Humans ; Lung Transplantation/adverse effects* ; Risk Factors

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.
Male ; Female ; Humans ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Adult ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Immune Checkpoint Inhibitors ; Gastrectomy/methods* ; Esophagogastric Junction/pathology* ; Laparoscopy ; Immunotherapy ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome

Female ; Humans ; Ovarian Neoplasms/surgery* ; Sex Cord-Gonadal Stromal Tumors/surgery* ; Myxoma/surgery*

Objective: To investigate the value of inflammation,coagulation and nutrition markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection(PJI). Methods: A retrospective study was conducted on 70 patients who undertook prosthesis removal and antibiotic-loaded bone cement spacer implantation due to PJI from June 2016 to October 2020 in the Department of Orthopedics,Henan Provincial People's Hospital. There were 28 males and 42 females,aged (65.5±11.9) years (range: 37 to 88 years). Patients were divided into two groups as the successful group and the failed group depended on whether reinfection occurred after prosthesis removal and antibiotic-loaded bone cement spacer implantation at the last follow up. Patient demographics,laboratory values (C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),ESR and CRP ratio (ESR/CRP),white blood cell count(WBC),platelet count(PLT),hemoglobin(HB),total lymphocyte count(TLC),albumin、fibrinogen(FIB),CRP and albumin ratio (CAR),prognostic nutritional index(PNI)),and reinfection rates were assessed. Comparison between groups was conducted by the independent sample t test or χ²test. Receiver operating characteristic (ROC) curve was plotted,and the area under the curve (AUC),optimal diagnostic threshold,sensitivity,and specificity were analyzed to predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation. Results: All patients were followed up for at least two years,and the follow-up time was (38.4±15.2) months (range: 24 to 66 months). Fifteen patients suffered failure after prosthesis removal and antibiotic-loaded bone cement spacer implantation,while the other 55 patients succeeded. The overall failure rate of prosthesis removal and antibiotic-loaded bone cement spacer implantation in PJI treatment was 21.4%. Level of preoperative CRP ((35.9±16.2)mg/L),PLT ((280.0±104.0)×10⁹/L) and CAR (1.3±0.8) in successful group were lower than CRP ((71.7±47.3)mg/L),PLT ((364.7±119.3)×10⁹/L) and CAR (2.5±2.0) in failed group (all P<0.05).Whereas,level of preoperative ESR/CRP (3.3±3.1), Albumin ((35.3±5.2)g/L) and PNI (43.6±6.2) in successful group were higher than ESR/CRP (1.6±1.4),Albumin ((31.3±4.8)g/L) and PNI (39.2±15.1) in failed group (all P<0.05). AUC of ROC curve,optimal threshold value,sensitivity and specificity of CRP,ESR/CRP, PLT, Albumin,CAR and PNI for the predicting failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation were 0.776(95%CI:0.660 to 0.867),35.4 mg/L,86.7%,67.3%;0.725(95%CI:0.605 to 0.825),1.0,60.0%,78.2%;0.713(95%CI:0.593 to 0.815),253,93.3%,47.3%;0.721(95%CI:0.601 to 0.822),35.7,93.3%,49.1%;0.772(95%CI:0.656 to 0.863),1.1,86.7%,67.3%;0.706(95%CI:0.585 to 0.809),45.7,100%,41.8% respectively. Conclusion: In patients with PJI,CRP>35.4,ESR/CRP≤1.0 and CAR>1.1 could predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Objective: To obtain experience and generate suggestions for reducing average hospital stays, optimizing perioperative management of patients with gastric cancer and improving utilization of medical resources by analyzing the factors influencing super-long hospital stays in patients undergoing radical gastrectomy in the age of enhanced recovery after surgery (ERAS). Methods: This was a case-control study. Inclusion criteria: (1) pathologically diagnosed gastric adenocarcinoma; (2) radical surgery for gastric cancer; and (3) complete clinicopathologic data. Exclusion criteria: (1) history of upper abdominal surgery; (2) presence of distant metastasis of gastric cancer or other ongoing neoplastic diseases; (3) concurrent chemoradiotherapy; and (4) preoperative gastric cancer-related complications such as obstruction or perforation. The study cohort comprised 285 eligible patients with hospital stays of ≥30 days (super-long hospital stay group). Using propensity score matching in a 1:1 ratio, age, sex, medical insurance, pTNM stage, and extent of surgical resection as matching factors, 285 patients with hospital stays of < 30 days during the same period were selected as the control group (non-long hospital stay group). The primary endpoint was relationship between pre-, intra-, and post-operative characteristics and super-long hospital stays. Clavien-Dindo grade was used to classify complications. Results: Univariate analysis showed that number of comorbidities, number of preoperative consultations, preoperative consultation, inter-departmental transference, operation time, open surgery, blood loss, intensive care unit time, presence of surgical or non-surgical complications, Clavien-Dindo grade of postoperative complications, and reoperation were associated with super-long hospital stays (all P<0.05). Inter-departmental transference (OR=4.876, 95% CI: 1.500-16.731, P<0.001), preoperative consultation time ≥ 3 d (OR=1.758, 95%CI: 1.036-2.733, P=0.034), postoperative surgery-related complications (OR = 6.618, 95%CI: 2.141-20.459, P=0.01), and higher grade of complications (Clavien-Dindo Grade I: OR = 7.176, 95%CI: 1.785-28.884, P<0.001; Clavien-Dindo Grade II: OR = 18.984, 95%CI: 6.286-57.312, P<0.001; Clavien-Dindo Grade III-IV: OR=7.546, 95%CI:1.495-37.952, P=0.014) were independent risk factors for super-long hospital stays. Conclusion: Optimizing preoperative management, enhancing perioperative management, and surgical quality control can reduce the risk of prolonging average hospital stay.
Humans ; Case-Control Studies ; Retrospective Studies ; Length of Stay ; Stomach Neoplasms/pathology* ; Enhanced Recovery After Surgery ; Gastrectomy/adverse effects* ; Postoperative Complications/etiology*

Humans ; Diverticulum, Colon ; Fecal Impaction ; Hydrodynamics

COVID-19 ; Humans ; Living Donors ; Lung ; Lung Transplantation ; Pandemics ; SARS-CoV-2 ; Tissue Donors ; Treatment Outcome

Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions. Newly-generated neurons in the subventricular zone migrate to the olfactory bulb (OB) and determine olfactory discrimination, but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear. Our previous study indicated the potential of APPL2 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system. In the present study, we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells (NSCs) and an in vivo animal model-APPL2 transgenic (Tg) mice. In the in vitro study, we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis. In the in vivo study, APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system, including the corpus callosum, OB, and rostral migratory stream. Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice. Furthermore, we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors. In conclusion, APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.

Background/Aims: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. Methods: We prospectively recruited patients with Child’s A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment. Results: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed. Conclusions GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.