Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP.</p><p><b>METHODS</b>One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) < 35%, n = 56) or slow hemodilution (HCT > or = 35%, n = 59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined.</p><p><b>RESULTS</b>The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P < 0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4 +/- 1.9) days) compared with the slow hemodilution group ((10.2 +/- 2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P < 0.05).</p><p><b>CONCLUSIONS</b>Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.</p>

Investigation of distribution of bacteria and fungi in severe acute pancreatitis / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the spectrum of bacteria and fungi in different sites in severe acute pancreatitis (SAP).</p><p><b>METHODS</b>The prospective study was performed in 205 patients with SAP treated from January 2000 to December 2008. The Infection rate of bacteria and fungi was observed prospectively in pancreatic necrosis and(or) pus form abdomen, body fluids and deep vein catheter in SAP. Body fluids and pancreatic necrosis were cultured twice a week. Central venous catheter was cultured when it had been placed for two weeks. Blood was cultured for bacteria and fungi when body temperature was more than 39 degrees C. Constituent ratio of bacteria and fungi was observed in different sites and in all sites within 28 days after onset of SAP.</p><p><b>RESULTS</b>There were 937 pathogens, among which infection rates of gram-negative bacteria was higher than gram-positive bacteria and fungi (P < 0.05), the infection rates of gam-positive bacteria and fungi were similar. Infection rates of gram-negative bacteria in pancreatic necrosis (55.2%), bile (55.4%), blood (68.1%) and central venous catheter (44.4%) were increased significantly (P < 0.05) compared with gram-positive bacteria and (30.2%, 33.9%, 23.4%, 38.9%) and fungi (14.6%, 10.7%, 8.5%, 16.7%); however, infection rate of fungi (59.6%) was increased significantly (P < 0.05) compared with gram-negative bacteria (24.0%) and gram-positive bacteria (16.3%) in urine; infection rate of gram-negative bacteria (53.2%) was significantly higher (P < 0.05) than that of fungi (27.1%) and gram-positive bacteria (19.7%) in sputum. Infection rate of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) in gram-negative bacteria in pancreatic necrosis, bile, blood, central venous catheter and sputum was significantly higher than that of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae) (P < 0.01); infection rate of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli) was higher significantly (P < 0.01) than that of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii). Infection rate of staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus was significantly higher (P < 0.05) than that of Enterococcus faecalis and Enterococcus faecium in pancreatic necrosis and sputum;but infection rate of Enterococcus faecium in bile and urine was significantly higher than other gram-positive bacteria (P < 0.05). There was not difference among gram-positive bacteria;however, infection rate of Staphylococcus epidermidis in central venous catheter was increased significantly (P < 0.05). Infection rate of candida mycoderma in pancreatic necrosis, bile, urine and sputum was significantly higher than that of tricho bacteria (P < 0.05). The peak of infection rate of microbes in body fluid was within 2 to 3 weeks.</p><p><b>CONCLUSIONS</b>Constituent ratio in gram-negative, gram-positive bacteria and fungi as well as their species in different sites is diverse. The peak of infection rate of microbes is 2 to 3 weeks after onset of the disease.</p>

Detection of early organ dysfunction for the selection of treatment strategy on severe acute pancreatitis / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the severity related influencing factor and treatment strategy of severe acute pancreatitis with early organ dysfunction.</p><p><b>METHODS</b>From July 2007 to December 2008, 167 patients with severe acute pancreatitis were treated in the Surgical Department of Ruijin Hospital. The relationships between the happening of early organ dysfunction and outcome of the patients were observed, with operative or nonoperative treatment strategy.</p><p><b>RESULTS</b>Among 167 patients, 68 patients have early organ dysfunction, in which 39 with single organ dysfunction and 29 with multiple organ dysfunction. The early organ dysfunction were involved in 47.1% in cardiovascular system, 35.3% in lung and 29.4% in kidney. Aging (P < 0.05) and higher APACHE II score (P < 0.05) predicted a poor prognosis, which were benefit from early operation.</p><p><b>CONCLUSIONS</b>The mortality of the patients with SAP is related to age, and the degree of organ dysfunction as well. In the first phase of the disease, the selection of operation depends on the trends and the degree of early organ dysfunction before infected necrosis happens, with the aid of SOFA score as a scale.</p>

Strategy of treatment with high-volume hemofiltration on severe acute pancreatitis and fulminant acute pancreatitis / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate strategy of treatment of hemofiltration on severe acute pancreatitis (SAP) and fulminant acute pancreatitis (FAP).</p><p><b>METHODS</b>One hundred and thirty patients with SAP and eighty-one patients with FAP treated with hemofiltration (HF) were prospectively observed from March 1997 to December 2008. Indications for HF, variables (time interval for hemofiltration), mode, therapeutic dosage, blood rate, heparin dosage and components of hemofiltration, therapeutic efficacy (time of disapearance of abdominal pain, intra-abdominal pressure and survival rate) and complications (incidence of bleeding and blood infection).</p><p><b>RESULTS</b>All patients underwent high volume hemofiltration (HVHF) or hemodialysis-filtration (HDF) within 72 hours after onset of the disease. Dose of SAP and FAP was (53 +/- 6) mlxkg(-1)xh(-1) and (59 +/- 10) mlxkg(-1)xh(-1) (P < 0.05), respectively. Rate of short veno-venous hemofiltration in SAP (76.9%) was higher than that of FAP (38.3%) (P < 0.05); however, rate of continuous veno-venous hemofiltration (23.1%) was lower than that of FAP (37.0%) (P < 0.05). Rate of HDF was much higher in FAP than that of SAP. Low molecular weight heparin and heparin were both available to anticoagualte;but dosage required in patients with FAP was much higher than that of SAP (P < 0.05). Time intervals for amelioration of abdominal pain in SAP and FAP were (9 +/- 6) h and (15 +/- 10) h, respectively. Itra-abdominal pressure was decreased significantly at the end of hemofiltration compared to prior to hemofiltration in SAP and FAP (P < 0.05). Level of serum triglyceride decreased abruptly after adsorption (P < 0.05). Rate of operation within 28 days in SAP (73.8%) was lower than FAP (87.7%). The in-hospital survival rates in SAP and FAP were 88.5% and 67.9%, respectively. Amount of platelet decreased in patients with blood flow rate less than 240 ml/min was higher than that of more than 240 ml/min (P < 0.05). And incidence of blood stream infection and bleeding increased significantly (P < 0.05).</p><p><b>CONCLUSIONS</b>HVHF and HDF used in SAP and FAP patients underwent conservative treatment within 72 hours, respectively, can increase survival rate significantly.</p>

Fluid therapy for severe acute pancreatitis in acute response stage / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP.</p><p><b>METHODS</b>Seventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group (Group I, n = 36) and a controlled fluid expansion group (Group II, n = 40). Hemodynamic disorders were either quickly (fluid infusion rate was 10 - 15 ml x kg(-1) x h(-1), Group I) or gradually improved (fluid infusion rate was 5 - 10 ml x kg(-1) x h(-1), Group II) through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome (ACS), sepsis, and survival rate were obtained.</p><p><b>RESULTS</b>The two groups had statistically different (P < 0.05) time intervals to meet fluid expansion criteria (Group I, 13.5 +/- 6.6 hours; Group II, (24.0 +/- 5.4) hours). Blood lactate concentrations were both remarkably lower as compared to the level upon admission (P < 0.05) and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I (35.6% +/- 6.8%) than in Group II (38.5% +/- 5.4%) (P < 0.01). Amount of crystalloid and colloid in group I ((4028 +/- 1980) ml and (1336 +/- 816) ml) on admission day was more than those of group II ((2472 +/- 1871) ml and (970 +/- 633) ml). No significant difference was found in the total amount of fluids within four days of admission between the two groups (P > 0.05). Total amount of fluid sequestration within 4 days was higher in Group I ((5378 +/- 2751) ml) than in Group II ((4215 +/- 1998) ml, P < 0.05). APACHE II scores were higher in Group I on days 1, 2, and 3 (P < 0.05). Rate of mechanical ventilation was higher in group I (94.4%) than in group II (65%, P < 0.05). The incidences of abdominal compartment syndrome (ACS) and sepsis were significantly lower in Group II (P < 0.05). Survival rate was remarkably lower in Group I (69.4%) than in Group II (90%, P < 0.05).</p><p><b>CONCLUSIONS</b>Controlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset.</p>

Strategy of controlling fluid resuscitation for severe acute pancreatitis in acute phase / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the strategy of controlling fluid resuscitation for severe acute pancreatitis (SAP) in acute phase.</p><p><b>METHODS</b>From March 2001 to January 2006, 83 patients meeting for experimental criteria were included in this clinical trial. They were divided into early fluid expansion group (Group I, within 24 h after admission, 21 patients), middle fluid expansion group (Group II, within 25 - 48 h, 35 patients) and late fluid expansion group (Group III, within 49 - 72 h, 27 patients). Parameters of treatment of fluid therapy within 4 d after admission were observed. Serum lactic level was measured on admission and on meeting for criteria of fluid expansion. APACHEII scores, operation rate within 2 weeks, rate of mechanical ventilation, rate of ACS and survival rate were observed.</p><p><b>RESULTS</b>Time interval for meeting fluid expansion criteria in Group I, Group II, Group III was (13 +/- 6) h, (38 +/- 5) h and (61 +/- 8) h, respectively. And there was statistical significance among them (P < 0.05). HCT (%) in Group I (33 +/- 6)% was lower than that of Group II (40 +/- 6)% and Group III (42 +/- 11)% significantly (P < 0.01) at the first day after admission; and there was no statistical significance between Group II and Group III. The amount of crystal and colloid infused in Group I (4014 +/- 2887) ml and (1220 +/- 705) ml at the day of admission was more than those of Group II (2366 +/- 1959) ml and (821 +/- 600) ml and Group III (2615 +/- 1574) ml and (701 +/- 585) ml (P < 0.01); but there was not different between Group II and Group III (P > 0.05). The ratio of colloid and crystal in Group III at the day of admission was lower than those of Group I and Group II (P < 0.05). The total amount of fluid infused was not different among 3 groups for the 4 d (P > 0.05). And infusion rate at the day of admission in Group I was more rapid than those of Group II and Group III (P < 0.05); and there was no difference between Group II and Group III (P > 0.05). The total amount of fluid sequestration in Group II for the 4 d was lower than those of Group I and Group III (P < 0.05); and there was no statistical significance between Group I and Group III (P > 0.05). At the first to the third day after admission APACHEII scores in Group I were higher than those of Group II and Group III (P < 0.05); and at the second and third day, APACHEII scores in Group III were higher than those of Group II (P < 0.05). Rate of mechanical ventilation in Group I (85.7%) was higher than those of Group II (37.1%) and group III (63.0%) (P < 0.05); and rate of ACS was most lowest in Group II (37.1%) (P < 0.05). Survival rate in Group I (38.1%) was lower than those of Group II (85.7%) and Group III (66.7%) (P < 0.05); and Group III was lower than that of Group II (P = 0.075).</p><p><b>CONCLUSIONS</b>Within 72 h after onset of the disease, survival rate is improved significantly through controlling fluid resuscitation and prevention of body fluid sequestration.</p>

Long-term outcome and health-related quality of life in survivors of severe acute pancreatitis / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the health-related quality of life and postdischarge long-term outcome after severe acute pancreatitis.</p><p><b>METHODS</b>The hospital records of patients with SAP discharged healthy from January 2003 to December 2003 were reviewed. The Rand 36-item Health Survey with accessory question was mailed to each patient. The means and deviations for each of eight scales scores of SF-36 were calculated, the study population scores were compared with general Chinese population; Univariate analysis was applied to determining the effects of variables such as age, sex, causes of disease, mode of treatment, frequency of surgery, financial burden, length of stay, chronic complications. Accessory questions were analyzed separately.</p><p><b>RESULTS</b>The means and deviations for each of eight scales (PF, RP, RE, BP, VT, MH, SF, GH) scores of SF-36 in SAP patients were 83 +/- 15, 62 +/- 42, 69 +/- 36, 80 +/- 15, 69 +/- 19, 72 +/- 15, 75 +/- 18, 65 +/- 18, compared with general people. Except RP and SF, the others were similar. In the ANOVA of Physical Component Summary, the three variables mode of treatment, financial burden and length of stay were included (P < 0.05), while in that of Mental Component Summary, the two variables of gender and financial burden were included (P < 0.05).</p><p><b>CONCLUSIONS</b>The health-related quality of life in SAP patients is similar to that of general people. Greater attention should be given to mode of treatment, length of stay and financial burden to improve quality of life.</p>

The characteristic of severe acute pancreatitis and the selection of the therapeutic strategy / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the clinical character and therapeutic strategy and prognosis in severe acute pancreatitis.</p><p><b>METHODS</b>From January 2001 to December 2005, 783 patients with SAP were treated. Therapeutic strategy was selected based on the preliminary scheme for diagnosis and treatment of severe acute pancreatitis by pancreatic surgery society of CMA. All the patients were divided into biliary group and non-biliary group, while 375 patients in biliary group, with 182 patients treated operatively and 193 patients treated nonoperatively; and 408 patients in non-biliary group, with 147 patients treated operatively and 261 patients treated nonoperatively.</p><p><b>RESULTS</b>There were 698 survivals, the overall survival rate was 89.1%. 357 survivals in the biliary SAP group, the survival rate was 95.0%, in which 171 survivals from operation treated cases, with the survival rate of 94.0%, and 186 survivals from non-operation treated cases, with the survival rate of 96.4%; 341 survivals in the non-biliary SAP group, the survival rate was 84.0%, in which 110 survivals from operation treated cases, with the survival rate of 74.8%, and 231 survivals from non-operation treated cases, with the survival rate of 88.5%. 48.3% patients of the survival group had organ dysfunction, and 18.3% patients had multiple organ dysfunctions, while 100% patients of the death group had organ dysfunction, and 97.6% patients had multiple organ dysfunction. Respiratory dysfunction was found to be the most common cause totally followed by nerve system dysfunction and shock, with the rates of 26.3%, 11.7% and 10.3%, respectively. Respiratory dysfunction, renal dysfunction and cardiac dysfunction are most commonly in death group, with the rate of 94.1%, 60.0% and 60.0%, respectively. The rate of fungi infection in the survival group and death group were 8.9% and 37.6%. The rates of alimentary tract fistula in the survival and death group were 0.9% and 14.1%, respectively.</p><p><b>CONCLUSIONS</b>The therapy aiming at the cause for biliary SAP and the operation aiming at infected pancreatic necrosis is helpful to improve curative rate; MODS is the main cause of death in severe acute pancreatitis. Respiratory dysfunction, renal dysfunction and cardiac dysfunction are high risk factors.</p>

Study on the position of genes responsible for gallstone disease in Chinese population / 中华外科杂志

<p><b>OBJECTIVE</b>To search the susceptibility genes of gallstone disease in Chinese population.</p><p><b>METHODS</b>A genome wide scan was performed in twelve families with gallstone disease using fluorescence-labeled microsatellite markers. Genehunter and Batchlink of Linkage package were used for non- parameter and parameter linkage analysis to search the linkage loci on chromosomes.</p><p><b>RESULTS</b>Four loci of D3S1266, D4S406, D9S1682 and D11S902 showed suggestive evidence for linkage. nonparametric linkage analysis (NPL)-score of D4S406 and D9S1682 was 1.77 (P = 0.05) and 1.92 (P = 0.04) respectively. The corresponding logarithm of the odds ratio (LOD)-score of D3S1266, D9S1682 were 1.35 and 2.07, and showed a rise of LOD-score from 1.35 to 2.71, 2.07 to 2.40 respectively when families with later-found patients or with higher triglyceride level were analyzed alone. Transmitted disequilibrium test of D11S902 showed a P-value of 0.0027.</p><p><b>CONCLUSIONS</b>Chromosome 3, 4, 9 and 11 may contain genes involved in gallstone disease in Chinese population, and chromosome 3, 9 may hide genes that are liked to gallstone disease in families with later-found patients or with higher triglyceride concentration.</p>

Therapeutic experience of fulminant acute pancreatitis in acute response stage / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate therapeutic strategy of fulminant acute pancreatitis (FAP) in acute response stage.</p><p><b>METHODS</b>Sixty-four patients were divided into Death group (27 patients) and Survival group (37 patients). The time course of shock and recovery of enteral function, parameters of fluid resuscitation, PaO(2)/FiO(2) and AaDO(2) at 24 hours prior to mechanical ventilation, rate of continuous venovenous hemofiltration (CVVH) and abdominal compartment syndrome (ACS), severity of the disease in the acute response stage were investigated. And the effect of surgical manner and time on the prognosis was also analyzed.</p><p><b>RESULTS</b>Compared with Survival group, the time course of shock and recovery of enteral function in Death group were prolonged significantly (P < 0.05). Between the groups, there was no difference in the amount of crystal fluid infused from admission to 72 hours after, but the amount of colloid fluid infused and ratio of amount of colloid and crystal fluid in Survival group were higher (P < 0.05). The amount of fluid retention in third space from admission to 72 hours after in Death group was higher than that of Survival group significantly (P < 0.05). The fluid infusing rate in Survival group in the first day of admission was faster than Death group (P < 0.05). PaO(2)/FiO(2) and AaDO(2) in 24 hours prior to mechanical ventilation in Death group were negatively changed significantly. Within 72 hours after the onset of the disease, the rate of CVVH in Survival group was higher than Death group. Incidence rate of ACS and the APACHEII scores within 72 hours after admission in Death group were higher than in Survival group. The cure rate of the patients operated in the day 7 to day 14 after admission was higher than that of patients operated prior and post this period. Time for the first operation in operated patients was earlier than patients received minimally invasive drainage (MID) and its cure rate was lower than that of MID Group.</p><p><b>CONCLUSIONS</b>It is the key point to shorten the time course of ischemia, to control persistent systemic inflammatory response syndrome (SIRS) and to adopt reasonable surgical intervention in acute response stage for FAP.</p>

The surgical treatment of the solid-pseudopapillary tumor of pancreas: report of 21 cases / 中华外科杂志

<p><b>OBJECTIVE</b>The surgical therapies and prognoses on 21 solid-pseudopapillary tumors (SPT) of pancreas were summarized in our center.</p><p><b>METHODS</b>Twenty-one SPTs were retrospectively studied and divided into two groups, the complete capsular group and the incomplete one. The analyses were performed by SAS6.12 Stat. software.</p><p><b>RESULTS</b>There are no tumor recurrences in all patients. There are significant difference between operative types in radical resection and the tumor position of the pancreas (P = 0.038). There are also significant differences between the capsular integrity and the course of the diseases (P = 0.029), and the possible malignant cells by the frozen section examination (P = 0.001), and the size of the tumor (P = 0.0004). The judgement on the capsular integrity of the tumor could directly effect the adoptable operative types (P = 0.001).</p><p><b>CONCLUSIONS</b>The surgical resection is good treatment for the SPT, which has satisfying prognosis.</p>

Study on the characteristics of inheritance and epidemiology in one pedigree with gallstone disease / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the characteristics of inheritance and epidemiology of gallstone disease in one pedigree.</p><p><b>METHODS</b>A gallbladder disease-specific questionnaire was administered to all family members to ascertain histories of cholecystectomy and other medical conditions as well as anthropometrical data. Laboratory examination and ultrasonography were performed to determine the existence of gallstone.</p><p><b>RESULTS</b>One hundred and thirteen members of four generations in the index family were enrolled in the study. The prevalence of gallstone in females (34.48%) was higher than in males (23.64%) but with no significant difference. The prevalence in the second and third generations (52%) was higher than in others (20%) (P < 0.05). The heritability and standard error showed as 86.38% +/- 46.46% in I generations. Body mass index, histories of hypertension, hyperlipidemia and blood glucose were positively related to gallstone disease (P = 0.012, < 0.01, 0.017, 0.043, respectively) in this family. Gallstone disease was not significantly related to history of diabetes, daily alcohol or diet habit. Plasma cholesterol and triglyceride levels were not correlated with gallstone disease.</p><p><b>CONCLUSION</b>Gallstone disease presented aggregation in the family and was in accordance with the characteristics of autosomal dominant inheritance. Being female, obesity, hypertension and history of hyperlipidemia might serve as risk factors to this family.</p>

Clinical misdiagnosis of solid pseudopapillary tumour of pancreas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Since being reclassified by WHO in 1996, solid pseudopapillary tumour (SPT) of pancreas has been recognized as the internationally accepted name. Clinicians are lacking in knowledge of this rare disease so the misdiagnosis and inappropriate therapy are hard to avoid. The clinic data on 22 patients were summarized to study the misdiagnosis and treatment of a sample of SPTs.</p><p><b>METHODS</b>Twenty-two female patients with SPT were studied retrospectively and divided into two groups, the misdiagnosed group and the correctly diagnosed one. The analyses were performed with Fisher test with accurate probability for categorical data, and Kruskal-Wallis test for ranked data.</p><p><b>RESULTS</b>The rate of misdiagnosis in this sample was 45.5%. The misdiagnosed SPTs were apt to be the incomplete capsule ones (P = 0.020), which resulted in obvious difficulties during operation (P = 0.024). In the misdiagnosed SPT group, the medical expenses increased significantly (P = 0.042), and the number of days in hospital greater than in correctly diagnosed group (P = 0.041).</p><p><b>CONCLUSIONS</b>Although SPT has low malignancy with excellent prognosis after surgical treatment in most patients, the misdiagnosis of SPT increases the social and economic burdens on patients. It is important to analyse the causes of misdiagnosis.</p>