Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

OBJECTIVE: To compare the effectiveness and advantages of the double reverse traction reduction versus open reduction internal fixation for treating complex tibial plateau fractures. METHODS: A clinical data of 25 patients with Schatzker type Ⅴ or Ⅵ tibial plateau fractures, who met the selection criteria and were admitted between January 2019 and January 2023, was retrospectively analyzed. Thirteen patients underwent double reverse traction reduction and internal fixation (double reverse traction group), while 12 patients underwent open reduction and internal fixation (traditional open group). There was no significant difference in the baseline data (age, gender, injury mechanism, Schatzker classification, interval between injury and operation) between the two groups ( P>0.05). The effectiveness were evaluated and compared between the two groups, included operation time, intraoperative blood loss, incision length, hospital stay, full weight-bearing time, complications, fracture healing, Rasmussen radiological score (reduction quality), knee Hospital for Special Surgery (HSS) score, and knee flexion/extension range of motion. RESULTS: The double reverse traction group demonstrated significantly superior outcomes in operation time, intraoperative blood loss, hospital stay, incision length, and time to full weight-bearing ( P<0.05). Two patients in traditional open group developed incisional complications, while the double reverse traction group had no complication. There was no significant difference in the incidence of complication between the two groups ( P>0.05). All patients were followed up 24-36 months (mean, 30 months), with no significant difference in follow-up duration between groups ( P>0.05). Fractures healed in both groups with no significant difference in healing time ( P>0.05). At 6 months after operation, Rasmussen radiological scores and grading showed no significant difference between the two groups ( P>0.05); the double reverse traction group had significantly higher HSS scores compared to the traditional open group ( P<0.05). At 12 months after operation, knee flexion/extension range of motion were significantly greater in the double reverse traction group than in the traditional open group ( P<0.05). CONCLUSION Double reverse traction reduction offers advantages over traditional open reduction, including shorter operation time, reduced blood loss, minimized soft tissue trauma, and improved joint functional recovery. It is a safe and reliable method for complex tibial plateau fractures.
Humans ; Tibial Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Male ; Female ; Traction/methods* ; Retrospective Studies ; Middle Aged ; Adult ; Open Fracture Reduction/methods* ; Treatment Outcome ; Range of Motion, Articular ; Fracture Healing ; Operative Time ; Length of Stay ; Blood Loss, Surgical ; Aged ; Tibial Plateau Fractures

BACKGROUND:Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism.The present study aimed to establish a new scoring system to predict mechanical ventilation(MV)for botulism patients. METHODS:A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022.Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system.The area under the receiver operating characteristic(ROC)curve was calculated. RESULTS:A total of 153 patients with botulism(66 males and 87 females,with an average age of 43 years)were included.Of these,49 patients(32.0%)required MV,including 21(13.7%)with invasive ventilation and 28(18.3%)with non-invasive ventilation.Multivariate analysis revealed that botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement were independent risk factors for MV.These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system.Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization([botulinum toxin type A:1],[pneumonia:2],[incubation period≤1 day:2],[hypoxia<90%:2],[severity of muscle involvement:grade II,3;grade III,7;grade IV,11]).The scoring system achieved an area under the ROC curve of 0.82(95%CI 0.75-0.89,P<0.001).At the optimal threshold of 9,the scoring system achieved a sensitivity of 83.7%and a specificity of 70.2%. CONCLUSION:Our study identified botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement as independent risk factors for MV in botulism patients.A score≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients.This scoring system needs to be validated externally before it can be applied in clinical settings.

Objective:To investigate a brucellosis outbreak caused by contact with unquarantined sheep in Chongqing, and provide reference for prevention and control of brucellosis.Methods:In accordance with the requirements of the "Technical Plan of Brucellosis Prevention and Control Project of Chongqing" and the "Working Specification for Epidemic Disposal of Human Brucellosis" (DB50/T 946-2019), a self-designed brucellosis case questionnaire (version 2021) was used to carry out case investigation and laboratory tests on cases reported by medical institutions, and the data were analyzed descriptively.Results:According to "Working Specification for Epidemic Disposal of Human Brucellosis" (DB50/T 946-2019) in Chongqing, the brucellosis outbreak that occurred in December 2021 was determined to be a cluster outbreak, with a total of two confirmed cases of brucellosis, and a incidence rate of 2/9. The reason of the outbreak was the rearing and slaughtering of unquarantined sheep.Conclusion:We should strengthen the inspection and quarantine of livestock such as cattle and sheep, crack down on informal trade of livestock, and reduce the risk of brucellosis.

Objective:To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori ( H. pylori) in Ningxia. Methods:From August 12, 2022 to March 22, 2023, 600 patients diagnosed as H. pylori-positive by 14C-urea breath test ( 14C-UBT) for the first time in People′s Hospital of Ningxia Hui Autonomous Region, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region, Zhongwei People′s Hospital, Yanchi County People′s Hospital, and Pingluo People′s Hospital were selected, and divided into empirical treatment group (hereinafter referred to as the empirical group), genetic testing group (hereinafter referred to as the genetic group), and drug sensitivity testing group (hereinafter referred to as the drug sensitivity group) by using random number table with 200 patients in each group. The empirical group did not undergo drug sensitivity testing and genetic testing, while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing, and the patients with drug-resistant were excluded, respectively. All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to compare the eradication rates of H. pylori among 3 groups. Cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER) were used for cost-effectiveness and sensitivity analysis based on the ITT. Chi-square test was used for statistical analysis. Results:There were 200, 126, and 168 patients included in the empirical group, genetic group, and drug sensitivity group in ITT analysis, and 190, 123, and 164 patients were enrolled in the 3 groups in PP analysis, respectively. The results of ITT analysis showed that the eradication rates of H. pylori in the empirical group, genetic group, and drug sensitivity group were 80.5% (161/200), 94.4% (119/126), and 95.2% (160/168), respectively. The results of PP analysis indicated that the eradication rates of H. pylori in the 3 groups were 84.7% (161/190), 96.7% (119/123), and 97.6% (160/164), respectively, and the differences were statistically significant ( χ2=25.39 and 24.93, both P<0.001). The H. pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis( χ2=12.40, 17.80, 11.42, and 17.13; all P<0.001). The cost-effectiveness analysis showed that the direct treatment cost of the empirical group, genetic group, and drug sensitivity group was 400.8, 729.2, and 779.2 yuan, respectively, and the CER was 4.98, 7.72, and 8.18 yuan/%, respectively. Compared to the empirical group, the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%, respectively. The sensitivity analysis demonstrated that, when the cost of genetic testing reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%, respectively. When the cost of drug sensitivity testing reduced or increased by 20%, the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%. When the cost of gastroscopy reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%, and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%, respectively. Conclusion:In Ningxia, if the clarithromycin bismuth-containing quadruple regimen is applied as the first H. pylori eradication regimen, in order to achieve the clinical eradication efficacy of H. pylori, and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1% increasing in the H. pylori eradication rate, then the precision treatment after clarithromycin resistance test is recommended.

A puerpera with a obstetric history of gravida 2, para 2, underwent blood typing due to the presence of agglutination reactions in her serum against all tested red blood cells. She was found to be blood type O and her RhD phenotype was identified as CcDEe through serological testing. The reaction agglutination intensity between her serum and 26 O-type blood cells from the panel was 2+. Whole genome sequencing was performed, yielding data on 4014 single nucleotide polymorphisms (SNPs) and 958 insertion/deletion (INDEL) loci across 50 genes responsible for encoding blood group systems. Among these, only a single SNP , rs72552713 was predicted to be a highly harmful variant, which is the c.376C>T variation in the ABCG2 gene encoding JR blood group antigen, leading to the premature stop codon (p.Gln126Ter). The c.376C>T variation has been named the ABCG2*01N.01 by the working party on Red Cell Immunogenetics and Blood Group Terminology of International Society of Blood Transfusion. The postpartum woman was found to have the Jr(a-) phenotype. Whole genome sequencing can accurately determine the antigens of blood group systems in some difficult specimens.

Objective:To evaluate the value of left echography (LVO) in the diagnosis of false ventricular aneurysm complicated with mural thrombus.Methods:The clinical data of 10 patients with suspected pseudoventricular aneurysm examined by thoracic echocardiography (TTE) in Wuhan Asian Heart Hospital from January 2018 to March 2024 were retrospectively analyzed. All patients underwent LVO examination to further diagnose pseudoventricular tumor and whether it was complicated with mural thrombosis. Computed tomography angiography (CTA) or cardiac magnetic resonance (CMR) examination was used as the gold standard to analyze the diagnostic value of LVO in the diagnosis of pseudoventricular tumor.Results:Among the 10 suspected pseudoventricular tumors examined by TTE, LVO detected 6 cases of left ventricular pseudoaneurysm and 1 case of right ventricular pseudoaneurysm; CTA confirmed that 6 cases of left ventricular pseudoaneurysm detected by LVO were correctly diagnosed, 1 case of right ventricular pseudoaneurysm was misdiagnosed, CMR diagnosed right ventricular diverticula, LVO diagnosis accuracy was 6/7, and 4 cases of thrombi were detected. The detection rate was 4/4. The maximum transverse diameter of the tumor body of the communicating mouth/false ventricular aneurysm was 0.46±0.04. 1 patient underwent coronary artery bypass grafting and resection of false ventricular aneurysm. 1 patient underwent coronary artery interventional stent surgery; 4 routine conservative drug treatment, follow-up observation; One case of right ventricular diverticulum did not require special treatment.Conclusions:LVO contrast agent can clearly show the tumor body and location, measure the tumor entrance and size, and show mural thrombus. It is the first choice for the identification of false ventricular tumor. The diverticula was similar to the image of false ventricular aneurysm, and the sensitivity and specificity of right ventricular wall motion were higher in CMR than in LVO.

Objective:To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency.Methods:This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively.Results:The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders.Conclusions:Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Objective:To explore the application effect of breakthrough series (BTS) quality improvement model in the prevention of catheter-related bloodstream infection in hospitalized patients with indwelling non-cuffed catheter (NCC).Methods:Using a non synchronous pre and post control study method, convenience sampling was used to select NCC patients from four hospitals in Tianjin from January to September 2022 who received conventional nursing plans as the control group, and NCC patients from February to October 2023 who received nursing plans based on the BTS quality improvement model as the observation group. Compared the incidence of NCC related bloodstream infections between two groups of patients, the implementation of key preventive measures for NCC related bloodstream infections by nursing staff, and patient satisfaction.Results:Among the 984 patients included in the control group, there were 687 males and 297 females, aged (62.43 ± 13.77) years old; among the 959 patients included in the observation group, there were 651 males and 308 females, aged (61.96 ± 13.89) years old. After applying the improved model, the incidence of NCC related bloodstream infections in the observation group was 0.12‰ (1/8 676), lower than the control group′s 0.71‰ (7/9 827), and the difference was statistically significant ( χ 2=4.37, P<0.05) ;the implementation rate of key measures for preventing NCC related bloodstream infections in the observation group was 90.00% (54/60) for catheter outlet care and 91.67% (55/60) for maximizing sterile barrier, both higher than 70.37% (38/54) and 75.93% (41/54) in the control group, with statistical significance ( χ2=7.03, 5.30, both P<0.05); the total satisfaction rate of patients in the observation group was 92.91% (891/959), which was higher than 58.64% (577/984) in the control group, and the difference was statistically significant ( χ2=15.28, P<0.05). Conclusions:The implementation of BTS quality improvement model is helpful to improve the nursing quality of patients with indwelling NCC dialysis and improve the patient outcomes.