[Arterial prophylactic occlusion technique in the application of surgery for locally advanced pancreatic cancer with arterial involvement after conversion therapy].

Objective: To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy. Methods: This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group,a 1︰2 match was performed using the propensity score matching method,and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fishier's exact test were used to compare the data between the two groups,respectively. Results: After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant (t=-3.800,P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml;U=1 026.500,P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28)in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups(P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the groups(P=0.532,P=0.927). Conclusion: The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

[Diagnosis and treatment of blunt high-grade pancreatic trauma].

The clinical data of 20 patients with blunt high-grade pancreatic trauma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of Changhai Hospital Affiliated to Naval Military Medical University from December 2003 to February 2022 were retrospectively analyzed. There were 15 males and 5 females with a median age of 39 years (range: 14-54 years). The degree of pancreatic injury was graded according to the American Association for the Surgery of Trauma (AAST) scale, including 10 cases of grade Ⅲ (50%), 8 cases of grade Ⅳ (40%), and 2 cases of grade Ⅴ (10%). Then, the strategy of diagnosis and treatment for blunt high-grade pancreatic trauma was summarized. The diagnostic rate of CT was 78.9%. Finally, 17 cases (85%) were cured and 3 cases (15%) died. Among the 10 patients with grade Ⅲ pancreatic injury, 7 cases received distal pancreatectomy and splenectomy, 1 case received distal pancreatectomy with spleen preserved, 1 case received pancreatic duct stent placement under endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous catheter drainage (PCD), and 1 case received only PCD. Among 8 cases of grade Ⅳ, 3 cases underwent Roux-en-Y pancreaticojejunostomy, 1 case received distal pancreatectomy and splenectomy, 1 case underwent distal pancreatectomy with spleen preserved, 2 cases received necrotic tissue removal+external drainage of pancreatic duct+abdominal drainage, and 1 case received exploratory laparotomy and gauze packing hemostasis. For 2 cases of grade Ⅴ, 1 underwent pylorus preserving pancreaticoduodenectomy, and the other case underwent pancreaticoduodenectomy combined with right hemicolectomy and splenectomy. Therefore, the treatment of blunt high-grade pancreatic trauma should follow the individualized treatment strategy, pay attention to the control of bleeding, extensive external drainage, appropriate debridement and resection and rational application of damage control surgery, select appropriate patients for conservative treatment, and ultimately benefit the patient.

[Diagnostic efficacy for predicting intraductal papillary mucinous neoplasms of the pancreas with high grade dysplasia or invasive carcinoma based on the surgery indications in different guidelines].

Objective: To evaluate the performance of the European Evidence-based Guidelines on Pancreatic Cystic Neoplasms (EEGPCN)(2018) and International Association of Pancreatology(IAP) Guideline(Version 2017) in predicting high grade dysplasia/invasive carcinoma-intraductal papillary mucinous neoplasm(HGD/INV-IPMN). Methods: A retrospective analysis of 363 patients,who underwent surgical resection in Changhai Hospital affiliated to Navy Medical University from January 2012 to December 2018 and were pathologically identified as (intraductal papillary mucinous neoplasm, IPMN),was performed. The patients,including 230 males and 133 females,aging (61.7±10.1) years(range:19 to 83 years). The proportion of HGD/INV-IPMN who met with the absolute indication(AI) of EEGPCN and high risk stigma(HRS) of IAP were compared. The binary Logistic regression analysis was used to find the independent risk factors of HGD/INV-IPMN.Eight combinations of risk factors derived from relative indication/worrisome feature or risk factors in this study,were made to evaluate the diagnostic efficacy. The area under curve(AUC) of receiver operating characteristics was used to evaluate the the cutoff value of risk factors(①CA19-9≥37 U/ml,②diameter of main pancreatic duct 5.0-9.9 mm,③enhancing mural nodule<5 mm,④(acute) pancreatiti,⑤acyst diameter ≥40 mm,⑤bcyst diameter ≥30 mm, ⑥thickened or enhancing cyst walls,⑦neutrophile granulocyte to lymphocyte ratio(NLR)≥2, ⑧cyst located in head, uncinate or neck,⑨carcinoembryonic antigen(CEA) ≥5 µg/L) number for predicting HGD/INV-IPMN.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value,true positive,true negative,false positive,false negative,positive likelihood ratio,negative likelihood ratio,Youden index and F1 score were calculated. Results: Ninety-two patients(49.5%) of 186 ones who met AI and 85 patients(48.3%) of 176 ones who met HRS were respectively confirmed as HGD/INV-IPMN. In those patients who were not met AI,tumor location,thickened/enhancing cyst wall,CA19-9 elevated,NLR≥2 and CEA elevated were significantly (P<0.05) correlated with HGD/INV-IPMN. And tumor location(head/uncinate/neck vs. body/tail,OR=3.284,95%CI:1.268-8.503,P=0.014),thickened/enhancement cyst wall (with vs.without,OR=2.713,95%CI:1.177-6.252,P=0.019),CA19-9(≥37 U/L vs.<37 U/L, OR=5.086,95%CI:2.05-12.62,P<0.01) and NLR(≥2 vs.<2,OR=2.380,95%CI:1.043-5.434,P=0.039) were the independent risk factors of HGD/INV-IPMN. Patients with ≥4 risk factors of 9 in combination Ⅷ(①②③④⑤b⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the moderate accuracy(71.0%),moderate sensitivity (62.0%) and moderate specificity (73.0%). Patients with ≥4 risk factors of 9 in Combination Ⅶ(①②③④⑤a⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the highest specificity(83.0%) and patients with ≥3 risk factors of 8 in combination Ⅵ(①②③④⑤b⑥⑧⑨) were diagnosed as HGD/INV-IPMN with the highest sensitivity(74.0%). The AUC for diagnosis of HGD/INV-IPMN in combination Ⅵ,Ⅶ and Ⅷ were 0.72,0.75 and 0.75,respectively. Older patients and younger patients could respectively refer to combination Ⅶ and combination Ⅵ to improve the management of IPMN. Conclusions: Patients who meet AI of EEGPCN should undertake resection, otherwise the method we explored is recommended. The method of improvement for diagnosis of HGD/INV-IPMN is relatively applicable and efficient for decision-making of surgery, especially for younger patients with decreasing of missed diagnosis and elder patients with decreasing of misdiagnosis.

[Prognostic value of important driver gene mutations in patients with radical resection of pancreatic cancer].

Objective: To examine the prognostic value of four important driver gene mutations in patients with radical resection of pancreatic cancer. Methods: The clinical data and follow-up data of pancreatic cancer patients undergoing radical pancreatectomy and targeted sequencing from January 2016 to March 2018 at Department of Hepato-Biliary-Pancreatic Surgery, Changhai Hospital were retrospectively analyzed.There were 159 males and 88 females,aged of (60.8±8.7)years(range:33-83 years) and preoperative CA19-9 of (492.4±496.6)kU/L(range: 2-1 200 kU/L). One hundred and fifty nine cases of tumors were located in the head and 88 cases in the body and tail of the pancreas. After univariate analysis of clinical pathological factors (including gender, age, preoperative CA19-9, tumor location, tumor differentiation, pathological T and N stage, Micr. perineural invasion, Micr. lympho-vascular invasion, resection margin), the variable whose P<0.1 was included in COX regression model with four important driver gene mutations to find which mutation was related to prognosis independently. The number of gene mutations and KRAS subgroups were analyzed by Kaplan-Meier curve. Results: Among 247 patients,the number of KRAS,TP53, SMAD4 and CDKN2A mutations was 212 cases(85.8%), 160 cases(64.8%), 66 cases(26.7%) and 44 cases(17.8%),respectively.KRAS mutation was correlated with the tumor differentiation and pathological T stage (χ(2)=24.570/6.690, P=0.000/0.035), TP53 mutation was correlated with the tumor differentiation and the resected margin(χ(2)=5.500/4.620, P=0.019/0.032), and CDKN2A mutation was correlated with gender(χ(2)=16.574, P=0.000).COX regression model analysis showed that only KRAS mutation was an independent risk factor for disease free survival and overall survival(HR=1.776, 95%CI: 1.079-2.923, P=0.024; HR=1.923, 95%CI: 1.016-3.639, P=0.045); KRAS(G12D) mutation was associated with shorter OS(P=0.007). Conclusion: KRAS and its subgroup KRAS(G12D) mutation can be used as a prognostic index for patients with radical resection of pancreatic cancer.

The effect of dietary protein levels on the expression of genes coding for four selected protein translation initiation factors in muscle tissue of Wujin pig.

The objective of this study was to investigate the regulatory mechanism underlying the increased muscle protein accumulation in pigs while were fed a high protein diet. The eukaryotic initiation factors (eIFs) have been reported to involve in muscle protein synthesis. We investigated the mRNA and protein expression levels of eIF2B1, 4A1, 4B and 4E in Wujin pigs fed either a high protein (HP: 18%) or a low protein (LP: 14%) diet at 30, 60 or 100 kg body weight, based on real-time PCR and western blotting analyses. Our results indicated that the expression levels of eIF2B1 mRNA and protein were increased by HP diet at all body weight. The HP diet showed higher mRNA and protein levels of eIF4B gene at 60 and 100 kg. The protein expression of eIF4E phosphorylation was increased by HP diet only at 30 kg. These data suggested that the HP diet promoted porcine muscle protein accumulation mainly by up-regulating eIF2B1, 4B and 4E rather than 4A1 expression along the growth stages.

Molecular characterization and tissue expression profile of three novel ovine genes: ATP5O, NDUFA12 and UQCRH from muscle full-length cDNA library of black-boned sheep.

Three novel ovine genes were obtained from muscle full-length cDNA library of black-boned sheep. Sequence analysis revealed that nucleotide sequences of these genes were not homologous to any of the known sheep or goat genes, but these genes have high similarity to ATP synthase subunit O (ATP5O), NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 12 (NDUFA12) and ubiquinol-cytochrome c reductase hinge protein (UQCRH) genes of other mammal animals (accession number: FJ546085, FJ546078 and FJ546083). The alignment analysis showed that the ovine ATP5O, NDUFA12 and UQCRH genes and proteins have closer genetic relationships with the ATP5O, NDUFA12 and UQCRH genes and proteins from cattle. Conserved domain prediction showed that these three genes included OSCP, NDUFA12 superfamily and UCR-hinge superfamily domains respectively. The deduced sequence of ATP5O, NDUFA12 and UQCRH protein had 213, 145 and 91 amino acid residues, with a molecular weight of approximately 23419.66, 17089.50 and 10657.75 Da and a theoretical isoelectric point of 9.90, 9.68 and 4.45. The secondary structure prediction revealed that 60% helix structure in ATP5O, 60% coils in NDUFA12 and no strand in UQCRH. One potential signal peptide structure in ATP5O protein were found. NDUFA12 and UQCRH have the extremely low possibility of signal peptides. Meanwhile, RasMol was used for visualizing the PDB files generated by Swiss-Model in cartoon or three-dimensional format. ATP5O and UQCRH protein were modeled by Swiss-Model. Tissue expression profile indicated that the ovine ATP5O, NDUFA12 and UQCRH genes could be expressed in all detected tissues including muscles, heart, liver, spleen, lung, kidney and adipose tissues, but the expression abundance of these genes were various in the different tissues. Our experiment supplied the primary foundation for further researches on these three ovine genes.

Impacts of COVID-19 on the electric vehicle industry: Evidence from China.

Electric vehicle development is critical to achieve the sustainable goals, while the hit of COVID-19 strikes the market and brings challenges to the whole industry. China, among one of the earliest regions affected by COVID-19 and takes a great part in the global electric vehicle market, is attracting growing attention on its post-pandemic trends in the electric vehicle industry. This paper provides a comprehensive analysis of COVID-19 impacts on China's electric vehicle industry from both the demand side and the supply side. Both challenges and opportunities for China's electric vehicle development are revealed with emerging trend analysis. It is found that the COVID-19 outbreak has reduced electric vehicle sales in the short-term, but may also stimulate future electric vehicle demand especially for large electric cars with better performance. Meanwhile, travel restrictions caused by COVID-19 have interrupted electric vehicle material supplies that relying on imports, accelerating domestic substitute exploitation and inventory improvement for critical parts. Additionally, massive lockdowns for controlling COVID-19 have disrupted productions and operations, which tends to expel small brands out of the competitive market, concentrating China's electric vehicle industry to the leading brands. Finally, the social distancing trend after pandemic is bringing challenges to traditional EV distribution channels with dealers, pushing automakers to develop innovative online selling channels. These impacts are likely to lead to a reformation of China's electric vehicle industry towards a more advanced and reliable future.

Molecular cloning, sequence identification and tissue expression profile of three novel sheep (Ovis aries) genes - BCKDHA, NAGA and HEXA.

The complete coding sequences of three sheep genes- BCKDHA, NAGA and HEXA were amplified using the reverse transcriptase polymerase chain reaction (RT-PCR), based on the conserved sequence information of the mouse or other mammals. The nucleotide sequences of these three genes revealed that the sheep BCKDHA gene encodes a protein of 313 amino acids which has high homology with the BCKDHA gene that encodes a protein of 447 amino acids that has high homology with the Branched chain keto acid dehydrogenase El, alpha polypeptide (BCKDHA) of five species chimpanzee (93%), human (96%), crab-eating macaque (93%), bovine (98%) and mouse (91%). The sheep NAGA gene encodes a protein of 411 amino acids that has high homology with the alpha-N-acetylgalactosaminidase (NAGA) of five species human (85%), bovine (94%), mouse (91%), rat (83%) and chicken (74%). The sheep HEXA gene encodes a protein of 529 amino acids that has high homology with the hexosaminidase A(HEXA) of five species bovine (98%), human (84%), Bornean orangután (84%), rat (80%) and mouse (81%). Finally these three novel sheep genes were assigned to GenelDs: 100145857, 100145858 and 100145856. The phylogenetic tree analysis revealed that the sheep BCKDHA, NAGA, and HEXA all have closer genetic relationships to the BCKDHA, NAGA, and HEXA of bovine. Tissue expression profile analysis was also carried out and results revealed that sheep BCKDHA, NAGA and HEXA genes were differentially expressed in tissues including muscle, heart, liver, fat, kidney, lung, small and large intestine. Our experiment is the first to establish the primary foundation for further research on these three sheep genes.

cDNA cloning and tissue expression analyses of the encoding regions for three novel porcine genes- MJD1, CDC42 and NECD.

The cDNAs for Machado-Joseph disease protein 1 homolog (MJD1), cell division control protein 42 homolog precursor(CDC42) and necdin (NECD) genes of pig were amplified using the reverse transcriptase polymerase chain reaction (RT-PCR) based on the conserved coding sequence information of the MJD1, CDC42, and NECD genes from mouse and other mammals and the referenced porcine EST sequence information. Tissue expression analysis showed the swine MJD1, CDC42, and NECD genes were obviously differentially expressed in different tissues including muscle, heart, liver, backfat, kidney, lung, small intestine, and large intestine. Our experiment established the primary foundation for further research on these three swine genes.

[Cloning, nucleotide sequence and tissue expression profile of three novel porcine genes--RHOB, RHOG and PRAF1].

The complete coding sequences of three porcine genes Rho-related GTP-binding proteins RHOB and RHOG and Prenylated Rab acceptor protein 1 (PRAF1) were amplified using the reverse transcriptase polymerase chain reaction based on the sequence information of the mouse or other mammals and referenced highly homologous pig ESTs. The nucleotide sequences of these three genes revealed that porcine RHOB gene encodes a protein of 196 amino acids that contains the conserved putative RhoA-like domain and has high homology with the RHOB precursor of human, rat and mouse (100%).The porcine RHOG gene encodes a protein of 191 amino acids that contains the conserved putative RhoG domain and has high homology with the RhoG precursor (RHOG) of human, mouse and Cricetus cricetus (98%). The porcine PRAF1 gene encodes a protein of 185 amino acids that contains the conserved putative PRA1 domain and has high homology with the PRAF1 of dog (97%), cattle (97%), human (96%), rat (95%) and mouse (95%). The tissue expression analysis indicated swine RHOB gene was moderately expressed in lung, weakly in fat, spleen, kidney, and almost not expressed in small intestine, large intestine, liver, muscle. The swine RHOG gene was over-expressed in small intestine, large intestine, liver, and muscle, moderately expressed in kidney, weakly in spleen, and almost not expressed in fat and lung. The swine PRAF1 gene was over-expressed in fat and spleen, moderately in lung and kidney, weakly in small intestine and large intestine, and almost not expressed in liver and muscle.

Cytomegalovirus infection impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine in transplant arteriosclerosis.

BACKGROUND: We hypothesized that cytomegalovirus (CMV) may contribute to the vasculopathy observed in cardiac allograft recipients by impairing the endothelial nitric oxide synthase pathway. We focused on asymmetric dimethylarginine (ADMA, the endogenous inhibitor of nitric oxide synthase) as a potential mediator of the adverse vascular effect of CMV. METHODS AND RESULTS: Heart transplant recipients manifested elevated plasma ADMA levels compared with healthy control subjects. Transplant patients with CMV DNA-positive leukocytes had higher plasma ADMA concentrations and more extensive transplant arteriopathy (TA). Human microvascular endothelial cells infected with the CMV isolates elaborated more ADMA. The increase in ADMA was temporally associated with a reduction in the activity of dimethylarginine dimethylaminohydrolase (DDAH, the enzyme that metabolizes ADMA). Infected cultures showed high levels of oxidative stress with enhanced endothelial production of superoxide anion. CONCLUSIONS: CMV infection in human heart transplant recipients is associated with higher ADMA elevation and more severe TA. CMV infection in endothelial cells increases oxidative stress, impairs DDAH activity, and increases ADMA elaboration. CMV infection may contribute to endothelial dysfunction and TA by dysregulation of the endothelial nitric oxide synthase pathway.

Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebo-controlled study.

BACKGROUND: Coronary artery disease occurs in an accelerated fashion in the donor heart after heart transplantation (TxCAD), but the cause is poorly understood. The risk of developing TxCAD is increased by cytomegalovirus (CMV) infection and decreased by use of calcium blockers. Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness, and we now propose to determine whether this therapy also prevents TxCAD. METHODS AND RESULTS: One hundred forty-nine consecutive patients (131 men and 18 women aged 48+/-13 years) were randomized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation. Immunosuppression consisted of muromonab-CD3 (OKT-3) prophylaxis and maintenance with cyclosporine, prednisone, and azathioprine. Mean follow-up time was 4.7+/-1.3 years. In a post hoc analysis of this trial designed to assess efficacy of ganciclovir for prevention of CMV disease, we compared the actuarial incidence of TxCAD, defined by annual angiography as the presence of any stenosis. Because calcium blockers have been shown to prevent TxCAD, we analyzed the results by stratifying patients according to use of calcium blockers. TxCAD could not be evaluated in 28 patients because of early death or limited follow-up. Among the evaluable patients, actuarial incidence of TxCAD at follow-up (mean, 4.7 years) in ganciclovir-treated patients (n=62) compared with placebo (n=59) was 43+/-8% versus 60+/-10% (P<0.1). By Cox multivariate analysis, independent predictors of TxCAD were donor age >40 years (relative risk, 2.7; CI, 1.3 to 5.5; P<0.01) and no ganciclovir (relative risk, 2.1; CI, 1.1 to 5.3; P=0.04). Stratification on the basis of calcium blocker use revealed differences in TxCAD incidence when ganciclovir and placebo were compared: no calcium blockers (n=53), 32+/-11% (n=28) for ganciclovir versus 62+/-16% (n=25) for placebo (P<0.03); calcium blockers (n=68), 50+/-14% (n=33) for ganciclovir versus 45+/-12% (n=35) for placebo (P=NS). CONCLUSIONS: TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.

Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings.

Annual coronary arteriograms have been obtained from all heart transplant recipients at Stanford University Medical Center since 1969. Angiographic lesions in 81 transplant patients exhibiting coronary vascular disease were classified into three categories: type A, discrete or tubular stenoses; type B, diffuse concentric narrowing; and type C, narrowed irregular vessels with occluded branches. The 81 arteriograms showing transplant coronary vascular disease were contrasted with 32 from nontransplant patients with coronary artery disease analyzed in a similar fashion. The nontransplant angiograms showed 178 lesions, all of type A (discrete or tubular) morphology, 75% of which were located in primary epicardial coronary vessels and 25% in secondary branch vessels. In the patients with transplant coronary vascular disease, 349 (76%) of 461 lesions were type A: 57% in primary vessels, 42% in secondary branches and 1.4% in tertiary branches. Of the 112 type B and C lesions (diffuse narrowing, tapering and obliteration), 25% were in primary vessels, 44% in secondary vessels and 31% in tertiary branches (p less than 0.05 for patients with transplant coronary vascular disease versus patients with nontransplant coronary artery disease). Total vessel occlusion was found in proximal or middle vessel segments in 96% and distally in 4% of patients with "ordinary" coronary artery disease versus 49% distally in patients with transplant coronary disease (p less than 0.002). In the presence of total vessel occlusion, collateral vessels were poor or absent in 92% of transplant versus 7% of nontransplant patients with coronary disease (p less than 0.002). Therefore, coronary artery disease in transplant patients represents a mixture of typical atheromatous lesions and unique transplant-related progressive distal obliterative disease that occurs without collateral vessel development.

Transplant coronary artery disease: histopathologic correlations with angiographic morphology.

Accelerated coronary artery disease is a major cause of morbidity and mortality among cardiac transplant recipients. Ten patients who died or underwent retransplantation within 2 months of coronary angiography had direct correlation of angiographic (normal discrete lesions, diffuse concentric narrowing) with histologic appearance of coronary arteries. Of the 26 angiographically normal segments, 73% showed mild to moderate fibrous intimal thickening by light microscopy. The remainder had intermediate lesions or atheromatous plaques. Discrete stenoses usually corresponded to lipid-rich intermediate or atheromatous disease. In contrast, angiographically diffuse, concentrically narrowed lesions usually were areas of severe fibrous intimal thickening. Fresh or organizing thrombus was most often associated with discrete lesions and accounted for all complete occlusions. Histologic and angiographic comparisons of the degree of luminal narrowing showed generally good correlation for high grade stenoses. Lesions graded as having less than 25% diameter narrowing were often underestimated angiographically as compared with histologic determinations. Transplant coronary artery disease has a heterogeneous histologic and angiographic appearance, with angiographic underestimation of disease in some patients.

Early development of accelerated graft coronary artery disease: risk factors and course.

OBJECTIVES: This study assessed the time of first appearance of angiographic graft coronary artery disease in relation to clinical and laboratory variables and clinical events in heart transplant recipients. BACKGROUND: Graft coronary artery disease is the main factor limiting long-term survival after heart transplantation, and it is important to understand its natural history. METHODS: One hundred thirty-nine consecutive patients who developed angiographic coronary artery disease after heart transplantation were classified according to early (< or = 2 years) versus late (> 2 years) posttransplantation initial detection of coronary artery disease. These subgroups were analyzed for differences in clinical and laboratory demographics, incidence of progression to ischemic events and incidence of antecedent cytomegalovirus infection. RESULTS: The early-onset group (64 patients) had more rapid progression to ischemic events than the late-onset group (75 patients), with 59% of the late group and only 35% of the early group free from ischemic events by 5 years after initial detection (p = 0.02), but there were no significantly correlated clinical or laboratory predictors of ischemic events. The early group had a significantly higher incidence of antecedent cytomegalovirus infection. CONCLUSIONS: We conclude that 1) accelerated graft coronary artery disease develops at variable times after heart transplantation; 2) the early appearance of graft coronary artery disease may be a marker of intrinsically more aggressive disease; 3) cytomegalovirus infection is associated with earlier onset of graft coronary artery disease. Patients with early development of graft coronary artery disease should potentially be given priority for interventional strategies as they are developed.

The Chinese version of the Brief Pain Inventory (BPI-C): its development and use in a study of cancer pain.

We describe the development of a Chinese version of the Brief Pain Inventory (BPI-C) and demonstrate its reliability and validity. We also report the use of the BPI-C in a three hospital study of cancer pain and its treatment. As with other language versions of the BPI, factor analysis of the BPI-C items results in a two factor solution that satisfies the criteria of reproducibility, interpretability and fit in a confirmatory setting. The first factor consists of the four pain severity scales, while the seven pain interference scales comprised the second factor. The BPI-C proved to be a reliable measure of both the severity and impact of pain in patients with cancer. Coefficient alpha for the pain severity and pain interference items were 0.894 and 0.915, respectively. The sample (N = 147) was gathered at three cancer treatment hospitals in Beijing. The patients from these hospitals reported higher levels of pain severity and pain interference compared with patients in similar studies done at the time (1991-1992) in the United States and France. This was in keeping with the finding that a larger proportion (67%) of the cancer patients in these Beijing hospitals were judged to have inadequate analgesia as assessed by the Pain Management Index (PMI), an estimate of adherence to the World Health Organization (WHO) guidelines for cancer pain management.

Retransplantation for severe accelerated coronary artery disease in heart transplant recipients.

Development of accelerated coronary artery disease (CAD) in the cardiac allograft is one of the major causes of late graft failure in heart transplant recipients. At the Stanford University Medical Center 356 heart transplant procedures were performed in 329 patients by the end of January 1985. Eighty-nine of these patients developed evidence of transplant CAD. Twenty retransplant procedures, including 2 third transplants, were performed in 19 of the 89 patients because of transplant CAD. The graft survival rates after the second transplant were 55%, 25% and 10% after 1, 2 and 5 years, respectively. Nine of these retransplant patients currently survive, the longest for 5.5 years. To examine potential risk factors for development of severe transplant CAD, these 20 retransplant procedures were compared with 113 transplant recipients who had no evidence of transplant CAD on annual coronary arteriograms. An excess of rejection episodes (3 +/- 2 vs 2 +/- 1 episodes/patient, p = 0.02), elevated total cholesterol (266 +/- 78 vs 225 +/- 47 mg/dl, p = 0.002) and higher low-density lipoprotein levels (176 +/- 88 vs 137 +/- 46 mg/dl, p = 0.009) were noted in the transplant CAD retransplant group. Five of 11 retransplant recipients who survived greater than 1 year again developed transplant CAD. Characteristic morphologic features and rapid progression of CAD in the second graft were similar to those in the primary graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute myocardial infarction in cardiac transplant recipients.

To characterize the clinical and pathologic features of acute myocardial infarction (AMI) in cardiac transplant recipients, 22 Stanford patients who had 25 documented infarcts at a mean of 3.86 years after transplantation were reviewed. Symptoms included chest pain (2), arm pain (3), weakness (16), dyspnea (11) and palpitations (8). Three episodes were clinically silent, detected only as new electrocardiographic changes during routine follow-up. Of 18 patients hospitalized with symptoms, only 7 had electrocardiographic changes of typical Q-wave AMI; 5 had nonspecific ST-segment changes and 2 had no documented changes. Two had old Q waves. Twelve of the 18 were misdiagnosed at admission as having infection or congestive heart failure. Serial creatine phosphokinase levels were obtained in 13 patients, and values were elevated in 8. Six of 25 AMI episodes were associated with development of congestive heart failure and 4 others led to development of cardiogenic shock. Seven patients died during the acute phase of infarction, 12 were retransplanted from 2 days to 6 months after infarct and 1 died suddenly after discharge. Two healed myocardial infarctions of unknown duration were found at autopsy or on explantation in patients not clinically suspected of having an AMI. All infarcts occurred in patients known to have angiographic evidence of transplant coronary artery disease, based on annual coronary arteriography. At autopsy or explantation all hearts were found to have characteristic diffuse concentric coronary artery narrowing, and 4 (18%) had an unusual pattern of multiple foci of nontransmural AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Accelerated graft coronary artery disease: diagnosis and prevention.

Accelerated graft coronary artery disease (CAD) has become a major factor limiting survival among long-term heart transplant survivors. Currently 14%, 37%, and 50% of patients treated with triple therapy have angiographically apparent accelerated graft CAD at 1, 3, and 5 years after transplantation. Because cardiac allografts are denervated, transplant recipients generally do not experience angina pectoris. Therefore accelerated graft CAD may present as silent myocardial infarction, congestive heart failure, or ventricular arrhythmia leading to syncope or sudden death. Noninvasive tests for CAD have been insensitive for the detection of accelerated graft CAD because of the diffuse nature of the disease. Coronary arteriographic characteristics of accelerated graft CAD are a mixture of typical focal atherosclerotic lesions and unusual diffuse, concentric, and longitudinal narrowing prominent in middle to distal coronary vessels, with distal vessel obliteration and lack of collateral vessel formation. The presence and severity of accelerated graft CAD may be underestimated by routine angiography because of its diffuse and concentric nature. Quantitative arteriography has become an important technique to assess the progression of accelerated graft CAD. Intravascular ultrasound imaging can detect even earlier development of intimal thickening. CAD risk factor modification has had little impact on the overall incidence. We initiated a randomized study of diltiazem versus no calcium blocker to determine if this may prevent accelerated graft CAD. Patients have undergone early postoperative and annual quantitative coronary angiography since inception of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of angiographic disease by intracoronary ultrasonographic findings in heart transplant recipients.

BACKGROUND: Intracoronary ultrasonography has proven to be a more sensitive test than angiography for the detection of intimal thickening in transplant recipients. However, the prognostic significance of the intimal thickening detected by intracoronary ultrasonography has not been proven. METHOD: During a 1-year period, 70 transplant recipients without angiographically apparent coronary artery disease underwent intracoronary ultrasonography examination. For each intracoronary ultrasonography study an intimal index, defined as the ratio of the plaque area to the area within the media, was measured for the most diseased segment imaged. The subsequent annual follow-up angiograms of these 70 patients were reviewed for the development of visually apparent coronary artery disease. The time since transplantation for the 70 patients without angiographically apparent coronary artery disease ranged from 1 to 15 years, with a mean of 4.2 years an median of 3.9 years. Mean duration of angiographic follow-up was 2.0 years (range 1 to 3 years). RESULTS: Angiographically apparent coronary artery disease developed on follow-up angiograms in 13 of the 70 patients, with a mean time to development of 1.5 years. Four of 46 patients (9%) with an intimal index < 0.3 subsequently had angiographically apparent coronary artery disease, whereas of 25 patients (36%) with an intimal index > or = 0.3 subsequently had angiographically apparent coronary artery disease. Odds ratio for future angiographically apparent coronary artery disease between patients with an intimal index > or = and intimal index < 0.3 was 5.9 (p < 0.01 by Fisher's Exact test). In a subgroup of 22 patients more than 5 years after transplantation at the time of intracoronary ultrasonography, 12 had an intimal index < 0.3 and 10 had an intimal index > or = 0.3. In this subgroup none of the 12 patients with an intimal index < 0.3 had angiographically apparent coronary artery disease and only 1 of the 10 with an intimal index > or = 0.3 had angiographically apparent coronary artery disease (difference not significant). CONCLUSIONS: The presence of moderate to severe intimal thickening by intracoronary ultrasonography is predictive of the future development of angiographically apparent coronary artery disease among patients more than 1 year and less than 5 years after transplantation. This same degree of intimal thickening may not carry the same prognostic significance among patients greater than 5 years after transplantation without the development of angiographically apparent coronary artery disease.