[Clinical characteristics of immune checkpoint inhibitor-related type 1 diabetes mellitus].

The clinical data of ten patients with immune checkpoint inhibitor-related type 1 diabetes mellitus were enrolled in the Second Xiangya Hospital of Central South University from January 2020 to October 2022 including 9 males and 1 female, with an average age of (57±8) years. There were 7 cases of fulminant type 1 diabetes and 3 cases of acute type 1 diabetes. Among the 10 patients, there were 5 cases of lung cancer, 2 cases of esophageal cancer, 1 case of gastric carcinom, 1 case of renal cell carcinoma, and 1 case of nasopharyngeal cancer. The drugs used in 10 patients were all programmed cell death receptor 1 (PD-1) inhibitors, including 5 cases of pembrolizumab, 3 cases of sintilimab, 1 case of tanezumab, and 1 case of toripalimab. Among them, 8 patients had diabetic ketoacidosis (DKA), 1 patient had ketosis, and 1 case had no ketosis at onset; 9 patients were negative for diabetes-related antibodies, and 1 patient was positive. All the 10 patients were successfully treated and depended on insulin therapy. Immune checkpoint inhibitors can cause type 1 diabetes, including fulminant type 1 diabetes, which mostly begins with DKA, requiring early identification and aggressive insulin therapy.

[Identification of rare variants in exons of NLRC4 gene in patients with type 1 diabetes and their impact on gene function].

Objective: To identify rare variants in exon and exon-intron boundary of containing NLR family CARD domain protein 4 (NLRC4) in type 1 diabetes (T1DM) patients, and to explore their effects on gene function. Methods: A total of 508 T1DM patients and 527 healthy controls in the Department of Metabolic Endocrinology, Second Xiangya Hospital of Central South University from August 2017 to September 2020 were selected. The case group included 264 males and 244 females, and the age [M (Q1, Q3)] was [27 (11, 43)] years. The control group included 290 males and 237 females, and their ageï¼»M（Q1，Q3）］was [47 (36, 60)] years old. Identification of rare variants in exons of NLRC4 gene in T1DM patients and healthy controls was performed and verified by next-generation sequencing and sanger sequencing. The NLRC4 gene wild-type and mutant plasmids were constructed and transfected into 293T cells. Western blot (WB) was used to detect the expression of NLRC4 protein and cleavage products of pro-cysteinyl aspartate specific proteinase(procaspase-1). Cycloheximide (CHX) was added to 293T cells transfected with wild-type or mutant NLRC4 plasmid to detect the degradation of NLRC4 protein. The localization of NLRC4 protein was detected by immunofluorescence, and the concentration of IL-1ß in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Results: The sequencing results showed that 4 patients and 2 healthy controls had a heterozygous variant c.208C>T in exon 3 of the NLRC4 gene. Two patient had a heterozygous variant c.1564T>C in exon 4, and 1 patients had c.1219G>C in exon 4. These three variants might be pathogenic variants in T1DM. In 293T cells transfected with NLRC4 wild-type and c.208C>T、c.1564T>Cc.1219G>C mutant plasmids, the expression level, degradation rate, localization of NLRC4 protein and the content of cleavage products of procaspase-1 did not change significantly. However, the concentration of IL-1ß secreted by 293T cells transfected with c.1219G>C and c.208C>T plasmid [M(Q1, Q3)] was 15.25 (12.98, 17.52) and 15.44 (13.81, 17.07) ng/L, respectively, which was lower than 18.70 (16.59, 20.81) ng/L of 293T cells transfected wild-type plasmid (P=0.020, 0.010). Conclusions: NLRC4 gene rare variants c.208C>T, c.1564T>C and c.1219G>C may not change the protein expression, degradation and localization, but c.208C>T and c.1219G>C may inhibit the secretion of IL-1ß. This result suggests that NLRC4 rare variants may have an impact on gene function.

[Identification of HLA class â ¡ susceptible alleles and genotypes in latent autoimmune diabetes in adults].

Objective: To identify human leukocyte antigen (HLA)-DRB1, DQA1 and DQB1 susceptible alleles and genotypes in latent autoimmune diabetes in adults (LADA) patients of Chinese Han nationality. Methods: All subjects including 652 LADA patients and 1 181 healthy controls from 1999 to 2015 in Han nationality region of Hunan province were genotyped with high resolution at HLA-DRB1, DQA1 and DQB1 locus by PCR-sequence based typing (PCR-SBT). Frequencies of genotypes between patients and controls were compared by chi square test. Results: The DQA1 susceptible allele was DQA1*03 (OR=1.23, P(c)=0.028); the DQB1 susceptible alleles were DQB1*0201 (OR=2.24, P(c)<0.001), DQB1*0303 (OR=1.30, P(c)=0.030), DQB1*0304 (OR=10.23, P(c)=0.004) and DQB1*0401(OR=1.94, P(c)<0.001); and the DRB1 susceptible alleles were DRB1*0301 (OR=2.10, P(c)<0.001), DRB1*0405(OR=1.89, P(c)<0.001) and DRB1*0901(OR=1.36, P(c)=0.008), respectively in Chinese Han nationality LADA patients. The HLA-Ⅱ susceptible genotypes were DQA1*03/05 (OR=1.81, P(c)=0.007), DQB1*0201/0201(OR=5.74, P(c)<0.001), DQB1*0201/0303 (OR=2.58, P(c)=0.010), DRB1*0301/0901(OR=3.43, P(c)=0.028) and DRB1*0901/0901 (OR=1.82, P(c)=0.021), respectively in LADA patients. DQB1*0201 and DRB1*0301 were shared susceptible alleles for Chinese Han and Caucasian LADA patients, while DQA1*03, DQB1*0303, DQB1*0304, DQB1*0401, DRB1*0405 and DRB1*0901 were specific susceptible alleles for Chinese Han LADA patients. Interestingly, the DQB1*0303 allele was susceptible in Chinese while protective in Caucasian (OR: 1.30 vs 0.29). Conclusion: Susceptible alleles are DQA1*03, DQB1*0201, DQB1*0303, DQB1*0304, DQB1*0401, DRB1*0301, DRB1*0405 and DRB1*0901, and susceptible genotypes are DQA1*03/05, DQB1*0201/0201, DQB1*0201/0303, DRB1*0301/0901 and DRB1*0901/0901 in Chinese LADA patients.

[Surgical site infection after abdominal surgery in China: a multicenter cross-sectional study].

Objective: Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery. Methods: A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery. Results: A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ(2)=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ(2)=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions: The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.

[Risk factors for surgical site infection after emergency abdominal surgery: a multicenter cross-sectional study in China].

Objective: Surgical site infection (SSI) is the most common infectious complication after emergency abdominal surgery (EAS). To a large extent, most SSI can be prevented, but there are few relevant studies in China. This study mainly investigated the current situation of SSI occurrence after EAS in China, and further explored risk factors for SSI occurrence. Methods: Multi-center cross-sectional study was conducted. Clinical data of patients undergoing EAS in 33 hospitals across China between May 1, 2019 and June 7, 2019 were prospectively collected, including perioperative data and microbial culture results from infected incisions. The primary outcome was the incidence of SSI after EAS, while the secondary outcomes were postoperative hospital stay, ICU occupancy rate, length of ICU stay, hospitalization cost, and mortality within postoperative 30 days. Univariate and multivariate logistic regression models were used to analyze the risk factors of SSI after EAS. Results: A total of 660 EAS patients aged (47.9±18.3) years were enrolled in this study, including 56.5% of males (373/660). Forty-nine (7.4%) patients developed postoperative SSI. The main pathogen of SSI was Escherichia coli [culture positive rate was 32.7% (16/49)]. As compared to patients without SSI, those with SSI were more likely to be older (median 56 years vs. 46 years, U=19 973.5, P<0.001), male [71.4% (35/49) vs. 56.1% (343/611), χ(2)=4.334, P=0.037] and diabetes [14.3% (7/49) vs. 5.1% (31/611), χ(2)=5.498, P=0.015]; with-lower preoperative hemoglobin (median: 122.0 g/L vs. 143.5 g/L, U=11 471.5, P=0.006) and albumin (median: 35.5 g/L vs. 40.8 g/L, U=9452.0, P<0.001), with higher blood glucose (median: 6.9 mmol/L vs. 6.0 mmol/L, U=17 754.5, P<0.001); with intestinal obstruction [32.7% (16/49) vs. 9.2% (56/611), χ(2)=25.749, P<0.001], with ASA score 3-4 [42.9% (21/49) vs. 13.9% (85/611), χ(2)=25.563, P<0.001] and with high surgical risk [49.0% (24/49) vs. 7.0% (43/611), χ(2)=105.301, P<0.001]. The main operative procedure resulting in SSI was laparotomy [81.6%(40/49) vs. 35.7%(218/611), χ(2)=40.232, P<0.001]. Patients with SSI experienced significantly longer operation time (median: 150 minutes vs. 75 minutes, U=25 183.5, P<0.001). In terms of clinical outcome, higher ICU occupancy rate [51.0% (25/49) vs. 19.5% (119/611), χ(2)=26.461, P<0.001], more hospitalization costs (median: 44 000 yuan vs. 15 000 yuan, U=24 660.0, P<0.001), longer postoperative hospital stay (median: 10 days vs. 5 days, U=23 100.0, P<0.001) and longer ICU occupancy time (median: 0 days vs. 0 days, U=19 541.5, P<0.001) were found in the SSI group. Multivariate logistic regression analysis showed that the elderly (OR=3.253, 95% CI: 1.178-8.985, P=0.023), colorectal surgery (OR=9.156, 95% CI: 3.655-22.937, P<0.001) and longer operation time (OR=15.912, 95% CI:6.858-36.916, P<0.001) were independent risk factors of SSI, while the laparoscopic surgery (OR=0.288, 95% CI: 0.119-0.694, P=0.006) was an independent protective factor for SSI. Conclusions: For patients undergoing EAS, attention should be paid to middle-aged and elderly patients and those of colorectal surgery. Laparoscopic surgery should be adopted when feasible and the operation time should be minimized, so as to reduce the incidence of SSI and to reduce the burden on patients and medical institutions.

[A multicenter cross-sectional study on chronic critical illness and surgery-related chronic critical illness in China].

Objective: To understand the prevalence, diagnosis and treatment of chronic critical illness (CCI) in China. Methods: The clinical data of 472 adult patients admitted to ICU in 53 hospitals, including basic information, disease-related data, nutrition program, etc., were collected on May 10, 2019, by means of multi-center cross-sectional study. If surgical intervention was needed or the occurrence of the disease was directly related to the surgery, ICU patients were regarded as surgical ICU cases (n=211). In this study, the diagnostic criteria for CCI were: (1) admission to ICU >14 days;(2) combined with persistent organ dysfunction. The prevalence,distribution and treatment of CCI and surgery-related CCI were recorded and analyzed. The Mann-Whitney U test, chi-square test or Fisher exact test were used for comparative analysis. Results: Among the 472 ICU patients from 53 hospitals, 326 were male (69.1%) and 146 were female (30.9%). The prevalence of CCI was 30.7% (145/472). Among 211 surgery-related ICU patients, 57 developed CCI with a prevalence of 27.0%. As compared to non-CCI patients, higher APACHE II score [median (IQR) 13.5 (10.0, 18.3) vs. 11.0 (7.0, 16.0), U=2970.000, P=0.007], higher Charlson comorbidity index [median (IQR) 4.0 (2.0, 7.0) vs. 3.0 (1.0, 5.0), U= 3570.000, P=0.036] and higher ratio of breath dysfunction [68.4% (39/57) vs. 48.1% (74/154), χ(2)=6.939, P=0.008] and renal dysfunction [42.1% (24/57) vs. 18.2% (28/154), χ(2)=12.821, P<0.001] were found in surgery-related CCI patients. While SOFA score, Glasgow coma score and other visceral function were not significantly different between surgery-related CCI and non-CCI patients (all P>0.05). NUTRIC score showed that surgery-related CCI patients had higher nutritional risk [43.9% (25/57) vs. 26.6%(41/154), U=5.750, P=0.016] and higher ratio of mechanical ventilation [66.7% (38/57) vs. 52.3% (79/154), χ(2)=3.977, P=0.046] than non-CCI patients. On the survey day, the daily caloric requirements of 50.2% (106/211) of surgery-related ICU patients were calculated according to the standard adult caloric intake index (104.6 to 125.5 kJ·kg(-1)·d(-1), 1 kJ=0.239 kcal), and the daily caloric requirements of 46.4% (98/211) of patients were calculated by physicians according to the severity of the patient's condition. 60.2% (127/211) of nutritional support therapy was enteral nutrition (including a combination of enteral and parenteral nutrition), while the remaining patients received parenteral nutrition (24.6%, 52/211), simple glucose infusion (9.0%, 19/211), or oral diet (6.2%, 13/211). The target calorie of CCI group was 104.6 (87.9, 125.5) kJ·kg(-1)·d(-1), and the actual calorie intake accounted for 0.98 (0.80, 1.00) of the target calory. In the non-CCI group, the target calorie was 104.6 (87.9, 125.5) kJ·kg(-1)·d(-1), and the actual calorie consumed accounted for 0.91 (0.66, 1.00) of the target calorie. There was no statistically significant difference between two groups (P=0.248, P=0.150). Conclusion: The prevalence of CCI and surgery-related CCI in ICU is high, along with severe complications, respiratory and renal dysfunction and mechanical ventilation. Surgical patients admitted to ICU are at high nutritional risk, and active and correct nutritional support is essential for such patients.

[Investigation of treatment and analysis of prognostic risk on enterocutaneous fistula in China: a multicenter prospective study].

Objective: To investigate the diagnosis and treatment for enterocutaneous fistula (ECF) in China, and to explore the prognostic factors of ECF. Methods: A multi-center cross-sectional study was conducted based on the Registration System of Chinese Gastrointestinal Fistula and Intra-Abdominal Infections to collect the clinical data of ECF patients from 54 medical centers in 22 provinces/municipalities from January 1, 2018 to December 31, 2018. The clinical data included patient gender, age, length of hospital stay, intensive care unit (ICU) admission, underlying diseases, primary diseases, direct causes of ECF, location and type of ECF, complications, treatment and outcomes. All medical records were carefully filled in by the attending physicians, and then re-examined by more than two specialists. The diagnosis of ECF was based on the clinical manifestations, laboratory/imaging findings and intraoperative exploration. Results: A total of 1521 patients with ECF were enrolled, including 1099 males and 422 females, with a median age of 55 years. The top three primary diseases of ECF were malignant tumors in 626 cases (41.2%, including 540 gastrointestinal tumors, accounting for 86.3% of malignant tumors), gastrointestinal ulcers and perforations in 202 cases (13.3%), and trauma in 157 cases (10.3%). The direct causes of ECF were mainly surgical operation in 1194 cases (78.5%), followed by trauma in 156 (10.3%), spontaneous fistula due to Crohn's disease in 92 (6.0%), radiation intestinal injury in 41 (2.7%), severe pancreatitis in 20 (1.3%), endoscopic treatment in 13 (0.9%) and 5 cases (0.3%) of unknown reasons. All the patients were divided into three groups: 1350 cases (88.7%) with simple ECF, 150 (9.9%) with multiple ECF, and 21 (1.4%) with combined internal fistula. Among the patients with simple ECF, 438 cases (28.8%) were jejuno-ileal fistula, 313 (20.6%) colon fistula, 170 (11.2%) rectal fistula, 111 (7.3%) duodenal fistula, 76 (5.0%) ileocecal fistula, 65 (4.3%) ileocolic anastomotic fistula, 55 (3.6%) duodenal stump fistula, 36 (2.4%) gastrointestinal anastomotic fistula, 36 (2.4%) esophagogastric/esophagojejunal anastomotic fistula, 29 (1.9%) gastric fistula and 21 (1.4%) cholangiopancreatiointestinal. Among all the simple ECF patients, 991 were tubular fistula and 359 were labial fistula. A total of 1146 patients finished the treatment, of whom 1061 (92.6%) were healed (586 by surgery and 475 self-healing) and 85 (7.4%) died. A total of 1043 patients (91.0%) received nutritional support therapy, and 77 (6.7%) received fistuloclysis. Infectious source control procedures were applied to 1042 patients, including 711 (62.0%) with active lavage and drainage and 331 (28.9%) with passive drainage. Among them, 841 patients (73.4%) underwent minimally invasive procedures of infectious source control (replacement of drainage tube through sinus tract, puncture drainage, etc.), 201 (17.5%) underwent laparotomy drainage, while 104 (9.1%) did not undergo any drainage measures. A total of 610 patients (53.2%) received definitive operation, 24 patients died within postoperative 30-day with mortality of 3.9% (24/610), 69 (11.3%) developed surgical site infection (SSI), and 24 (3.9%) had a relapse of fistula. The highest cure rate was achieved in ileocecal fistula (100%), followed by rectal fistula (96.2%, 128/133) and duodenal stump fistula (95.7%,44/46). The highest mortality was found in combined internal fistula (3/12) and no death in ileocecal fistula. Univariate prognostic analysis showed that primary diseases as Crohn's disease (χ(2)=6.570, P=0.010) and appendicitis/appendiceal abscess (P=0.012), intestinal fistula combining with internal fistula (χ(2)=5.460, P=0.019), multiple ECF (χ(2)=7.135, P=0.008), esophagogastric / esophagojejunal anastomotic fistula (χ(2)=9.501, P=0.002), ECF at ileocecal junction (P=0.012), non-drainage/passive drainage before the diagnosis of intestinal fistula (χ(2)=9.688, P=0.008), non-drainage/passive drainage after the diagnosis of intestinal fistula (χ(2)=9.711, P=0.008), complicating with multiple organ dysfunction syndrome (MODS) (χ(2)=179.699, P<0.001), sepsis (χ(2)=211.851, P<0.001), hemorrhage (χ(2)=85.300, P<0.001), pulmonary infection (χ(2)=60.096, P<0.001), catheter-associated infection (χ(2)=10.617, P=0.001) and malnutrition (χ(2)=21.199, P<0.001) were associated with mortality. Multivariate prognostic analysis cofirmed that sepsis (OR=7.103, 95%CI:3.694-13.657, P<0.001), complicating with MODS (OR=5.018, 95%CI:2.170-11.604, P<0.001), and hemorrhage (OR=4.703, 95%CI: 2.300-9.618, P<0.001) were independent risk factors of the death for ECF patients. Meanwhile, active lavage and drainage after the definite ECF diagnosis was the protective factor (OR=0.223, 95%CI: 0.067-0.745, P=0.015). Conclusions: The overall mortality of ECF is still high. Surgical operation is the most common cause of ECF. Complications e.g. sepsis, MODS, hemorrhage, and catheter-associated infection, are the main causes of death. Active lavage and drainage is important to improve the prognosis of ECF.

WITHDRAWN: Adjuvant portal vein chemotherapy improves the efficacy of hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus.

This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause.

[Classification of urogenital tract infection in 518 cases and drug sensitivity analysis].

In 518 cases with urogenital tract infection detected with mycoplasma identification susceptibility testing reagent box, 308 cases (59.4%) were infected by ureaplasma urealyticum (Uu), 21 cases (4.1%) were infected by mycoplasma hominis (Mh), and 189 cases (36.5%) were infected by both Uu and Mh. Drug sensitivity to the macrolides (erythromycin, roxithromycin, josamycin, azithromycin), the tetracyclines (doxycycline, minocin), and the quinolines (ofloxacin, ciprofloxacin) were detected at the same time. The results showed that the sensitivity to various antibiotics in Uu infection was different from that in Mh infection. Macrolides were more sensitive for Uu infection, and quinolines were more sensitive for Mh infection, while the mixed infection of Mh and Uu had resistance to most antibiotics.