SARS-CoV-2 Vaccination Response in Japanese Patients with Autoimmune Hepatitis: Results of Propensity Score-Matched Case-Control Study.

BACKGROUND/AIMS: Although the World Health Organization declared the end of the public health emergency of international concern focusing on COVID-19 in May 2023, this bothersome virus continues to mutate, and the possibility of the emergence of mutant strains with high infectivity and severe disease rates has not disappeared. Thus, medical evidence must be accumulated, which is indispensable for protecting both patients under immunosuppressive treatments and the healthy population. This study examined SARS-CoV-2 vaccination responses in Japanese patients with autoimmune hepatitis (AIH) compared with healthy controls. METHODS: This observational study registered 22 patients with histologically diagnosed AIH and 809 healthy controls in our hospital. Their Elecsys anti-SARS-CoV-2 spike antibody concentrations before and after vaccination were evaluated. RESULTS: In this study, 72.7% and 18.2% of patients with AIH received steroids and azathioprine, respectively. Significant negative correlations were found between age and anti-SARS-CoV-2 spike antibody concentration in both groups; however, no sex differences were found. Although anti-SARS-CoV-2 spike antibody concentration was drastically augmented after the second vaccination (p < 0.05) in the AIH group, these levels were significantly lower than those in the controls (p < 0.05). In the age- and sex-matched analysis, the population ratio with a minimum response (≤100 binding antibody units (BAU/mL) was higher among patients with AIH than among controls 26 weeks after the second vaccination (44% vs. 7%, p < 0.05). CONCLUSIONS: The anti-SARS-CoV-2 spike antibody concentration in AIH patients was significantly lower than that in controls after the second vaccination. Continued and widespread vaccination, particularly for patients requiring medical immunomodulation, is recommended.

Efficacy of Serum Ferritin-Zinc Ratio for Predicting Advanced Liver Fibrosis in Patients with Autoimmune Hepatitis.

Background/Aims: The search for noninvasive biomarkers that can efficiently estimate the extent of liver fibrosis progression is ongoing. Although Fibrosis-4 (FIB-4), the aspartate transaminase-to-platelet ratio index (APRI), and the Forns index have been reported as useful biomarkers, their investigation in autoimmune hepatitis (AIH) is limited. This study aimed to examine the usefulness of these serological indices and a newly developed index in predicting liver fibrosis progression in AIH. Methods: The study analyzed data from 190 patients diagnosed with AIH at our institution between 1990 and 2015. Their histological liver fibrosis progression and clinical long-term prognosis were evaluated retrospectively (cohort 1). In 90 patients, receiver operating characteristic (ROC) curves were compared to choose severe fibrosis cases with respect to existing indices (FIB-4, APRI, and Forns index) and the ferritin-zinc ratio (cohort 2). Results: In cohort 1, liver-related death and hepatocellular carcinoma rates were significantly higher in the severe (n = 27) than in the mild (n = 63) fibrosis group (p = 0.0001 and 0.0191, respectively). In cohort 2, liver-related death in the severe fibrosis group was significantly frequent (p = 0.0071), and their ferritin-zinc ratio was higher (median 2.41 vs. 0.62, p = 0.0011). ROC analyses were performed to compare the ability of the ferritin-zinc ratio, FIB-4, APRI, and the Forns index to predict severe and mild fibrosis. Accordingly, areas under the ROC were 0.732, 0.740, 0.721, and 0.729, respectively. Conclusions: The serum ferritin-zinc ratio can noninvasively predict liver fibrosis progression in AIH and be applied to predict long-term prognosis.

Chronic active EBV infection in refractory enteritis with longitudinal ulcers with a cobblestone appearance: an autopsied case report.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is defined as Epstein-Barr virus (EBV)-positive T/NK cell-related neoplasia, and its major clinical symptom is systemic inflammation presenting as infectious mononucleocytosis, whereas enteritis and diarrhea are minor clinical symptoms. The complex mixture of tumorigenic processes of EBV-positive cells and physical symptoms of systemic inflammatory disease constitutes the varied phenotypes of CAEBV. Herein, we describe a case of CAEBV that was initially diagnosed as Crohn's disease (CD) based on ileal ulcers and clinical symptoms of enteritis. CASE PRESENTATION: A 19-year-old woman complained of abdominal pain and fever. Blood examination showed normal blood cell counts without atypical lymphocyte but detected modest inflammation, hypoalbuminemia, slight liver dysfunction, and evidence of past EBV infection. The esophagogastroduodenoscopic findings were normal. However, colonoscopy revealed a few small ulcers in the terminal ileum. The jejunum and ileum also exhibited various forms of ulcers, exhibiting a cobblestone appearance, on capsule endoscopy. Based on these clinical findings, she was strongly suspected with CD. In the course of treatment by steroid and biologics for refractory enteritis, skin ulcers appeared about 50 months after her initial hospital visit. Immunohistology of her skin biopsy revealed proliferation of EBV-encoded small RNA (EBER)-positive atypical lymphocytes. We retrospectively assessed her previous ileal ulcer biopsy before treatment and found many EBER-positive lymphocytes. Blood EBV DNA was also positive. Therefore, she was diagnosed with extranodal NK/T-cell lymphoma with CAEBV-related enteritis rather than CD. She was treated with cyclosporine and prednisolone combination therapy for CAEBV-related systemic inflammation and chemotherapy for malignant lymphoma. Unfortunately, her disease continued to progress, leading to multiple organ failure and death at the age of 23 years. CONCLUSION: Clinicians need to remember the possibility of CAEBV as a differential diagnosis of refractory enteritis. Enteritis with intestinal ulcer is a rare symptom of CAEBV, and it is impossible to acquire a definitive diagnosis by ulcer morphology only. In cases where the possibility of CAEBV remains, tissue EBVR expression should be checked by in situ hybridization and blood EBV DNA.

Surgical treatment of abdominal aortic aneurysm associated with horseshoe kidney: symphysiotomy using harmonic focus.

Coexistence of horseshoe kidney and abdominal aortic aneurysm (AAA) is a rare entity that presents a technical challenge to vascular surgeons. How to approach such an AAA with horseshoe kidney and whether to divide the renal isthmus remains a controversial issue. We report here the successful surgical repair of an AAA with horseshoe kidney via the transperitoneal approach with division of the renal isthmus by Harmonic Focus, which allowed easy division of the isthmus without bleeding. Harmonic Focus, a hand-held type of harmonic scalpel, was thus useful in symphysiotomy of the horseshoe kidney.

[A case of infectious mononucleosis with splenic infarction].

A 22-year-old man complaining of persisting high fever and right hypochondralgia was admitted to our hospital for infectious mononucleosis with splenic infarction detected by computed tomography. The splenic infarction deteriorated with a marked elevation of inflammatory parameters. This necessitated the commencement of methylprednisolone pulse therapy, resulting in prompt amelioration of inflammation and a reduction in cytokine levels. Including our case, only 9 cases of mononucleosis with splenic infarction have been reported to date; however, splenic infarction should be considered because it is a significant complication of infectious mononucleosis.

A foot ulcer caused by the use of an angio-seal arterial closure device after percutaneous transluminal angioplasty: a case report.

Although the Angio-Seal arterial closure device is widely used for preventing bleeding and facilitating early ambulation after arterial puncture, it is also associated with unique complications, such as stenosis, occlusion, or peripheral embolism. We report the first case of a foot ulcer that developed 70 days after an Angio-Seal application. The collagen sponge component accidently positioned itself in the arterial lumen and was not absorbed. A foreign body reaction was observed microscopically. In patients with arteriosclerosis, the Angio-Seal device should be used carefully; post procedural monitoring is necessary after implantation.

Efficient formation of giant liposomes through the gentle hydration of phosphatidylcholine films doped with sugar.

Giant liposomes, or giant vesicles, are cell-size (approximately 5-100 microm) compartments enclosed with phospholipid bilayers, and have often been used in biological research. They are usually generated using hydration methods, "electroformation" and "gentle hydration (or natural swelling)", in which dry lamellar films of phospholipids are hydrated with aqueous solutions. In gentle hydration, however, giant liposomes are difficult to prepare from an electrostatically neutral phospholipid because lipid lamellae cannot repel each other. In this study, we demonstrate the efficient formation of giant liposomes using the gentle hydration of neutral phospholipid (dioleoyl phosphatidylcholine, DOPC) dry films doped with nonelectrolytic monosaccharides (glucose, mannose, and fructose). A mixture of DOPC and such a sugar in an organic solvent (chloroform/methanol) was evaporated to form the films, which were then hydrated with distilled water or Tris buffers containing sodium chloride. Under these conditions, giant liposomes spontaneously formed rapidly and assumed a swollen cell-sized spherical shape with low lamellarity, whereas giant liposomes from pure DOPC films had multilamellar lipid layers, miscellaneous shapes and smaller sizes. This observation indicates that giant unilamellar vesicles (GUVs) of DOPC can be obtained efficiently through the gentle hydration of sugar-containing lipid dry films because repulsion between lipid lamellae is enhanced by the osmosis induced by dissolved sugar.

A case of pulmonary embolism after abdominal angiography.

The patient was a 72-year-old woman who had been diagnosed with cholecystolithiasis and had undergone laparoscopic cholecystectomy. Since the postoperative pathologic diagnosis was a gallbladder cancer with a depth of wall penetration of subserosa, she was admitted to Kurume University Hospital for a second-look operation. After admission, abdominal angiography was performed with a right femoral arterial puncture. After the release of inguinal compression with a belt, chest pain and difficulty in breathing appeared. Despite her normal blood pressure, arterial blood gas analysis showed a PO2 of 74.7 mmHg and a PCO2 of 41.5 mmHg, representing a slight decrease in PO2. Chest X-rays showed an increased cardiothoracic ratio and decreased lucency in the left upper lung field. The electrocardiogram revealed atrial premature contraction. Cardiac ultrasound did not show expansion of the right heart and blood vessels or abnormal structures in the main pulmonary artery. Since lung perfusion scintigraphy revealed perfusion defects in the left upper to middle and right upper lung fields, acute pulmonary embolism was diagnosed, and oxygen inhalation, thrombolytic, and anticoagulant therapy were instituted immediately. The symptoms improved the following day, but 240,000 u/day of urokinase was administered for 5 days, and 1,500 u/day of heparin for 10 days. On lung perfusion scintigrams 6 days later, the defects had disappeared. Moreover, no definite abnormal shadows were noted on chest X-rays. Radical surgery for gallbladder cancer was performed 3 weeks later. Considering the possible development of pulmonary embolism, we felt the need for careful management if the patient is released from bed rest after abdominal angiography.

A case of benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma.

We report a patient with benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma. A 66-year-old woman consulted a local physician because of general fatigue. Blood biochemical tests showed increased levels of biliary tract enzymes. Abdominal ultrasonography (US) revealed tapering and blockage of the midportion of the bile duct and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography (MRCP) demonstrated obstruction of the midportion of the bile duct. Later, because a marked increase in biliary tract enzymes and jaundice appeared, percutaneous transhepatic biliary drainage (PTBD) was performed. Post-PTBD cytological examination of bile was negative for cancer. A third biopsy showed slight hyperplasia with no malignant findings. Recholangiography, performed through PTBD, suggested gradual improvement of bile duct stricture, but could not completely exclude the possibility of malignancy; thus, resection of the bile duct including the stricture site was performed, and the resected specimen was submitted for intraoperative frozen section examination. Histopathological diagnosis did not reveal malignant findings. After cholecystectomy and bile duct resection, hepaticojejunostomy (Roux-en-Y) was performed. Because only erosion and desquamation of the mucosal epithelium and mild submucosal inflammatory cell infiltration and fibrosis were observed, chronic cholangitis was diagnosed histopathologically. Surgical resection of the bile duct should be considered for potentially malignant stricture of the bile duct.

Evaluation of resection of the papilla of Vater for the treatment of cancer in the papilla of Vater.

We evaluated the resection of the papilla of Vater performed in patients with cancer in the papilla of Vater. The subjects were 6 patients who underwent resection of the papilla of Vater between January 1969 and December 2001. The patients aged 57-87 years consisted of 3 males and 3 females. The maximal diameter of the tumors was 0.5 cm in 1 patient, 1.5 cm in 3 patients, and 2.0 cm in 2 patients. Macroscopically, the tumors were of the protruded type (exposed) in 3 patients, of the mixed type (predominant protruded type) in 2 patients, and of the ulcerative type in 1 patient. The histological depth of the tumors was up to the mucosa in 1 patient, up to the oddi in 1 patient, up to the panc0, du1 in 1 patient, up to the panc1, du2 in 1 patient, and unknown in 2 patients. Histologically, the tumors were papillotubular adenocarcinoma (pap-tub) in 4 patients and tubular adenocarcinoma of the well-differentiated type (tub1) in 2 patients. Resection of the papilla of Vater was chosen because of high risk factors such as advanced age in 2 patients, complicated severe cirrhosis and confinement to bed due to poor systemic conditions after intracerebral hemorrhage in 3 patients, and hepatic metastasis observed during surgery in 1 patient. Residual cancer cells around the excised region were positive in 4 patients and unknown in the remaining 2 patients. Of the 6 patients, 5 died within 2 years after surgery, but 1 is alive without symptoms of recurrence 7 years after surgery. The death causes were the primary disease in 3 of the 5 patients. From the viewpoint of radical treatment, resection of the papilla of Vater cannot be chosen as a reduced surgery for cancer in the papilla of Vater. However, resection of the papilla of Vater can be applied to very elderly patients and patients under poor systemic conditions, for whom pancreatoduodenectomy (PD) is considered excessively invasive due to a small diameter of tumor.

[Changes in whole blood ionized magnesium concentration during cardiac surgery employing St. Thomas' cardioplegic solution].

BACKGROUND: Although there is growing evidence to suggest that magnesium supplementation to patients undergoing cardiac surgery is beneficial, the way to administer magnesium is not established. Moreover in Japan St Thomas' cardioplegic solution, containing a high level of magnesium is widely used and the effect of such magnesium-rich cardioplegic solutions on blood magnesium concentration has not been well defined. METHODS: We measured ionized magnesium concentrations (iMg) during cardiac surgery employing St Thomas' solution. Patients were divided into four groups. Group 1 patients were adults and group 2 were children, both of whom received St. Thomas' solution. Group 3 patients underwent cardiopulmonary bypass but did not receive any cardioplegic solution. Group 4 patients underwent off-pump coronary artery bypass grafting. RESULTS: In cardioplegia group (group 1 and 2) iMg was higher than the normal reference range at periods of rewarming, immediately postbypass, and at the end of the operation. iMg at immediately postbypass was related to the total amount of cardioplegic solution. In non-cardioplegia group (group 3 and 4) progressive decrease of iMg was observed throughout the operation. CONCLUSION: Because magnesium in cardioplegic solutions has substantial effect on perioperative iMg, it is crucial to measure iMg to avoid overdose of magnesium when magnesium-rich cardioplegic solutions are employed.

Two cases of acute cholecystitis in which percutaneous transhepatic gallbladder aspiration (PTGBA) was useful.

We report 2 patients with acute cholecystitis for which percutaneous transhepatic gallbladder aspiration (PTGBA) was useful. In Case 1, the patient was a 75-year-old woman who experienced a sudden onset of back pain and upper abdominal pain at night. Abdominal ultrasound (US) showed enlargement of the gallbladder with thickening of the wall, a sonolucent layer, and a stone in the neck of the gallbladder, which led to a diagnosis of acute cholecystitis. Magnetic resonance imaging (MRI) demonstrated thickening of the gallbladder wall and 2 areas of low-intensity signal. The pain and fever persisted, for which we performed PTGBA, aspirating about 113 ml of infected bile. Subsequently, the pain and fever subsided, and abdominal US revealed a reduction in the enlargement of the gallbladder with the persistence of thickening of the wall. On the eighth day after PTGBA, open abdominal cholecystectomy was performed. In Case 2, the patient was a 56-year-old woman who had right hypochondriac pain after supper. The pain gradually increased in severity. Abdominal US showed enlargement of the gallbladder with a thickened wall, a sonolucent layer, and a gallstone in the neck of the gallbladder, which led to a diagnosis of acute cholecystitis. Magnetic resonance cholangiopancreatography (MRCP) showed enlargement of the gallbladder with no abnormalities in the common bile duct. After admission to hospital, the pain and fever persisted, for which we performed PTGBA, aspirating about 50 ml of infected bile. Subsequently, the pain and fever vanished. Abdominal US revealed a reduction in the enlargement of the gallbladder with the persistence of thickening of the wall. On the seventh day after PTGBA, laparoscopic cholecystectomy was performed. PTGBA seems useful for early alleviation of the symptoms of acute cholecystitis because of low invasiveness and ease of performance.

Surgical treatment for chronic pancreatitis: results of pancreatic duct drainage operation and pancreatic resection.

Between 1978 and 1999, 86 patients with chronic pancreatitis were surgically treated at the Surgical Department of Kurume University Hospital. Of these patients, 30 were treated by pancreatic duct drainage operation (drainage operation), while 40 were treated by pancreatic resection, and the results were compared between the two groups. In patients who underwent drainage operation, pain disappeared in 85.7%, slightly relieved in 10.7%, and not relieved in 3.6%. In patients who underwent pancreatic resection, pain disappeared in 73.4%, slightly relieved in 13.3%, and not relieved in 13.3%. Therefore, there was no significant difference in the pain-relieving effect between the two groups. However, the pain-relieving effect was poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. In addition, all patients who showed poor results for pain relief had alcoholic pancreatitis. Endocrine and exocrine functions of the pancreas were improved in 6, maintained in 2, and exacerbated in 4 patients who underwent drainage operation. In patients who underwent pancreatic resection, endocrine and exocrine function of the pancreas were improved in 3, maintained in 3, and exacerbated in 13. Therefore, endocrine and exocrine function of the pancreas were poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. Distant results in patients who underwent drainage operation were good in 75.0%, fair in 15.0%, and poor in 10.0%. In patients who underwent pancreatic resection, distant results were good in 80.0%, fair in 13.3%, and poor in 6.7%. Therefore, favorable distant results were obtained in both groups. These findings suggest that surgical techniques that preserve functions of the pancreas should be selected during surgical treatment for chronic pancreatitis. We consider that the presence or absence of main pancreatic duct dilation and the site of pancreatic lesions are important indices for selecting surgical techniques. Therefore, drainage operation consisting of pancreaticojejunostomy should be indicated for patients with main pancreatic duct dilation, while pancreatic resection should be indicated for those without main pancreatic duct dilation, those with localized pancreatic lesions, and those with suspected pancreatic cancer.

A case of gallbladder cancer associated with pancreaticobiliary maljunction.

We report a case of gallbladder cancer associated with pancreaticobiliary maljunction. The patient was a 60-year-old woman who consulted a local doctor because of discomfort in the right hypochondriac region. Abdominal ultrasonography (US) showed a gallbladder abnormality, and she was referred to Kurume University Hospital, where she was hospitalized for further study and surgery. Abdominal US revealed a sessile tumor with an irregular surface in the fundus of the gallbladder. The internal echo of the tumor was nonhomogeneous, and the structure of the gallbladder wall was partly torn. The common bile duct and the left intrahepatic bile duct were dilated. Abdominal computed tomography (CT) showed an elevated lesion with the same degree of imaging effect as that of the liver on the peritoneal side of the fundus of the gallbladder. The structure of the gallbladder was preserved, and the gallbladder was well demarcated from the surrounding tissue. No hepatic or lymph node metastases were noted. Endoscopic retrograde cholangiopancreatography (ERCP) visualized the pancreaticobiliary maljunction where the pancreatic duct joined the bile duct, entering an approximately 2-cm-long common channel. Dilatation of the common bile duct and intrahepatic bile ducts was observed and diagnosed as the IV-A type according to the Toya classification. Abdominal angiography in the arterial phase showed dilatation of the cystic artery and hyperplasia of vessels but no apparent encasement. In the venous phase, a deep-staining tumor was observed. From the above findings, we made a diagnosis of gallbladder cancer complicating pancreaticobiliary maljunction, and performed an operation. Since intraoperative US showed that the outermost layer of the gallbladder was in part ill-demarcated, we diagnosed the depth of penetration as ss, and performed cholecystectomy and bile duct resection and hepatic resection (S4a and S5), and lymphnode dissection (D2; dissection of groups 1 and 2 lymphnodes). The resected specimen grossly showed a papillomatous lesion with a cauliflower-like surface. The histopathologic diagnosis was papillary adenocarcinoma, depth ss, stage II. Tumor cells proliferated in a papillomatous pattern and were mostly confined to the muscular coat but partly infiltrated into the subserosal coat. In the diagnosis of pancreaticobiliary maljunction, it is crucial to consider complicating gallbladder cancer.

[Usefulness of multi-lead electrocardiogram and transesophageal echocardiography for the detection and evaluation of intraoperative coronary spasm].

We describe a case of coronary spasm in a 59-year-old man undergoing an emergent abdominal aortic replacement for ruptured aortic aneurysm. The patient was brought to the operating room in a state of hypovolemic shock, and was successfully resuscitated through intensive volume expansion by rapid infusion devices. Twenty minutes after cross-clamping of the abdominal aorta, ST-segment elevation on the lead III of electrocardiogram (ECG) and dyskinesis in the inferior wall shown by transesophageal echocardiography (TEE) were noted. Coronary spasm was suspected, and isosorbide dinitrate was administered intravenously without delay, leading to prompt reversal of ischemic changes. A number of reports have suggested that care should be taken against coronary spasm in non-cardiac surgery as well as cardiac surgery, especially in patients with coronary risk factors. Monitoring by multi-lead ECG and TEE is a powerful method by which to detect and evaluate intraoperative myocardial ischemia.