CRS Group Research Articles

Hyperglycemia and type 2 diabetes mellitus associate with postoperative recurrence in chronic rhinosinusitis patients.

To investigate the associations between fasting blood glucose (FBG) and type 2 diabetes mellitus (T2DM) and the risk of postoperative CRS recurrence. A retrospective cohort study was conducted on clinical data of CRS patients who underwent surgery at our center between February 2019 and March 2022 and were followed up until June 2023. All CRS patients were categorized into two subgroups based on the presence of T2DM and postoperative recurrence. The Kaplan-Meier survival curves and binary logistic regression analyses were performed to examine the associations between FBG, T2DM, and the risk of postoperative CRS recurrence. 1163 CRS patients were enrolled, including 134 in the T2DM group and 276 in the recurrent group. The recurrence rate in the T2DM group was significantly higher than that in the non-T2DM group (P < 0.05). T2DM prevalence and FBG levels were higher in the recurrent CRS group than in the non-recurrent CRS group (P < 0.05). The Kaplan-Meier survival curves and unadjusted and adjusted logistic regression models showed that T2DM was an independent risk factor for postoperative CRS recurrence (P < 0.05). Moreover, multivariate logistic regression analysis suggested that FBG, CRS duration, and allergic rhinitis were associated with the risk of postoperative CRS recurrence (P < 0.05). Elevated FBG levels and accompanying T2DM were associated with an increased risk of postoperative CRS recurrence, which was independent of traditional risk factors. CRS duration and accompanying allergic rhinitis were also proven to be potential risk factors for postoperative CRS recurrence.

Delay in Time to Adjuvant Chemotherapy and its Impact on Oncological Outcomes in Patients Undergoing Optimal Cytoreductive Surgery for Advanced Ovarian Cancer: Analysis of 1480 Cases From the Indian HIPEC Registry.

The impact of delay in initiation of adjuvant chemotherapy following optimal CRS in different settings of treatment for advanced ovarian cancer needs to be studied with special reference to CRS HIPEC. The 1480 advanced EOC patients underwent optimal CRS, followed by adjuvant chemotheraphy, with or without intraperitoneal (IP) chemotherapy in Normothermic or Hyperthermic form. Interval between the day of surgery and start of adjuvant chemotherapy and its impact on outcome was analyzed. CRS, CRS with IP or HIPEC was done in 400, 480, and 600 patients respectively. Median interval of starting adjuvant chemotherapy was 32 days CRS group, 34 days CRS + IP group and 41 days CRS + HIPEC group. Delay in chemotherapy impacted on recurrence free survival (RFS) in CRS + IV group (36 vs. 17 months: p = 0.02) and some impact in CRS + IP group (38 vs. 28 months; P 0.78) and no impact on CRS + HIPEC group (35 vs. 32 months; p = 0.17). Delay in starting adjuvant chemotherapy adversely affects RFS in patients undergoing optimal CRS alone. However, the delay didn't have an impact in the CRS + HIPEC group. Well-designed clinical studies are required to evaluate the impact of single dose of HIPEC.

Insufficient Diagnostic Value of Serum Galactomannan and (1,3)-β-D-Glucan in Paranasal Sinus Fungus Balls

Background and Objectives: The serum galactomannan test (GM test) and the (1,3)-β-D-glucan test (G test) are utilized in diagnosing invasive fungal sinusitis. However, their effectiveness in detecting paranasal sinus fungus balls (FBs) has not been established. This study aimed to explore their diagnostic value in patients with FBs.Methods: We retrospectively reviewed the medical records of 105 patients (42 with FBs and 63 with chronic rhinosinusitis [CRS]) who underwent serum GM and G tests between June 2020 and May 2021. Olfactory test results and demographics were also analyzed.Results: There were 42 FB patients (10 men, 32 women) and 63 CRS patients (27 men, 36 women). The positivity rates for serum GM (7.1% in the FB group vs. 3.2% in the CRS group, p=0.640) and G test (9.5% in the FB group vs. 11.1% in the CRS group, p=0.482) did not differ significantly between groups. The sensitivities of the GM and G tests were 7.1% and 9.5%, respectively, and their specificities were 96.8% and 88.9%, respectively. The positive predictive values were 60.0% for the GM test and 36.3% for the G test, and the negative predictive values were 61.0% for the GM test and 59.6% for the G test.Conclusion: Serum GM and G tests demonstrated low sensitivity and high specificity, indicating limited effectiveness in differentiating between patients with FBs and those with CRS. Histological examination remains the gold standard for the definitive diagnosis of FBs.

Clinical analysis of the correlation between the expression of soluble B cell maturation antigen and the efficacy of chimeric antigen receptor T cell targeting B cell maturation antigen in patients with multiple myeloma

Objective: The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) . Methods: This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared. Results: ①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD (P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM (R(2)=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion: sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.

Long‐term outcomes and survival analysis of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei at a newly established peritoneal malignancy centre in Japan

AbstractBackgroundCytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is established in the management of pseudomyxoma peritonei (PMP), selected cases of peritoneal mesothelioma, and resectable colorectal or ovarian peritoneal metastases in Western countries. However, the efficacy and feasibility of these techniques are not well established in the Asian population, and little has been reported on long‐term survival outcomes for surgically resected PMP patients.Materials and MethodsRetrospective analysis of a prospective database of short‐ and longer‐term outcomes of consecutive patients who underwent CRS and HIPEC for PMP in a newly established peritoneal malignancy unit in Japan between 2010 and 2016.ResultsA total of 105 patients underwent CRS and HIPEC and 57 maximal tumor debulking (MTD) for pseudomyxoma peritonei. In the CRS group, the primary tumor was appendiceal in 94 patients (90%) followed by ovarian and colorectal. Major postoperative complications occurred in 22/105 patients (21%) with one in‐hospital mortality (0.9%). The 5‐year overall and disease‐free survival rates for the CRS group were 74.2% and 50.1%, respectively. Multivariate analysis revealed unfavorable histology to be the significant predictor of reduced overall and disease‐free survival. Completeness of cytoreduction, CA19‐9, and CA125 were also associated with disease‐free survival.ConclusionsThis is the first report on long‐term outcomes and survival analysis of CRS and HIPEC for PMP in the Asian population. CRS and HIPEC can be conducted with reasonable safety and favorable survival in a new center. Complete tumor removal and histological type are the strongest prognostic factors for both overall and disease‐free survival.

The Impact of the Nasal Mucosal Flap on Tissue Remodeling After Sinus Bone Drilling in Rabbit Models.

Frontal sinus surgery remained a challenge of restenosis or obliteration of the drainage pathway caused by the scarring and neo-osteogenesis after mucosal stripping and bone drill-out. The pedicled or free nasal mucosal flap is typically used to repair the exposed bone surface to avoid or reduce recurrence. This study aimed to explore the histopathological mechanism of mucosal flaps repairing bare bone after mucosal resection and bone drill-out in the rabbit model. Thirty New Zealand white rabbits were used. Sixteen rabbits were selected as the experimental group, and Staphylococcus aureus was used to establish the CRS model (CRS group). Fourteen healthy rabbits were allocated to the control group (NCRS group). Each group was divided into two subgroups with or without mucosal flap repair (CRS-FLAP, CRS-NFLAP, NCRS-FLAP, and NCRS-NFLAP, respectively). The bony anterior and lateral walls of the maxillary sinus of each rabbit were abraded by the drill. The bare bone was then covered with a flap in FLAP subgroups. Bone remodeling and mucosal morphological changes were observed and compared by histopathological hematoxylin and eosin and Masson staining. In the CRS-NFLAP subgroup, the regenerated epithelium lacked typical structure, accompanied by numerous inflammatory cell infiltration and collagen deposition. Conversely, the inflammatory reaction was mild in the CRS-FLAP subgroup, and there was less collagen deposition. The restored mucosal structure was like the normal mucosa. The epithelium in the NCRS-NFLAP subgroup was partially exfoliated, with few cilia, goblet cells, and glandular structures. Compared with the NCRS-NFLAP subgroup, the CRS-NFLAP subgroup showed significant bone remodeling with enhanced activity of osteoblast and osteoclast cells. Pedicled mucosal flap repair could significantly reduce local mucosal and bone remodeling in a rabbit model of CRS.

Factors Impacting Follow-Up Care in Allergic Fungal Rhinosinusitis.

The purpose of this study was to analyze barriers to medical care and follow-up in patients with allergic fungal rhinosinusitis (AFRS). Cross-sectional questionnaire-based study with retrospective chart review. Tertiary Medical Center. Subjects with AFRS and chronic rhinosinusitis with nasal polyps (CRSwNP) were prospectively recruited for completion of the Barriers to Care Questionnaire (BCQ) and formal chart review. Fifty-nine AFRS and 51 CRSwNP patients participated. AFRS patients were more likely to be lost to follow-up within 6 months of surgery (35.6% vs17.7%, P = 0.04) and no-show at least 1 appointment (20.3% vs5.9%, P = 0.03) compared to CRSwNP patients. Men with AFRS were more likely to have only a single follow-up visit (37.0% vs3.1%, P < 0.001) and be lost to follow-up (66.7% vs9.4%, P < 0.001) than women. There were no significant differences in the BCQ between groups; however, rate of questionnaire completion was lower in the AFRS group than the CRS group (62.7% vs 80.4%, P = 0.042). AFRS patients who did not complete the BCQ were more likely to be male (63.6% vs35.1%, P = 0.034), lost to follow-up (77.3% vs10.8%, P < 0.0001), and have a single follow-up visit (40.9% vs5.4%, P < 0.0001). Younger age was associated with increased likelihood of having a single follow-up visit (odds ratio 1.143, 95% CI 1.022-1.276). Young, male AFRS patients are more frequently lost to follow-up after surgery and less likely to complete questionnaires assessing barriers to care. Further investigation is needed to assess barriers to follow-up in these at-risk groups.

Effects of Glutamine, Curcumin and Fish Bioactive Peptides Alone or in Combination on Intestinal Permeability in a Chronic-Restraint Stress Model.

Irritable bowel syndrome (IBS), a multifactorial intestinal disorder, is often associated with a disruption in intestinal permeability as well as an increased expression of pro-inflammatory markers. The aim of this study was to first test the impact of treatment with glutamine (Gln), a food supplement containing natural curcumin extracts and polyunsaturated n-3 fatty acids (Cur); bioactive peptides from a fish protein hydrolysate (Ga); and a probiotic mixture containing Bacillus coagulans, Lactobacillus acidophilus, Lactobacillus gasseri and Lactobacillus helveticus. These compounds were tested alone on a stress-based IBS model, the chronic-restraint stress model (CRS). The combination of Gln, Cur and Ga (GCG) was also tested. Eight-week-old C57Bl/6 male mice were exposed to restraint stress for two hours every day for four days and received different compounds every day one week before and during the CRS procedure. Plasma corticosterone levels were measured as a marker of stress, and colonic permeability was evaluated ex vivo in Ussing chambers. Changes in the gene expression of tight junction proteins (occludin, claudin-1 and ZO 1) and inflammatory cytokines (IL1β, TNFα, CXCL1 and IL10) were assessed using RT-qPCR. The CRS model led to an increase in plasma corticosterone and an increase in colonic permeability compared with unstressed animals. No change in plasma corticosterone concentrations was observed in response to CRS with the different treatments (Gln, Cur, Ga or GCG). Stressed animals treated with Gln, Cur and Ga alone and in combination showed a decrease in colonic permeability when compared to the CRS group, while the probiotic mixture resulted in an opposite response. The Ga treatment induced an increase in the expression of the anti-inflammatory cytokine IL-10, and the GCG treatment was able to decrease the expression of CXCL1, suggesting the synergistic effect of the combined mixture. In conclusion, this study demonstrated that a combined administration of glutamine, a food supplement containing curcumin and polyunsaturated n-3 fatty acids, and bioactive peptides from a fish hydrolysate was able to reduce colonic hyperpermeability and reduce the inflammatory marker CXCL1 in a stress-based model of IBS and could be of interest to patients suffering from IBS.

Study to Determine Role of Fungus in Cases of Chronic Rhinosinusitis with or without Nasal Polyps in Indian Population

Introduction Chronic rhinosinusitis (CRS) with or without nasal polyps is a significant public health burden worldwide and owing to its multifactorial etiology, it is often encountered across various medical and surgical specialities. Role of fungus in etiology of CRS has been debated for decades altogether and there is plethora of researches on cellular, molecular and biochemical aspects of fungal presence in nasal cavity and paranasal sinuses and how it affects. Although, there is denial at large on fungal effects on development of CRS, but the question, that whether concomitant and demonstrable presence of fungus in cases of CRS aggravates classic symptoms and signs, largely remains unanswered. Material and Methods This cohort study includes 121 subjects, which were divided in CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) on basis of rigid nasal endoscopic findings. Severity of disease symptoms, among these groups was corelated with Lund – Mackay (LM) symptom scores and extent of disease with LM endoscopic staging scores and LM radiology scores. Histopathology samples for demonstrating presence of fungus were taken and cohort was further subdivided into Fungi positive CRS and Fungi negative CRS, and, LM scores were compared. Results In fungi positive CRS group, mean LM symptoms score was 7.09 with standard deviation (SD) ±1.07; mean LM endoscopy score was 6.64 with SD ±1.94 and LM radiological score was 14.58 with SD ±2.96. In Fungi negative group, mean LM symptoms score was 3.58 with SD ±1.30; mean LM endoscopy score was 4.47 with SD ±1.57 and LM radiological score was 12.20 with SD ±2.98. Conclusion Results of this study were statistically significant that fungi positive group was found to have more severe symptoms and larger extent of disease as compared to fungi negative group which indicate that fungal presence may have a role in escalation of symptoms, signs and radiological scores and it may aggravate pre-existing CRS.

Hyperthermic intraperitoneal chemotherapy following up-front cytoreductive surgery versus cytoreductive surgery alone for isolated synchronous colorectal peritoneal metastases: A retrospective, observational study.

To date, the value of hyperthermic intraperitoneal chemotherapy (HIPEC) following up-front resection for isolated synchronous colorectal peritoneal metastases seems controversial. This retrospective cohort study was conducted from September 1, 2012, to September 1, 2019, at a tertiary medical center in China. Patients with isolated synchronous colorectal peritoneal metastases were included in CRS plus HIPEC group or CRS alone group based on the treatment history. Overall survival and relapse-free survival were estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. 78 patients with isolated synchronous colorectal peritoneal metastases were identified among 396 patients with synchronous colorectal peritoneal metastases. 43 were in the cytoreductive surgery plus HIPEC group and 35 were in the cytoreductive surgery alone group. Among them, 61 patients had relapse-free survival data. The median peritoneal cancer index was 4 in all patients. After a median follow-up of 46.0 months, 5-year overall survival was 66.8% and the median relapse-free survival was 36.0 (95% CI, 6.8-65.1) months in the CRS plus HIPEC group. 5-year overall survival was 31.2% and the median relapse-free survival was 12.0 (95% CI, 9.0-15.0) months in the CRS alone group. Cox regression analyses showed that HIPEC was the independent prognostic factor for overall survival (P = 0.004) and relapse-free survival (P = 0.049). Findings of the present study suggest that HIPEC following up-front CRS could improve overall survival and relapse-free survival in patients with isolated synchronous colorectal peritoneal metastases.

Pharmaco-mechanical catheter-directed thrombolysis versus recanalization and stenting for post thrombotic syndrome after lower limb deep vein thrombosis: a comparative study.

Endovenous interventional procedures can be used in addition to therapeutic anticoagulation to treat deep vein thrombosis in selected patients with proximal vein involvement (vena cava, iliac and/or common femoral). The aim of this study was to compare venous patency and the post-thrombotic syndrome (PTS) in patients treated with pharmaco-mechanical catheter-directed thrombolysis (PMT) versus recanalization-stenting for PTS after a proximal lower limb deep vein thrombosis. Between January 2014 and December 2020, this retrospective and monocentric study included patients with very symptomatic acute iliofemoral deep vein thrombosis treated with PMT within 21 days after diagnosis (PMT group) and patients with PTS caused by chronic venous obstruction treated with recanalization and stenting (CRS group). A total of 116 patients were included (26 PMT, 90 CRS). The rate of primary patency was 81.8% (18/22 patients) in the PMT group and 78.4% (69/88) in the CRS group (P>0.99). The rate of venous patency at the last follow-up was 76.9% (20/26) in the PMT group and 82.2% (74/90) in the CRS group (P=0.57). The median number of stents was 2 (range, 0-5) in the PMT group and 3 (range, 0-7) in the CRS group (P<0.001). The median stent length was 150 mm (range, 60-390 mm) and 280 mm (range, 120-820 mm), respectively (P<0.001). The median last Villalta score was 2 (range, 0-10) in the PMT group and 2 (range, 0-21) in the CRS group (P=0.55). The rate of venous claudication at the last follow-up was 19.0% (4/21) in the PMT group and 12.0% (10/83) in the CRS group (P=0.47). In this study, there was no difference in venous patency and in the rate and severity of PTS between the PMT and CRS groups. The number of stent and their length were significantly lower in the PMT group compared with the CRS group.

Effects of substituting soybean meal with corn on immune function and gene expression of gut TLR4 pathway of growing goats.

BackgroundProtein malnutrition remains a severe problem in ruminant production and can increase susceptibility to infection, especially during the growth stage. This study aimed to explore substituting soybean meal with corn on activation of the TLR pathway and potential impact on immune response bias towards Type 1 or Type 2 using growing female goats as experimental animals.MethodsTwenty-four Xiangdong black goats (initial BW = 19.83 ± 0.53 kg, about 8 ± 0.3 months old) were selected and randomly divided into the corn-soybean meal basal diet group (CON, 10.77% protein) and replacing soybean meal with 100% of corn group (CRS, 5.52% protein). EDTA whole blood and serum samples were collected prior to slaughter for determinations of blood cell counts, anti-inflammatory cytokines and antibodies. The duodenum, jejunum, ileum and colon tissues were collected after formal trial to study the effect of CRS diet on the expression of TLR4 pathway.ResultsOur results showed CRS diet did not induce a significant change in immune function, as evidenced by the observations that white blood cell (WBC), neutrophil (Neu), lymphocyte (Lym), monocyte (Mon), eosinophil (Eos), interleukin-4 (IL-4), IL-5, IL-13, immunoglobin G (IgG), IgA, and IgM levels in serum were similar between the two groups. RT-PCR results showed the expression of tumor necrosis factor-α (TNF-α) (P < 0.01) and interferon-β (IFN-β) (P < 0.01) were up-regulated in the colon of goats in the CRS group. No differences in the expression of myeloid differentiation factor 88 (MyD88) adaptor-like protein (TIRAP), IL-1 receptor–associated kinase 1 (IRAK1), TNF receptor related factor 6 (TRAF6), NF-kappa B (NF-κB), mitogen-activated protein kinase 1 (MAPK1) or activator protein-1 (AP-1) in the TLR4/MyD88 dependent pathway were observed between the two groups for any of the tested tissue. However, the expression of NF-κB activator (TANK) binding kinase 1 (TBK1) in TLR4/MyD88 independent pathway was up-regulated in the duodenum and colon (P < 0.01), and the expression of interferon regulatory factor-3 (IRF3) was up-regulated (P < 0.01) in colon.ConclusionsOur results suggested that the CRS diet failed to induce a significant change in innate immunity and adaptive immunity in growing goats. However, the up-regulated TBK1 and IRF3 in the colon from the CRS goats suggests that the CRS diet may induce the expression of Th1-type proinflammatory cytokines and inflammatory response through a TLR4-MyD88-independent pathway, and the colon may be the easiest targeted section in the intestinal tract.

Bacterial biofilm in adults with ENT pathology

Introduction. Chronic rhinosinusitis, a very common inflammatory condition, is a main public health issue affecting the quality of life. Furthermore, some patients do not respond to either medical or surgical intervention, which could be explained by the presence of the bacterial biofilm in the rhinosinusal zone. Objectives. The aim of this study is to evaluate the influence of endoscopic sinus surgery on olfactory impairment caused by chronic sinusitis with and without nasal polyps (CRSNP and CRS), by testing the olfactory function and potential dysfunction before and after endoscopic sinus surgery. Another objective is to find a connection between the percentage of coverage with bacterial biofilm of the nasal mucosa from patients with CRSNP and CRS and to evidence the fountain of infection role of the bacterial biofilm, while demonstrating that antibiotic therapy is not efficient once the bacterial biofilm is formed in the nasal sinuses. Materials and methods. We investigated 123 patients with CRSNP and CRS, which underwent functional endoscopic sinus surgery (FESS). The olfactory function was tested pre and post FESS. We also analyzed and compared the scores of endoscopic images of Lund-Kennedy and CT staging scale of LundMackey for the two study groups. The degree of olfactory rehabilitation in patients with CRSNP and CRS was evaluated performing smell diskettes test. The presence of bacterial biofilm on the surface of the nasal mucosa extracted during FESS from patients with CRSNP and CRS was examined with the electronic microscope and the percentage of coverage with bacterial biofilm was measured with Carnoy software. Results. Bacterial biofilm was present in a higher percentage in patients with CRS vs. CRSNP. By comparing the level of olfactory function, significant improvement was found after FESS intervention in both study groups. Postoperatively, Lund-Kennedy scores decrease significantly for the whole group (Z = -9.66 at p &lt; 0.001, d Cohen = 4.40), indicating the major role of surgery in the treatment of CRS. The decrease in Lund-Kennedy score values is also significant for each group. In the case of subjects diagnosed with CRS, the mean values decrease from 6.57 (preoperative) to 0.90 (postoperative), respectively Z = -6.779 to p &lt; 0.001. In the case of subjects diagnosed with CRSNP, the mean values decrease from 9.03 (preoperative) to 1.44 (postoperative), Z = -6.927 at p &lt; 0.001. Out of the total number of patients included in the study, 59 patients tested positive with the Prick test for dust and mites and more than half of the patients with positive allergy test were from the lot diagnosed with CRSNP. Conclusions. FESS plays an important role in the improvement of olfactory function in patients with CRS. Bacterial biofilm was present in both study groups but in higher percentage in the CRS group and was found in lower percentage in the group with positive allergy tests. The CRSNP group presented a higher positive result regarding the allergy Prick test and a lower percentage of coverage with bacterial biofilm of the nasal mucosa. In conclusion, chronic rhinosinusitis with or without nasal polyps that is refractary to antibiotic therapy should be directed to the ENT department in order to receive surgical therapy in order to improve olfactory function.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy vs. cytoreductive surgery alone for intrahepatic cholangiocarcinoma with peritoneal metastases: A retrospective cohort study

BackgroundCytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has survival benefits in patients with intraperitoneal malignant lesions, but there is no study specific to intrahepatic cholangiocarcinoma (ICC). PurposeTo compare the prognosis of patients with advanced ICC undergoing CRS + HIPEC compared with CRS alone. MethodsThis study was a retrospective cohort study of patients with advanced ICC treated at the Shanghai Eastern Hepatobiliary Surgery Hospital between 01/2014 and 12/2018. The patients were divided into either CRS + HIPEC or CRS group based on the treatment they received. Overall survival (OS), complications, hospital stay, biochemical indicators, tumor markers, and number of HIPEC were examined. ResultsThere were 51 and 61 patients in the CRS + HIPEC and CRS groups, respectively. There were no differences between the groups regarding preoperative CA19-9 levels (421 ± 381 vs. 523 ± 543 U/mL, P = 0.208). The hospital stay was longer in the CRS + HIPEC group (22.2 ± 10.0 vs. 18.6 ± 7.6 days, P = 0.033). The occurrence of overall complications was similar in the two groups (37.2% vs. 34.4%, P = 0.756). The postoperative CA19-9 levels were lower in the CRS + HIPEC group compared with the CRS group (196 ± 320 vs. 337 ± 396 U/mL, P = 0.044). The median OS was longer in the CRS + HIPEC group than in the CRS group (25.53 vs. 11.17 months, P < 0.001). Compared with the CRS group, the CRS + HIPEC group showed a higher occurrence of leukopenia (7.8% vs. 0, P = 0.040) but a lower occurrence of total bilirubin elevation (15.7% vs. 37.7%, P = 0.032). ConclusionCRS + HIPEC could be a treatment option for patients with advanced ICC, with improved OS and similar complications and adverse events compared with CRS alone.

The expression of Notch pathway in nasal polyps and its correlation with the decreased Treg percentage and eosinophil infiltration

Objective: To investigate the correlation between Notch pathway expression in nasal polyps and Treg percentage and Eos infiltration. Methods: Patients with chronic sinusitis and simple nasal septum deviation who received nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-Sen University between November 2012 and August 2018 were selected and enrolled in CRS group and control group respectively. Nasal mucosa tissues were collected from 30 CRSsNP patients (14 males and 16 females aged from 18 to 63), 58 CRSwNP patients (38 males and 20 females aged from 18 to 65) and 29 patients (19 males and 10 females aged from 20 to 57), who underwent nasal endoscopic surgery for correction of simple nasal septum deviation. Hematoxylin-eosin(HE) staining was used to observe the infiltration of eosinophilic granulocytes in the tissues and to classify chronic sinusitis with polyps (CRSwNP) into eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP)and non-eosinophilic chronic rhinosinusitis with nasal polyps (Eos-CRSwNP). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Notch pathway receptors (Notch-l, 2, 3, 4) and their ligands (Jagded-l, Jagded-2, Delta-l, Delta-3and Delta-4) in the nasal mucosa of each group, as well as the expression of Th2 cytokines (IL-4, IL-5, IL-13), eosinophilic cationic protein (ECP)and the key transcription factor Foxp3 in Treg cells. Finally, flow cytometry was used to detect CD4+CD25+Foxp3+ Treg cells in nasal mucosa of each group. Results: Compared with controls, the expression of Th2 cytokines (IL-4, IL-5, IL-13) in CRSsNP and non-Eos-CRSwNP patients was the highest in Eos-CRSwNP (F=16.930,9.197,9.116, all P<0.05). Foxp3 had the lowest expression in Eos-CRSwNP patients and was lower than non-Eos-CRSwNP patients (F=2.780,P<0.05), and was negatively correlated with ECP (r=-0.326,P<0.05). Compared with controls, Eos-CRSwNP patients in CRSsNP patients and non-Eos-CRSwNP patients exhibited a significantly lower frequency of CD4+CD25+Foxp3+Treg cells (F=13.140, all P<0.01). The expression of Notch-l and Jagged-l in Eos-CRSwNP was significantly higher than that of the controls, CRSsNP patients and non-Eos-CRSwNP patients (F=5.953/F=6.380, P<0.05). In the nasal polyp group, the expression of Notch-l and Jagged-l showed significantly negative correlation with Foxp3 (r=-0.611/-0.346, all P<0.05), and positive correlation with Th2 cytokines (IL-4, IL-5, IL-13) and ECP, respectively (r=0.781/0.459,0.621/0.601,0.605/0.490,0.464/0.668, all P<0.05). There was no significant difference in the expression of receptor and ligand of the other Notch pathway among the groups. Conclusion: Abnormal activation of Notch-l/Jagged-l pathway may be involved in decreasing Treg ratio in Eos-CRSwNP, thereby promoting Th2 inflammatory response and Eosinophil infiltration.

Calorie restriction and synbiotics effect on quality of life and edema reduction in breast cancer-related lymphedema, a clinical trial

BackgroundLittle evidence exists regarding the clinical value of synbiotics in the management of post-treatment complications of breast cancer especially breast cancer-related lymphedema (BCRL). This study aimed to investigate the effects of synbiotic supplementation along with calorie restriction on quality of life and edema volume in patients with BCRL. MethodsThis randomized, placebo-controlled, clinical trial was conducted on 135 overweight and obese women with BCRL aged 18–65 years old. Participants were randomly allocated to receive a calorie-restricted diet plus 109 CFU synbiotic supplement (CRS group; n = 45) or placebo (CRP group; n = 45), daily for 10 weeks. Also, a control group (n = 45) with no intervention was included in the trial. All of the participants received Complete Decongestive Therapy for lymphedema treatment. The quality of life score, edema volume and body mass index (BMI) were measured at baseline and end of the trial. ResultsA total of 121 subjects completed the trial. CRS group showed a significant decrease in the total quality of life score (P = 0.004), and it’s psychosocial (P = 0.022) and functional (P = 0.002) domain scores, as well as edema volume (P = 0.002) and BMI (P < 0.001) in comparison to the control. However, there were no significant differences in changes in trial outcomes between the CRS and CRP groups. ConclusionSynbiotic supplementation along with a low-calorie diet was effective in quality of life, edema volume, and BMI improvement; mostly due to low-calorie diet. It seems that adding a dietitian consultation on the lymphedema management strategy may provide a better result in lymphedema control.

Progressive Tibial Bearing Sagittal Plane Conformity in Cruciate-Retaining Total Knee Arthroplasty

BackgroundWe hypothesized that when the posterior cruciate ligament (PCL) is found deficient at total knee arthroplasty (TKA), using an anterior-stabilized (AS) tibial insert would provide similar function and survivorship when compared to using a more traditional cruciate-retaining (CR) bearing when the (PCL) is balanced. MethodsA total of 1731 TKAs were performed using the same TKA design. Of them, 868 TKAs had a standard CR insert implanted (CR-S), 480 TKAs used a lipped CR insert (CR-L), and 383 TKAs used an AS insert. If the PCL was considered nonfunctional or absent, an AS bearing was placed. When the PCL was balanced, a CR-S or CR-L bearing was used. Follow-up was performed using the Knee Society scoring system. Kaplan-Meier survivorship was used with failure defined as aseptic loosening. ResultsAt final follow-up, there were no significant differences in knee flexion, pain, function, or stair scores. Walking scores were significantly lower in the AS group. Posterior instability was higher in the CR-S group, whereas the manipulation rate was highest in the CR-L group (1.7%, 1.3%, and 0% for CR-L, CR-S, and AS groups, respectively). Kaplan-Meier survivorship at 5 years demonstrated no significant difference between the 3 groups (99% 100%, and 99% for CR-S, CR-L, and AS groups, respectively). ConclusionUsing an AS insert provided similar function and 5-year survivorship as compared to using a CR-S and CR-L tibial insert when the PCL was balanced. Using an ultracongruent AS dished tibial component appears to be a reasonable option when the PCL is completely released or found deficient at operation.

Individualized positive end-expiratory pressure setting in patients with severe acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation.

Patients with acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation benefit from higher positive end-expiratory pressure combined with conventional ventilation during the early extracorporeal membrane oxygenation period. The role of incremental positive end-expiratory pressure titration in patients with severe acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation remains unclear. This study aimed to determine the preferred method for setting positive end-expiratory pressure in patients with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation support. We retrospectively reviewed all subjects supported with veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from 2009 to 2019 in the intensive care units in Tianjin Third Central Hospital. Subjects were divided into two groups according to the positive end-expiratory pressure titration method used: P-V curve (quasi-static pressure-volume curve-guided positive end-expiratory pressure setting) group or Crs (respiratory system compliance-guided positive end-expiratory pressure setting) group. Forty-three subjects were included in the clinical outcome analysis: 20 in the P-V curve group and 23 in the Crs group. Initial positive end-expiratory pressure levels during veno-venous extracorporeal membrane oxygenation were similar in both groups. Incidence rates of barotrauma and hemodynamic events were significantly lower in the Crs group (all p < 0.05). Mechanical ventilation duration, intensive care unit length of stay, and hospital length of stay were significantly shorter in the Crs group than the P-V curve group (all p < 0.05). Subjects in the Crs group showed non-significant improvements in the duration of extracorporeal membrane oxygenation support and 28-day mortality (p > 0.05). Respiratory system compliance-guided positive end-expiratory pressure setting may lead to more optimal clinical outcomes for patients with severe acute respiratory distress syndrome supported by veno-venous extracorporeal membrane oxygenation. Moreover, the operation is simple, safe, and convenient in clinical practice.

P0563THE SHORT AND LONG-TERM EFFECTS OF HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY ON RENAL FUNCTION IN PLATINUM-SENSITIVE RECURRENT OVARIAN CANCER

Abstract Background and Aims Cytoreductive surgery (CRS) with platinum based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) represents a valid therapeutic approach in the treatment of ovarian cancer patients with peritoneal spread (vanDriel NEJM). Nevertheless, cisplatin nephrotoxicity represents one limitation to the diffusion of HIPEC in clinical practice. To date, few studies evaluated the nephrotoxicity of hyperthermic intraperitoneal cisplatin and the risk of acute kidney injury (AKI) in patients treated with HIPEC. The aim of our study is to evaluate short- and long-term changes in serum creatinine (SCr) levels in a cohort of patients with a first relapse of platinum-sensitive ovarian cancer, receiving CRS plus or minus HIPEC. Method We compared a cohort of patients with a first relapse of platinum-sensitive ovarian cancer, receiving CRS plus/minus HIPEC in a period from January 2013 to October 2018. The HIPEC technique required the perfusion of the abdominal cavity with a 4 L/m2 of a heated saline solution containing cisplatin 75 mg/m2. We assessed the estimated glomerular filtration rate (eGFR), using the CKD-EPI formula, and SCr from the preoperative value, at 24, 48, 72 hours, 7 days and the last SCr value available on the electronic record, at least 3 months after the procedure. We analyzed the effect of HIPEC treatment on SCr values over time and we used logistic regression models to investigate the effect of HIPEC treatment on clinical outcomes. No patient in the HIPEC group had kidney protective treatment with thiosulphate. Results Our analyses included complete data of 110 patients treated in our Institution from January 2013 to October 2018. The two groups had significant differences in baseline SCr (p-value = 0.002), with lower average values in the CRS+HIPEC group (mean 0.68, standard deviation [SD] 0.14 mg/dL) compared to the CRS group (mean 0.76, SD 0.13 mg/dL). The baseline eGFR was significantly higher in the CRS+HIPEC group (mean 95, SD 16 mL/min/1.73 m2) than in the CRS group (mean 88, SD 14 mL/min/1.73 m2) (p-value = 0.014) and three patients in each group had chronic kidney disease (CKD) before surgery. SCr values in the HIPEC group were significantly higher at post-operative day #7 (1.22 ± 1.10 mg/dL vs 0.69 ± 0.16 mg/dL; p-value &amp;lt;0.001) and the differences remained during follow-up at least three months after randomization (0.96 ± 0.55 vs 0.69 ± 0.19 mg/dL; p-value &amp;lt;0.001). Seventeen patients (31%) developed Acute Kidney Injury (AKI), according to the KDIGO Guidelines, in the first week after CRS+HIPEC versus seven patients (13%) after CRS alone. No patients who developed AKI post-HIPEC needed renal replacement treatment, although 5 (9%) had AKI stage III and 7 (13%) stage II. The CRS+HIPEC group had a significantly higher risk of developing AKI [OR: 3.48 (2.30-5.27)] compared with the CRS group (p-value &amp;lt;0.001). There were no statistically significant differences between the two groups with regard to risk of complications other than AKI. Conclusion To our knowledge, our study represents the first investigation on short- and long-term changes in SCr and on the risk of AKI in patients with a first relapse of platinum-sensitive ovarian cancer, treated with CRS and HIPEC. There is a strong correlation between the intraperitoneal cisplatin at elevated temperatures and the rise of SCr over the time. However, this event was no reversible and influenced following treatments in only eight women.

Comparative analysis of the R&D investment performance of Korean local governments

This study examines Korea's research and development (R&D) investment performance at the local government level using slack-based model data envelopment analysis (SBM-DEA). The SBM methodology, which has replaced the traditional DEA model, is expected to provide more reliable empirical results for R&D investment performance. We confirm the statistical reliability of our results by conducting bootstrapping. The average score of Korea's R&D investment performance is 67.7%, implying that there is a 32.3% potential for efficiency improvement. Among the 16 local governments examined, Seoul, Gwangju, Daegu, and Gangwon show better performance with an average value higher than 0.8. We decomposed R&D investment efficiency into pure R&D investment technical efficiency and scale efficiency and derived implications regarding the input scales. We also reported benchmark information from trend-setting local governments that indicate ideal input mixes for fast-following local governments. Since no local government was found to be in the CRS group, we suggest that all local governments should transform their R&D investment input mix toward upscaling or downsizing.