCLUSIONS: Our study identifies an increase in antibody-expressing cells in AERD defined by transcript enrichment of IL5RA and IGHG4 or IGHE, with confirmed surface expression of IL-5Rα and functional IL-5 signaling. Tissue IgE and IgG4 levels are elevated in AERD, and higher IgE levels are associated with faster nasal polyp regrowth. Our findings suggest a role for IL-5Rα+ antibody-expressing cells in facilitating local antibody production and severe nasal polyps in AERD.

Running suture hemostatic technique versus standard reconstruction of the surgical bed in Zero - Ischemia Time mini-flank Open Partial Nephrectomies. Retrospective, Match-Paired Case-Control Study.

OBJECTIVE: To estimate the efficacy of our technique of zero ischemia time partial nephrectomy (ZTPN) with hemostatic running suture and compare it to the standard technique, in terms of perioperative complications, operative time (OT) and estimated blood loss (EBL). MATERIALS AND METHODS: We retrospectively analysed 180 consecutive patients who underwent ZTPN using a supra 11th or supra 12th rib mini flank approach. First group numbered 90 patients treated with running suture hemostatic technique (RSHT), while the control group enrolled 90 patients in whom we performed standard reconstruction technique (SRT). According the propensity score, both groups were similar in terms of tumor size, age and PADUA score. Patients with solitary tumour limited to the kidney (T1-T2a) were included. Our technique included a running suture of surgical bed edges and closure of the renal cortex by the positioning of peri-renal fat within the cortical bed and fixation with interrupted sutures. RESULTS: PADUA score and tumor size were comparable between groups (7.12 ± 1.33 vs 7.1 ± 2.11, p = 0.4 and 52.9 ± 14.8 vs 50.0 ± 13.2, p = 0.3). The mean operative time (OT) was significantly longer in first group (165.2 vs 95, p = 0.04), while median estimated blood loss (EBL) was significantly reduced (250 vs 460 ml, p = 0.02). Surgical resection margins were negative in 100% of cases and no patient developed a local or distant recurrence during follow up. There was significant difference in postoperative GFR value between groups (p < 0.05). CONCLUSIONS: Our technique could be safely performed in local, low volume facilities, thus reducing the need for expensive and more challenging minimal invasive surgical techniques..

Allergic inflammatory memory in human respiratory epithelial progenitor cells.

Barrier tissue dysfunction is a fundamental feature of chronic human inflammatory diseases1. Specialized subsets of epithelial cells-including secretory and ciliated cells-differentiate from basal stem cells to collectively protect the upper airway2-4. Allergic inflammation can develop from persistent activation5 of type 2 immunity6 in the upper airway, resulting in chronic rhinosinusitis, which ranges in severity from rhinitis to severe nasal polyps7. Basal cell hyperplasia is a hallmark of severe disease7-9, but it is not known how these progenitor cells2,10,11 contribute to clinical presentation and barrier tissue dysfunction in humans. Here we profile primary human surgical chronic rhinosinusitis samples (18,036 cells, n = 12) that span the disease spectrum using Seq-Well for massively parallel single-cell RNA sequencing12, report transcriptomes for human respiratory epithelial, immune and stromal cell types and subsets from a type 2 inflammatory disease, and map key mediators. By comparison with nasal scrapings (18,704 cells, n = 9), we define signatures of core, healthy, inflamed and polyp secretory cells. We reveal marked differences between the epithelial compartments of the non-polyp and polyp cellular ecosystems, identifying and validating a global reduction in cellular diversity of polyps characterized by basal cell hyperplasia, concomitant decreases in glandular cells, and phenotypic shifts in secretory cell antimicrobial expression. We detect an aberrant basal progenitor differentiation trajectory in polyps, and propose cell-intrinsic13, epigenetic14,15 and extrinsic factors11,16,17 that lock polyp basal cells into this uncommitted state. Finally, we functionally demonstrate that ex vivo cultured basal cells retain intrinsic memory of IL-4/IL-13 exposure, and test the potential for clinical blockade of the IL-4 receptor α-subunit to modify basal and secretory cell states in vivo. Overall, we find that reduced epithelial diversity stemming from functional shifts in basal cells is a key characteristic of type 2 immune-mediated barrier tissue dysfunction. Our results demonstrate that epithelial stem cells may contribute to the persistence of human disease by serving as repositories for allergic memories.

Effectiveness of antibiotic treatment in infertile patients with sterile leukocytospermia induced by tobacco use.

Our study investigated whether antibiotic therapy in infertile tobacco users with sterile leukocytospermia and a history of former sexual transmitted disease (STD) has an advantage over cessation of smoking alone. For this study, 80 male infertile smokers were divided into two subgroups. The first group numbered 40 patients treated with a two week course of doxycycline, 100 mg, twice daily, while the second group simply ceased smoking. A control group of 20 patients with chronic abacterial prostatitis (CPPS III a) were treated with the same antibiotic for two weeks. Patients from the first group exhibited significantly higher values in semen volume, total motility, and progressive motility of spermatozoa, when compared with the second group, two weeks post treatment. The latter two measures persisted during the 12 week follow up period. In both groups of patients, the correlation coefficient between the number of leukocytes and progressive motility was determined as statistically significant. However, in the control group the correlation was not statistically significant; however progressive motility, total motility, and vitality were significantly improved after a two week course of antibiotics. Our study implies that antibiotic treatment is perhaps effective in treating sterile leukocytospermia in smokers with a former STD and is a more effective treatment option in improving sperm parameters over smoking cessation alone. ABBREVIATIONS: STD: sexual transmitted disease; CPPS IIIa: chronic abacterial prostatitis; PSA: prostatic specific antigen; EPS: expressed prostatic secretion; WBC: white blood count; LUTS: lower urinary tract symptoms; PPMT: pre-massage and post-massage urine test; VAS: visual analogue scale.

The effects of postharvest application of lecithin to improve storage potential and quality of fresh goji (Lycium barbarum L.) berries.

To enhance storage life and post-storage quality of fresh goji berries, three treatments with lecithin (1, 5, 10g·L-1) and two storage times (8, 16days) were evaluated. The significant effects on the physiological and biochemical parameters were varied. 1g·L-1 lecithin showed its main effects after 8days of storage by reduction in total weight loss and decay, SSC/TA ratio (also at 16days), and chlorophyll content and with highest scores of sensory attributes (also at 16days). 5g·L-1 lecithin showed its main effects after 16days of storage: highest SSC, highest TA (also at 8days), highest TPC, only significant reduction in DPPH antioxidant activity, and highest total flavonoid content. 10g·L-1 lecithin showed its main effects after 8days of storage with highest SSC, chlorophyll content, total flavonoid, DPPH, and ABTS antioxidant activity (also at 16days), but with least scores of sensory attributes.

Discrimination of different body structure indexes of elite athletes in combat sports measured by multi frequency bioimpedance method / Discriminación de diferentes índices de estructura corporal de atletas de elite en deportes de combate medidos por el método de bioimpedancia de múltiples frecuencias

In order to achieve high results in sports, it is necessary to provide an adequate status of an athlete in according to various factors, among which the body structure is one of greater importance. The aim of this research is to define the most discriminated indicators of body structure indexes, thanks to which a specific change of physical structure can be observed according to a branch of sport and type of combat sport. Variables in the research were: body height, body mass, body mass index, free fat mass index, fat mass index, protein mass index, skeletal muscle mass index, percent of body fat, percent of skeletal muscle mass and protein fat index. The measuring of the body composition is realized by using multichannel segmental bioimpedance with InBody 720 apparatus, applied on the total of 112 male high level senior-age athlete members of different national team's member of Republic of Serbia (62 judokas, 29 Greco-Roman style wrestlers and 21 karatekas). The discriminative analysis has shown that subsamples of the athletes statistically differ in morphology on Wilks' lambda level (0.435, p = 0.000), and that following variables have the highest discrimination compared to athlete respondents in sport function: percent of skeletal mass (0.34), percent of body fat (0.28) and protein fat index (0.26), as the first isolated factor (p = 0.000) by which is explained 86.3 %, that is body weight (0.74), skeletal muscle index (0.73), protein mass index (0.72), body mass index (0.72) and free fat mass index (0.70), as the second factor (p = 0.030) by which 13.7 % variability of measured body structure space is explained. By establishing body structure models of judokas, wrestlers and karatekas for variables examined and by using modern technological method of measuring (InBody 720, 2008) we got new information that characterize specificity of the sport, which all contribute to spreading and improving already existing knowledge in the sports sciences and sport body morphology area.

Para obtener logros deportivos de alto nivel, es necesario conseguir el estatus adecuado dependiendo de varios factores, entre los cuales destaca el factor morfológico. El objetivo de este estudio fue definir los indicadores más discriminantes de la composición corporal o índices morfológicos, por lo cual se puedan monitorear los cambios específicos en la estructura del cuerpo en relación con la rama del deporte y el tipo de deportes de combate. Las variables del estudio fueron: altura del cuerpo, masa corporal, índice de masa corporal, índice de masa grasa, índice de proteína masa, índice de masa del músculo esquelético, porcentaje de grasa corporal, porcentaje de masa del músculo esquelético y el índice grasa proteína. La medición de la composición corporal fue realizada utilizando la bioimpedancia segmentaria multicanal con Inbod café 720 sobre una muestra de 112 deportistas de sexo masculino de categoría sénior, miembros nacionales seleccionados de la República de Serbia (62 practicantes de judo, 29 practicantes de lucha grecorromana y 21 practicantes de karate). El análisis discriminativo demostó que las submuestras de los atletas en general difieren significativamente en la morfología a nivel de lambda de Wilks ­ 0.435, (p = 0.000), y que las siguientes variables tienen la mayor discriminación en relación con la prueba de los atletas en la función del deporte: porcentaje de la masa esquelética (0.34), porcentaje de grasa corporal (0,28) y el índice de grasa proteína (0.26), como el primer factor aislado (p = 0.000), lo que explica 86,3 %, respectivamente la masa corporal (0.74), el índice de músculo esquelético (0,73), el índice de proteína de masa (0,72), índice de masa corporal (0,72), e índice de masa libre de grasa (0,70), como el segundo factor (p = 0,030), lo que explica 13,7 % de las mediciones espaciales de variabilidad. Al definir los módulos morfológicos de los practicantes de judo, karate y lucha grecorromana para las variables investigadas y usando el método tecnológico de medida más nuevo (InBody 720), hemos obtenido nuevas informaciones que caracterizan las especificidades de los deportes, lo que contribuye a la ampliación y el desarrollo de los conocimientos anteriores sobre dicho asunto.

Complications of Laparoscopic Cholecystectomy: Our Experience from a Retrospective Analysis.

AIM: The aim of this study was to evaluate the intraoperative and postoperative complications of laparoscopic cholecystectomy, as well as the frequency of conversions. MATERIAL AND METHODS: Medical records of 740 patients who had laparoscopic cholecystectomy were analysed retrospectively. We evaluated patients for the presence of potential risk factors that could predict the development of complications such as age, gender, body mass index, white blood cell count and C-reactive protein (CRP), gallbladder ultrasonographic findings, and pathohistological analysis of removed gallbladders. The correlation between these risk factors was also analysed. RESULTS: There were 97 (13.1%) intraoperative complications (IOC). Iatrogenic perforations of a gallbladder were the most common complication - 39 patients (5.27%). Among the postoperative complications (POC), the most common ones were bleeding from abdominal cavity 27 (3.64%), biliary duct leaks 14 (1.89%), and infection of the surgical wound 7 patients (0.94%). There were 29 conversions (3.91%). The presence of more than one complication was more common in males (OR = 2.95, CI 95%, 1.42-4.23, p < 0.001). An especially high incidence of complications was noted in patients with elevated white blood cell count (OR = 3.98, CI 95% 1.68-16.92, p < 0.01), and CRP (OR = 2.42, CI 95% 1.23-12.54, p < 0.01). The increased incidence of complications was noted in patients with ultrasonographic finding of gallbladder empyema and increased thickness of the gallbladder wall > 3 mm (OR = 4.63, CI 95% 1.56-17.33, p < 0.001), as well as in patients with acute cholecystitis that was confirmed by pathohistological analysis (OR = 1.75, CI 95% 2.39-16.46, p < 0.001). CONCLUSION: Adopting laparoscopic cholecystectomy as a new technique for treatment of cholelithiasis, introduced a new spectrum of complications. Major biliary and vascular complications are life threatening, while minor complications cause patient discomfort and prolongation of the hospital stay. It is important recognising IOC complications during the surgery so they are taken care of in a timely manner during the surgical intervention. Conversion should not be considered a complication.