Concurrent Nivolumab-Induced Gastritis and Cholangitis Accompanied by Biliary Tract Hemorrhage in a Patient With Stage IV Lung Adenocarcinoma.

Immune checkpoint inhibitors, including nivolumab, can result in immune-related adverse events (irAEs) that may affect multiple organ systems. Among irAEs, both gastritis and cholangitis are uncommon. We present the case of a 65-year-old man who received nivolumab for lung adenocarcinoma presented with epigastric pain. He was diagnosed with immune-related gastritis and cholangitis based on imaging and pathological findings. We administered prednisolone (1 mg/kg/day), which improved the patient's gastritis and relieved his pain. However, he experienced recurrent epigastric pain during corticosteroid tapering, and magnetic resonance imaging showed biliary tract hemorrhage. After watchful waiting, the hemorrhage improved without additional immunosuppressants. Immune-related gastritis, immune-related cholangitis, and their coexistence should be considered in patients who develop epigastric pain during immune checkpoint inhibitor therapy. When patients with concurrent immune-related gastritis and cholangitis complain of recurrent epigastric pain, it is important to assess which of these two irAEs is worsening because the optimal immunosuppressants differ between the two.

Efficacy of prompt administration of cryoprecipitate in severe postpartum hemorrhage of preeclampsia patients.

AIM: Cryoprecipitate (CRYO) is a concentrated preparation of coagulation factors formulated from fresh frozen plasma (FFP), which can replenish coagulation factors rapidly. Preeclampsia (PE) is frequently associated with postpartum hemorrhage (PPH), and the rapid replenishment of coagulation factors is vital in the management. We conducted a retrospective cohort study to determine the efficacy of administering CRYO irrespective of fibrinogen levels in patients with PE who experienced severe PPH. METHODS: Patients with PPH accompanied by PE and those who required red blood cell (RBC) transfusion were included. Cases were divided into two groups: those treated with CRYO (N = 16) and those not treated with CRYO (N = 10). The total transfusion volume, blood loss before and after transfusion initiation, duration of hospitalization, presence of pulmonary edema, and performance of either interventional radiology or hysterectomy were compared. RESULTS: The median fibrinogen levels before transfusion were 2.24 and 2.34 g/L in the CRYO group and the not using group, respectively. Although blood loss before transfusion was comparable between the two groups, blood loss after transfusion was significantly less in the CRYO group (median: 520 vs. 2352 mL, p = 0.015), as well as the total blood loss (median: 2285 vs. 3825 mL, p = 0.005) and total transfusion volume (median: RBC 6 vs. 16 U, p = 0.01, FFP 10 vs. 20 U, p = 0.017). CONCLUSION: Prompt replenishment of coagulation factors using CRYO to patients with PE who experience severe PPH could decrease further bleeding.

Clinical Feasibility of Completely Autologous Fibrin Glue in Spine Surgery.

Introduction: Fibrin glue is widely used in spine surgery. Nevertheless, no report has demonstrated the feasibility of completely autologous fibrin glue (CAFG) in spine surgery. This study aims to investigate the safety, efficacy, and effect of bone fusion of CAFG on spine surgery. Methods: We retrospectively extracted data of patients who underwent primary spine surgery with preoperatively prepared CAFG. Primary outcomes were the incidence of wound-related unplanned reoperations within 90 days following primary surgery and the occurrence of reoperation for the management of cerebrospinal fluid (CSF) leakage in patients who had been treated with CAFG used as dural sealants. The effect of CAFG on bone fusion was also assessed by detecting implant failure at one year postoperatively in patients aged 25 years or less undergoing primary fusion for idiopathic scoliosis. Results: We identified 131 eligible patients (47 males and 84 females) with a mean age of 32.3 years. CAFG was used most frequently as an adhesive for fixation of graft bone (110 patients), followed by as a dural sealant for CSF leakage in 17 patients, and as a local hemostatic agent in four patients. Wound-related reoperations were identified in four patients (3.1%), which included three for surgical site infection, and one for postoperative epidural hematoma. There was no reoperation required for the management of CSF leakage among 17 patients with dural incision or incidental durotomy. Compared with the control cohort, the use of CAFG was not associated with early wound-related reoperations or implant failure in patients with spinal deformity. Conclusions: We demonstrated the clinical feasibility of CAFG in spine surgery. The use of CAFG was not associated with the incidence of reoperations for wound-related complications. CAFG worked effectively as a dural sealant for preventing CSF leakage. CAFG had no beneficial or adverse effect on spinal bone fusion.

High-dose intravenous iron supplementation after preoperative autologous blood donation is useful to prevent post-donation/preoperative anemia.

To estimate the effectiveness of high-dose intravenous (IV) iron supplementation for iron deficiency anemia after preoperative autologous blood donation (PAD), 155 donors who visited the donation office of the University of Tokyo Hospital from December 2020 to June 2021 and showed suspected post-donation anemia were analyzed. The participants were treated with high-dose intravenous (IV) iron supplementation (high-dose group, n = 30) or a combination of low-dose IV iron and oral iron supplementation (low-dose group, n = 125). The preoperative hemoglobin (Hb) and Hb decreasing ratios during PAD (ΔHb) were compared between the two groups. Multivariate linear regression analyses were also performed to identify the confounding factors associated with preoperative Hb and ΔHb as well as high-dose IV iron supplementation. Preoperative Hb level was slightly higher in the high-dose group than in the low-dose group (12.1 ±â€¯1.1 vs. 11.9 ±â€¯1.1 g/dL, p = 0.27). ΔHb was significantly higher in the high-dose group than in the low-dose group (3.7 % ± 8.8 % vs. 7.7 % ± 6.5 %, p = 0.011). On the multivariate linear regression analyses, high-dose IV iron supplementation was significantly associated with higher preoperative Hb and lower ΔHb levels (p = 0.021 and 0.017, respectively) as well as the donation available period (period from the first visit to the donation office to the operation) and administration of erythropoiesis-stimulating agents. High-dose IV iron supplementation after PAD will be useful in the treatment of post-donation anemia.

Cardiac Variation of Internal Jugular Vein as a Marker of Volume Change in Hemorrhagic Shock.

BACKGROUND: Fluid resuscitation, which is critical to counter acute hemorrhagic shock, requires prompt and accurate intravascular volume estimation for optimal fluid administration. This study aimed to evaluate whether cardiac variation of internal jugular vein (IJV), evaluated by ultrasonography, could detect hypovolemic status and predict response to fluid resuscitation. METHODS: Patients undergoing autologous blood transfusion for elective surgery who were prospectively enrolled at the study blood donation center between August 2014 and January 2015. Vertical B-mode ultrasonography movies of IJV were recorded at five timepoints during blood donation: before donation, during donation, end of donation, end of fluid replacement, and after hemostasis. Cardiac variation of the IJV area and circumference were objectively measured using an automated extraction program together with blood pressure and heart rate. RESULTS: A total of 140 patients were screened, and data from 104 patients were included in the final analyses. Among the variables analyzed, only collapse index area and collapse index circumference could detect both intravascular volume loss and response to fluid administration. CONCLUSIONS: Cardiac variation of IJV may be a reliable indicator of intravascular volume loss and response to fluid administration in hemorrhagic shock.

Comparison of two point of care whole blood coagulation analysis devices and conventional coagulation tests as a predicting tool of perioperative bleeding in adult cardiac surgery-a pilot prospective observational study in Japan.

BACKGROUND: It is widely accepted that Point-of Care Test (PoCT) devices are useful in the detection of coagulopathies in situations of massive bleeding such as major cardiac surgery. These devices contribute to the reduction of blood transfusion. However, their implementation remains limited in Japan because of their cost and lack of health insurance support. STUDY DESIGN AND METHODS: Conventional coagulation tests and thromboelastography (TEG)/Sonoclot values were measured in 50 consecutive cardiac surgery cases. Clinical background information such as operative procedures was obtained from electronic medical records, and the theoretical perioperative total blood loss was calculated by measuring the hemoglobin content and total red blood cell transfusion volume. The correlation between perioperative total blood loss and the measured laboratory values or clinical parameters was evaluated by a multivariate linear regression analysis. The risk factors of the total amount of platelet transfusion and postoperative drain bleeding volume were similarly evaluated. RESULTS: No significant association between the estimated perioperative total blood loss (eTBL) and the laboratory measurements including conventional coagulation tests, TEG and Sonoclot was observed. On the other hand, postoperative drain bleeding volume was significantly associated with postoperative Sonoclot CR (p = 0.039) as well as preoperative use of oral anticoagulants and cell saver treated blood volume. Platelet transfusion amount was significantly associated with post-CBP PF and time to peak value of Sonoclot (p = 0.014 and 0.001, respectively). CONCLUSION: Sonoclot measurements may be useful to estimate the risks of postoperative bleeding and platelet transfusion in cardiac surgeries in Japan.

Separation between the chest wall and subpleural lung lesions: A two-step method to preoperatively exclude invasion or focal pleural adhesion by multidetector computed tomography.

PURPOSE: To develop and assess a non-invasive two-step method for evaluating the relationship between the parietal pleura and peripheral pulmonary lesions to preoperatively exclude invasion or focal pleural adhesion by multidetector computed tomography (CT). METHODS: Twenty-six patients with pulmonary peripheral lesions who underwent surgical lung resection between May and December 2017 were enrolled in this study. Routine CT was performed in the inspiratory phase in the supine position. Additional CT examinations were performed both in inspiratory and expiratory phases in the affected-side-up lateral position. Axial, sagittal, and coronal images were reconstructed from the CT data. In the first-step analysis, we evaluated the separation between the chest wall and subpleural lung lesions (separation) by comparing inspiratory- and expiratory-phase images obtained in the affected-side-up lateral position. When the separation was absent, we performed a second-step analysis, where we compared images obtained in the supine position during routine CT with those obtained in the affected-side-up lateral position and subsequently assessed the presence and absence of the separation. RESULTS: In the first-step analysis, the separation was observed in 21 lesions, which were categorised as showing "no invasion" or "no focal adhesion" on the basis of histological findings. After the second-step analysis, the separation was absent in three lesions and present in two; the latter two lesions were categorised as showing "no invasion" or "no focal adhesion" on the basis of operative and histological findings. Of the three lesions that did not exhibit the separation in either step of the analysis, two were diagnosed as exhibiting parietal pleural invasion on the basis of histological findings, while the third was categorised as showing "no invasion" or "no focal adhesion" on the basis of operative and histological findings. The sensitivity, specificity, positive and negative predictive values, and accuracy of this two-step method were 96% (95% confidence interval [CI]: 79-100%), 100% (95% CI: 16-100%), 100%, 67% (95% CI: 23-93%), and 96% (95% CI: 80-100%), respectively. CONCLUSIONS: Our two-step method is especially useful for excluding the parietal pleural involvement of peripheral pulmonary lesions. Even when the separation between the chest wall and subpleural lung lesions was limited, the change in position was useful for observing the separation and excluding parietal pleural involvement. This novel two-step method also has the advantage of being simple, cost-effective, and universally available.

Pilot study on novel blood containers with alternative plasticizers for red cell concentrate storage.

Di (2-ethylhexyl) phthalate (DEHP), a typical plasticizer used for polyvinyl chloride (PVC) blood containers, is eluted from the blood containers and exerts protective effects on red blood cells. However, a concern for detrimental effects of DEHP on human health has led to the development of potential DEHP substitutes. Here, we compared the red blood cell preservation ability of two types of non-DEHP blood containers with safe alternative plasticizers to that of DEHP blood containers. Red cell concentrates in mannitol-adenine-phosphate solution (MAP/RCC) were stored for 6 weeks in PVC blood bags containing DEHP, di-isononyl-cyclohexane-1,2-dicarboxylate (DINCH) and di (2-ethylhexyl) 4-cyclohexene-1,2-dicarboxylate (DOTH), or 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester (DL9TH) and DOTH. There was no significant difference in the total amount of plasticizer eluted into MAP/RCC (till 3 weeks from the beginning of the experiment), hemolysis of MAP/RCC, and osmotic fragility of MAP/RCC between the non-DEHP blood containers and DEHP blood containers. Hematological and blood chemical indices of MAP/RCC in all containers were nearly the same. Thus, DOTH/DINCH and DOTH/DL9TH blood containers demonstrate the same quality of MAP/RCC storing as the DEHP blood containers. Since DOTH, DINCH, and DL9TH were reported to be safe, DOTH/DINCH and DOTH/DL9TH blood containers are promising candidate substitutes for DEHP blood containers.

Targeting gene expression to specific cells of kidney tubules in vivo, using adenoviral promoter fragments.

Although techniques for cell-specific gene expression via viral transfer have advanced, many challenges (e.g., viral vector design, transduction of genes into specific target cells) still remain. We investigated a novel, simple methodology for using adenovirus transfer to target specific cells of the kidney tubules for the expression of exogenous proteins. We selected genes encoding sodium-dependent phosphate transporter type 2a (NPT2a) in the proximal tubule, sodium-potassium-2-chloride cotransporter (NKCC2) in the thick ascending limb of Henle (TALH), and aquaporin 2 (AQP2) in the collecting duct. The promoters of the three genes were linked to a GFP-coding fragment, the final constructs were then incorporated into an adenovirus vector, and this was then used to generate gene-manipulated viruses. After flushing circulating blood, viruses were directly injected into the renal arteries of rats and were allowed to site-specifically expression in tubule cells, and rats were then euthanized to obtain kidney tissues for immunohistochemistry. Double staining with adenovirus-derived EGFP and endogenous proteins were examined to verify orthotopic expression, i.e. "adenovirus driven NPT2a-EGFP and endogenous NHE3 protein", "adenovirus driven NKCC2-EGFP and endogenous NKCC2 protein" and "adenovirus driven AQP2-EGFP and endogenous AQP2 protein". Owing to a lack of finding good working anti-NPT2a antibody, an antibody against a different protein (sodium-hydrogen exchanger 3 or NHE3) that is also specifically expressed in the proximal tubule was used. Kidney structures were well-preserved, and other organ tissues did not show EGFP staining. Our gene transfer method is easier than using genetically engineered animals, and it confers the advantage of allowing the manipulation of gene transfer after birth. This is the first method to successfully target gene expression to specific cells in the kidney tubules. This study may serve as the first step for safe and effective gene therapy in the kidney tubule diseases.

Isolated unilateral proximal interruption of the pulmonary artery: findings of high-resolution computed tomography and three-dimensional volume rendering imaging of the pleura.

A unilateral proximal interruption of the pulmonary artery is a rare entity that is commonly associated with other congenital cardiovascular anomalies. However, less frequently, this condition may occur as an isolated finding, and some patients are completely asymptomatic. We report 2 cases of asymptomatic patients who had an isolated unilateral proximal interruption of the pulmonary artery. Herein, the radiological imaging findings are described with an emphasis on interlobular septal thickening of the affected lung demonstrated with high-resolution computed tomography. Three-dimensional volume rendering imaging clearly demonstrated reticular opacities on the surface of the affected side of the pleura.

[Subtotal Esophagectomy for Mediastinal Lymph Node Oligo-Recurrence of ALK-Positive Lung Adenocarcinoma - A Case Report].

The patient was a 54-year-old woman with anaplastic lymphoma kinase-positive stage III B lung cancer. She received 4 courses of carboplatin(CBDCA)plus paclitaxel(PTX)plus bevacizumab(Bev)chemotherapy and crizotinib. Chemotherapy reduced the size of the primary site and mediastinal lymphadenopathy; however, the right supraclavicular and subcarinal lymph nodes were enlarged again during crizotinib treatment. Because it was an oligo-recurrence, we performed radiotherapy for these lymph nodes and changed systemic chemotherapy to alectinib. After 16 months, the patient exhibited esophageal stenosis due to subcarinal lymphadenopathy. We performed a subtotal esophagectomy, which improved the quality of life, and she was continued on an oral treatment of alectinib. Therefore, we suggest that an invasive surgical treatment is useful for oligo-recurrence cases.

Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63.

OBJECTIVE: Transcription factor p63, of the p53 family, regulates cell proliferation, survival, and apoptosis in various cells and tissues. This study was undertaken to examine the expression and roles of p63 transcript variants in the mouse growth plate and articular chondrocytes. METHODS: For in vivo analyses, we generated Cre-mediated TAp63α-transgenic and TAp63γ-transgenic mice. To induce tissue-specific overexpression or deletion in chondrocytes, chondroprogenitor cells, or early limb bud mesenchymal cells, we used Col2a1-Cre, Sox9-Cre, and Prx1-Cre mice, respectively. We analyzed osteoarthritis (OA) development with aging or surgically induced instability in Prx1-Cre;p63fl/fl (P-conditional knockout) mice. RESULTS: Among major variants, TAp63α and TAp63γ are highly expressed in mouse primary costal and articular chondrocytes. The p63 protein was predominantly localized in the hypertrophic zone of the embryonic limb cartilage, and in the middle zone of articular cartilage. No obvious change was observed in skeletal growth of TAp63α-transgenic mice, Sox9-Cre;p63fl/fl , or P-conditional knockout mice, while that of TAp63γ-transgenic mice was impaired due to ectopic apoptosis and the resulting decreased number of chondrocytes. Expression of proapoptotic genes including bax, noxa, puma, and fas was increased in TAp63γ-transgenic mouse chondrocytes, and their transcription was probably sustained by p53 in p63-conditional knockout mouse chondrocytes because both proteins were coexpressed in the growth plate. In contrast, p53 was expressed in the superficial zone of articular cartilage, differently from p63. Notably, P-conditional knockout mice showed significant resistance to OA development, with suppression of chondrocyte apoptosis in the aging and surgical models. CONCLUSION: We demonstrated regulation of chondrocyte survival in articular cartilage by p63.

Dicephalus Parapagus Conjoined Twins Diagnosed by First-Trimester Ultrasound.

Conjoined twins are a rare phenomenon, occurring in 1% of monochorionic twin gestation, with an incidence of 1 : 50 000 to 1 : 100 000. Many conjoined twins have abnormalities incompatible with life, so early prenatal diagnosis is very important for optimal management of both pregnancy and delivery. We report a case of dicephalus parapagus conjoined twins, sharing a single heart, diagnosed at 12 weeks' gestation. With early ultrasound diagnosis, we were able to provide appropriate and timely prenatal counseling to the family.

Clinical Features of Miller-Fisher Syndrome in Pregnancy.

Miller-Fisher syndrome (MFS) is recognized as a variant of Guillain-Barré syndrome (GBS). MFS is a rare disorder that is characterized by the acute onset of ophthalmoplegia, ataxia, and areflexia/hyporeflexia. MFS has a higher incidence in Asia, where the incidence is estimated to be 18%-26% of GBS compared with 3%-5% in the West. The differential diagnosis of MFS includes Wernicke's encephalopathy (WE) which is characterized by a clinical triad (nystagmus and ophthalmoplegia, mental status changes, and ataxia), myasthenia gravis, and brainstem stroke. The association between MFS and pregnancy has not been reported previously. Here, we describe the clinical features of a pregnant woman in early pregnancy with MFS. This case highlights the fact that it is necessary to establish an accurate diagnosis based on the details from the patient's history on appropriate complementary testing in a pregnant patient with MFS.

A Rare Case of Meconium Periorchitis Diagnosed in Utero.

Meconium periorchitis is a rare disorder caused by fetal meconium peritonitis, with subsequent passage of meconium into the scrotum via a patent processus vaginalis. To date, clinical significance of meconium periorchitis for the prenatal diagnosis of meconium peritonitis and prediction for postnatal surgery remains to be determined. We present a clinical course of a fetus presenting with meconium periorchitis induced by meconium peritonitis. At 28 weeks' gestation, fetal ultrasonography indicated fetal ascites associated with bilateral hydrocele and peritesticular calcification without other signs of meconium peritonitis. The pregnancy was uneventful until delivery and the infant was delivered at 37 weeks' gestation. No abdominal distension was observed at birth, and radiography did not reveal any abdominal calcification except for scrotal calcification. Abdominal distension was observed 3 days after birth and laparotomy was performed. The diagnosis of meconium peritonitis was confirmed at surgery. Our case illustrated that careful examination of the scrotum during fetal life was helpful for prenatal diagnosis of meconium peritonitis as well as postnatal management.