Clinical and Genetic Characteristics of Early and Advanced Gastric Cancer.

Gastric cancer (GC) persists as the fourth most prevalent cause of global cancer-related mortality, presenting a challenge due to the scarcity of available therapeutic strategies. Precision medicine is crucial not only in the treatment but also in the management of GC. We performed gene panel sequencing with Oncomine focus assay comprising 52 cancer-associated genes and MSI analysis in 100 case-matched gastric cancer cases. A comprehensive analysis of clinical and genetic characteristics was conducted on these genetic results and clinicopathological findings. Upon comparison of clinicopathological characteristics, significant differences between early gastric cancer (EGC) and advanced gastric cancer (AGC) were observed in tumor location (p = 0.003), Lauren classification (p = 0.015), T stage (p = 0.000), and N stage (p = 0.015). The six most frequently mutated genes were PIK3CA (29%, 10/35), ERBB2 (17%, 6/35), KRAS (14%, 5/35), ALK (6%, 2/35), ESR1 (6%, 2/35), and FGFR3 (6%, 2/35). Regarding genetic variation, there was a tendency for the N stage to be higher in GC patients with mutated genes (p = 0.014). The frequency of mutations in GC patients was statistically significantly higher in AGC (n = 24) compared to EGC (n = 11) (odds ratio, 2.792; 95% confidence interval, 1.113 to 7.007; p = 0.026). Six of the ten GC patients carrying mutated genes and exhibiting MSI were classified into intestinal-type and undifferentiated GC, with the location of the tumor being in the lower-third. Among these patients, five harbored mutated PIK3CA, while the remaining patient had a mutation in ALK. Conclusions: AGC patients more frequently exhibited alterations of PIK3CA, KRAS, and ERBB2 as somatic oncogenic drivers, and displayed a higher prevalence of cumulative genetic events, including increased rates of PIK3CA mutations, enhanced detection of immunotherapy biomarkers, and mutations of the ESR1 gene.

Spontaneous splenic rupture associated with scrub typhus: a case report.

BACKGROUND: Scrub typhus, an acute febrile disease with mild to severe, life-threatening manifestations, potentially presents with a variety of complications, including pneumonia, acute respiratory distress syndrome, cardiac arrhythmias (such as atrial fibrillation), myocarditis, shock, peptic ulcer, gastrointestinal bleeding, meningitis, encephalitis, and renal failure. Of the various complications associated with scrub typhus, splenic rupture has rarely been reported, and its mechanisms are unknown. This study reports a case of scrub typhus-related spontaneous splenic rupture and identifies possible mechanisms through the gross and histopathologic findings. CASE PRESENTATION: A 78-year-old man presented to our emergency room with a 5-day history of fever and skin rash. On physical examination, eschar was observed on the left upper abdominal quadrant. The abdomen was not tender, and there was no history of trauma. The Orientia tsutsugamushi antibody titer using the indirect immunofluorescent antibody test was 1:640. On Day 6 of hospitalization, he complained of sudden-onset left upper abdominal quadrant pain and showed mental changes. His vital signs were a blood pressure of 70/40 mmHg, a heart rate pf 140 beats per min, and a respiratory rate of 20 breaths per min, with a temperature of 36.8 °C. There were no signs of gastrointestinal bleeding, such as hematemesis, melena, or hematochezia. Grey Turner's sign was suspected during an abdominal examination. Portable ultrasonography showed retroperitoneal bleeding, so an emergency exploratory laparotomy was performed, leading to a diagnosis of hemoperitoneum due to splenic rupture and a splenectomy. The patient had been taking oral doxycycline (100 mg twice daily) for 6 days; after surgery, this was discontinued, and intravenous azithromycin (500 mg daily) was administered. No arrhythmia associated with azithromycin was observed. However, renal failure with hemodialysis, persistent hyperbilirubinemia, and multiorgan failure occurred. The patient did not recover and died on the fifty-sixth day of hospitalization. CONCLUSIONS: Clinicians should consider the possibility of splenic rupture in patients with scrub typhus who display sudden-onset abdominal pain and unstable vital signs. In addition, splenic capsular rupture and extra-capsular hemorrhage are thought to be caused by splenomegaly and capsular distention resulting from red blood cell congestion in the red pulp destroying the splenic sinus.

Dual outflow upper arm arteriovenous fistula: An effective technique to prevent cephalic arch stenosis.

Cephalic arch stenosis (CAS) is critical point to maintain functional arteriovenous fistula (AVF) in patients undergoing hemodialysis with brachio-cephalic AVFs. In this study, we aimed to determine the effectiveness of dual outflow (cephalic and basilic veins) as a surgical method to prevent CAS. Between July 2016 and December 2019, 369 patients underwent upper arm AVF creation. Among them the 251 patients were enrolled in this retrospective study. Two hundred seven underwent brachio-cephalic arteriovenous fistula (BCAVF) and 44 underwent brachio-cephalicbasilic arteriovenous fistula (BCBAVF). From the 251 patients, diabetes mellitus (66.7% vs 36.4%, P < .001) and hypertension (91.3% vs 75%, P = .002) were more common in the patient group who underwent BCAVF surgery; however, the difference in volume flow to the fistula did not differ between the 2 groups. CAS (30.4% vs 9.1%, P = .004) and fistula occlusion (15.9% vs 4.5%, P = .048) were likely to occur in the BCAVF group. The primary patency rates at 12 months were 74.3% and 86.4% for the BCAVFs and BCBAVFs, respectively (P = .075). The primary-assisted patency rates at 12 months were 87.0% for BCAVFs and 93.2% for BCBAVFs, respectively (P = .145). Secondary patency rates at 12 months were 92.2% for BCAVFs and 93.2% for BCBAVFs, respectively (P = .023). Compared to BCAVF, traditional upper arm AVF, upper arm AVF with cephalic and basilic vein dual drainage can be optimal surgical method to preventing CAS.

Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation.

Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.

Graft lymphoma in a kidney transplant recipient: a case report.

Posttransplant lymphoproliferative disorders (PTLDs) are severe complications with heterogeneous clinical pictures involving abnormal lymphoproliferation in solid organ transplants and are known to be closely associated with Epstein-Barr virus (EBV) infection. Herein, we present a case of graft lymphoma in a febrile kidney transplant recipient. A 37-year-old woman was admitted with an abrupt 39 °C fever, mild graft discomfort, and gross hematuria. She had received deceased donor kidney transplantation 8 years earlier, but developed graft failure due to a recurrence of immunoglobulin A nephropathy. Laboratory tests revealed anemia and elevated levels of inflammatory markers. Enhanced abdominopelvic computed tomography showed graft swelling with perirenal fat stranding. Thus, we administered antibiotics for a urinary tract infection and increased the doses of steroids due to suspicion of graft intolerance syndrome. However, the patient's symptoms gradually worsened. Eventually, we performed graft nephrectomy and histologically confirmed EBV-positive diffuse large B cell lymphoma. We report a case in which a PTLD was considered in the differential diagnosis of a kidney transplant recipient with symptoms similar to those of a urinary tract infection or graft intolerance syndrome.

Denali Inferior Vena Cava Filter Retrieval: Complications and Success Rates.

Purpose: The present study was to evaluate the outcomes of Denali filter retrieval. Materials and Methods: We retrospectively reviewed 143 patients who received Denali filter insertion from September 2015 to April 2020. Ninety-seven patients who required removal of the filters were include in this study. Filters were retrieved with either standard or advanced techniques. Venography before and after retrieval was obtained to evaluate technical success, complications and duration of filter insertion. Results: All 97 filters were retrieved successfully without complications. Ninety-two (94.8%) were retrieved with standard technique and 5 filters (5.2%) required the advanced technique. There were two cases with a filter angle greater than 15 degrees. Inferior vena cava penetration was shown in 17 patients (17.5%) on venography but was not associated with contrast media extravasation after filter removal. Conclusion: The Denali filter showed a high rate of successful retrieval without complications. This study adds value to previous studies and trials showing that the Denali filter is a reliable and safe filter that can potentially improve retrieval rates, with increasing use of this device.

Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report.

BACKGROUND: The coinfection between cytomegalovirus (CMV) and either human herpesvirus-6 (HHV-6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV-8 coinfection after renal transplantation. CASE PRESENTATION: A 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi's sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved. CONCLUSIONS: We report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.

Prospective, Multicenter Study of Rotational Atherectomy with Antirestenotic Therapy for Infrainguinal Arterial Disease.

BACKGROUND: Thrombi are common in steno-occlusive lesions of infrainguinal atherosclerotic diseases. Despite the easy passage of guidewires through these lesions, conventional ballooning or stenting cannot effectively treat them, and patients are at risk of distal embolization. This study aimed to investigate the clinical outcomes of using a rotational aspiration atherectomy system to treat infrainguinal atherosclerotic disease. METHODS: Patients underwent revascularization of target lesions using the Jetstream™ Atherectomy System. The primary endpoint was the freedom from clinically driven target lesion revascularization (CD-TLR) 12-month after the procedure. Outcomes were evaluated according to the clinical severity, lesion type, use of drug-coated balloons (DCBs), and lesion length, characteristics, and sites. Survival analysis for CD-TLR over time was plotted. All statistical analyses were performed using SPSS version 22 (IBM; Armonk, NY, USA). P-values <0.05 were considered statistically significant. RESULTS: In total, 150 patients (91.2% male; mean age, 69.8 years; 66.2% with diabetes) with de novo or restenotic infrainguinal lesions were enrolled. The mean lesion length was 17.2 cm, 75.0% were occlusive, and 38.2% had severe calcification. The lesion types were sclerotic (64.7%), thrombosclerotic (20.6%), thrombotic (8.8%), and in-stent (5.9%). Adjunctive DCB was used in 86.8% of patients. The 12-month primary patency rate (PPR) and CD-TLR rates were 81.6% and 90.1%, respectively. The 12-month CD-TLR rate was significantly better in the sclerotic and thrombosclerotic groups than in the thrombotic group (100% and 100% vs. 66.7%; P = 0.001). The 12-month PPR was significant better in TransAtlantic Inter-Society Consensus (TASC) A and B groups than TASC C and D groups (P = 0.02). The 12-month PPR is significantly better after using a DCB or stent placement than after using a simple balloon (P = 0.01). There were no major adverse events, including procedure-related death, myocardial infarction, or major amputation. CONCLUSIONS: The results of this study demonstrated the safety and effectiveness of the Jetstream atherectomy device for complex infrainguinal lesions. This system functions optimally with TASC A/B lesions and sclerotic or thrombosclerotic lesions.

Open Sciatic Nerve Decompression for Compartment Syndrome after Prolonged Lithotomy Position: A Case Report.

Background: Position-related compressive nerve injury is a frequently reported complication of the lithotomy position. In contrast, compartment syndrome-induced neuropathy after lithotomy with prolonged surgery is rare and prone to misdiagnosis. This case describes the successful open decompression of sciatic neuropathy due to compartment syndrome after a prolonged lithotomy position. Case presentation: A 56-year-old male patient complained of an abnormal sensation in the lower leg and difficulty in dorsiflexion and plantarflexion of the left foot and toes after laparoscopic anterior hepatic sectionectomy for 16 h in a lithotomy position. Physical examination revealed severe pain and paresthesia below the distal left thigh. In manual muscle test grading, dorsiflexion and plantarflexion of the left ankle and toes were classified as grade 1. Computed tomography and magnetic resonance imaging showed ischemic changes in the mid-thigh posterior muscles, and the sciatic nerve was severely swollen at the distal thigh, which was compressed by the proximal edge of the well-leg holder. After debridement of the necrotic tissue and decompression of the sciatic nerve, the pain subsided immediately, and the ankle and toe dorsiflexion motor function improved to grade 4. Conclusions: Most case reports of compressive neuropathy associated with the lithotomy position have been related to conservative treatment. However, if a lesion compressing the nerve is confirmed in an imaging study and the correlation with the patient's symptoms is evident, early surgical intervention can be an effective treatment method to minimize neurological deficits.

Delayed pseudoaneurysm formation of the carotid artery following the oral cavity injury in a child: A case report.

BACKGROUND: An impalement injury of the oral cavity is a common traumatic injury in children. In most cases, it is not accompanied by sequelae, but if foreign body residues are not found due to a minor injury, they may result in inflammatory responses and delayed vascular injuries in the surrounding tissues. Without early diagnosis and appropriate initial management, residual foreign bodies can cause serious complications and even mortality in some cases. CASE SUMMARY: A 9-year-old boy suffered an intra-oral injury by a wooden chopstick, and the patient was discharged from the hospital after receiving conservative treatment for the injury. However, the patient was readmitted to the hospital due to intra-oral bleeding, and since neck hematoma and right internal carotid artery pseudoaneurysm formation were detected on computed tomography, emergency surgery was performed. A remnant fragment of a wooden chopstick was found during the operation, and a delayed rupture of the internal carotid artery caused by the foreign body was also found. CONCLUSION: The failure of early detection and diagnosis of a residual foreign body may result in delayed vascular rupture.

Laparoscopic lumbar artery ligation of type II endoleaks following endovascular aneurysm repair: A case report.

INTRODUCTION: Although the clinical significance of type II endoleaks remain controversial, management strategies continue to expand. The laparoscopic approach is a minimally invasive method for persistent type II endoleak repair after endovascular aneurysm repair. PATIENT CONCERNS: A 70 - year - old male patient with a history of endovascular aneurysm repair with left internal iliac artery embolization presented with persistent type II endoleak from the lumbar arteries 2 years ago. The aneurysm sac size had increased more than 10 mm during follow up period. DIAGNOSIS: Persistent type II endoleak after endovascular aneurysm repair. INTERVENTIONS: Transarterial embolization was attempted and failed. A minimally invasive laparoscopic lumbar artery ligation was then utilized. OUTCOMES: The patient was discharged without any complications after surgery. Follow-up computed tomography angiography has shown the complete disappearance of the type II endoleaks. CONCLUSIONS: Laparoscopic lumbar artery ligation may be a safe and effective alternative treatment for type II endoleaks, especially in high resource settings.

Comparison of diffusion-weighted imaging and MR elastography in staging liver fibrosis: a meta-analysis.

PURPOSE: To compare the diagnostic performance of diffusion-weighted imaging (DWI), gradient-recalled echo-based magnetic resonance elastography (GRE-MRE), and spin-echo echo-planar imaging-based MRE (SE-EPI-MRE) in liver fibrosis staging. METHODS: A systematic literature search was done to collect studies on the performance of DWI, GRE-MRE, and SE-EPI-MRE for diagnosing liver fibrosis. Pooled sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratio, and a summary receiver operating characteristic (ROC) curve were estimated with a bivariate random effects model. Subgroup analyses on various study characteristics were performed. RESULTS: Sixty studies with a total of 6620 patients were included in the meta-analysis. Pooled sensitivity and specificity of GRE-MRE and SE-EPI-MRE showed high diagnostic accuracy and did not differ significantly. The area under the summary ROC curve for all stages of fibrosis differed significantly between DWI (0.83-0.88) and either GRE-MRE (0.95-0.97) or SE-EPI-MRE (0.95-0.99). Substantial heterogeneity was detected for all three imaging methods. CONCLUSIONS: Both GRE-MRE and SE-EPI-MRE are highly accurate for detection of each liver fibrosis stage, with high potential to replace liver biopsy. Although DWI had a moderate accuracy in distinguishing liver fibrosis, it could be regarded as an alternative to MRE, since it is widely available and easily implemented in routine liver MRI.

Severe anorexia and weight loss induced by tacrolimus in kidney transplant recipients.

Common neuropsychiatric complications of tacrolimus include tremors, fatigue, headache, sleep disorders, paranoid reactions, and anxiety. Other, more serious complications include encephalopathy, convulsions, confusion, and coma. To our knowledge, however, severe weight loss by anorexia has not been reported as a neuropsychiatric adverse effect of tacrolimus given to adult kidney transplant recipients. In this article we present two cases of severe anorexia and weight loss associated with tacrolimus that appeared to reverse with cyclosporine.

Myositis ossificans of the thigh causing external compression of the superficial femoral artery and vein: A case report.

RATIONALE: Myositis ossificans (MO) is a benign condition characterized by heterotopic bone formation in the skeletal muscle of extremities. Marked variation can occur in the incidence and location of the bone formed as well as resulting complications. Femoral vessel obstruction caused by MO is an extremely rare but disabling complication. Arterial occlusion may aggravate ischemic conditions, resulting in necrosis in the lower extremity. PATIENT CONCERNS: We report a 41-year-old female with progressive pain and swelling of the right thigh region for 1 year. DIAGNOSES: We diagnosed it as obstruction of the superficial femoral artery and vein caused by external compression of the MO between the sartorius and vastus medialis of the thigh. INTERVENTIONS AND OUTCOMES: Adherent tissues and mass were excised with care without damaging the femoral artery or the vein. However, normal morphology did not recover due to loss of elasticity of femoral vessels. Therefore, after resection of the narrowed region of the femoral artery, a femoral-to-femoral graft interposition using the greater saphenous vein was performed. At 12 months after the surgery, vessel reconstruction computed tomography images confirmed normal continuous flow of the femoral artery. LESSONS: Vascular compression and peripheral inflammatory response due to MO can cause loss of normal vascular morphology. Surgical excision of the mass and the involved femoral artery segment followed by femoral arterial reconstruction should be considered for lesions that do not spontaneously regress to prevent functional impairment and secondary complications in extremities.

Factors Affecting Recurrent Deep Vein Thrombosis after Pharmacomechanical Thrombolysis and Left Iliac Vein Stent Placement in Patients with Iliac Vein Compression Syndrome.

PURPOSE: This study evaluated the factors affecting contralateral and ipsilateral recurrent deep vein thrombosis (DVT) after iliac vein stent placement in patients with iliac vein compression syndrome (IVCS). MATERIALS AND METHODS: Data from 130 patients (95 female patients) who underwent catheter-directed thrombolysis and stent placement for IVCS with left lower leg thrombosis at a single institution were retrospectively analyzed. Mean patient age was 69.0 ± 14.0 years old. Median follow-up was 14 months (range, 3-164 months). Anticoagulation therapy was prescribed for 6 months, followed by lifelong antiplatelet therapy. Multivariate logistic regression analysis was performed to evaluate the factors affecting the development of contralateral and ipsilateral recurrent DVT. RESULTS: Seven patients (5.4%) developed contralateral DVT (median, 26 months; range, 2-61 months), and 11 patients (8.5%) developed ipsilateral DVT (median, 1 month; range, 0-53 months). Stent location (odds ratio [OR], 11.564; 95% confidence interval [CI], 1.159-115.417) and in-stent thrombosis during follow-up (OR, 15.142; 95% CI, 1.406-163.119) were predictors of recurrent contralateral DVT. Thrombophilia (OR, 47.560; 95% CI, 2.369-954.711), remaining inferior vena cava filter (OR, 30.552; 95% CI, 3.495-267.122), and in-stent thrombosis during follow-up (OR, 82.057; 95% CI, 2.915-2309.848) were predictors of ipsilateral DVT. CONCLUSIONS: Contralateral DVT occurs late and is associated with extension of the iliac vein stent to the inferior vena cava and in-stent thrombosis. Ipsilateral DVT occurs relatively early and is associated with thrombophilia, remaining inferior vena cava filter, and in-stent thrombosis.

Organ procurement in a deceased donor.

With the increasing demand for organ transplantation, organ procurement from a deceased donor is an essential step for deceased donor organ transplantation. A proper surgical technique for the procurement of an organ graft from a deceased donor must be carried out to avoid any damage to it. Moreover, how to manage deceased donors until they enter the operating room in a stable condition is a critical point to be considered. The establishment of a surgical technique and preoperative management for organ procurement is encouraged to achieve a nationwide standard and consistency for organ graft sharing among the transplant units.

The Degree of Hyperglycemia Excursion in Patients of Kidney Transplantation (KT) or Liver Transplantation (LT) Assessed by Continuous Glucose Monitoring (CGM): Pilot Study.

OBJECTIVE: This study used a continuous glucose monitoring system (CGMS) to investigate the glucose profiles and assess the degree of hyperglycemic excursion after kidney or liver transplantation during the early period after operation. METHODS: Patients to whom a CGMS was attached during a postoperative period of approximately one month after transplantation were included. The CGM data of 31 patients including 24 with kidney transplantation (KT) and seven with liver transplantation (LT) were analyzed. RESULTS: Hyperglycemia over 126 mg/dL (fasting) or 200 g/dL (postprandial) occurred in 42.1% (8/19) and 16.7% (1/6) of KT and LT patients, respectively, during this early period after transplantation, except for patients with preexisting diabetes (5 KT, 1 LT). The average mean amplitude of glycemic excursion (MAGE) and mean absolute glucose (MAG) levels were 91.18 ± 26.51 vs. 65.66 ± 22.55 (P < 0.05) and 24.62 ± 7.78 vs. 18.18 ± 7.07 (P < 0.05) in KT vs. LT patients, respectively, in patients without preexisting DM or PTDM patients who showed normal glucose levels. Average increase from the lowest level to the peak glucose value was higher in KT patients than LT patients (P < 0.05). Conclusions. The transplanted organ also needs to be considered as an important factor affecting glucose control and the occurrence of more severe glucose excursions in patients who receive transplantation although immunosuppression agents are well-known important factors; however, our study was limited to the early posttransplantation period. Further studies involving CGM follow-up at regular intervals based on the time since transplantation are needed.

Liver Fibrosis Assessment with Diffusion-Weighted Imaging: Value of Liver Apparent Diffusion Coefficient Normalization Using the Spleen as a Reference Organ.

Liver fibrosis staging is of great clinical importance because it is used to assess the severity of the underlying chronic liver disease. Among various imaging-based methods, apparent diffusion coefficient (ADC) measurement using diffusion-weighted imaging (DWI) has the potential to be used as an imaging biomarker for liver fibrosis assessment. In this study, we investigated the usefulness of liver ADC normalization using the spleen as a reference organ in liver fibrosis staging with 66 patients who underwent liver magnetic resonance imaging (MRI), transient elastography (TE), and surgical resection of a hepatic mass. ADC values of the liver (ADCliver) and spleen were analyzed, and the spleen was used for ADCliver normalization (nADCliver). ADCliver showed a weak negative correlation with TE (r = -0.246; p = 0.047) and fibrosis stage (r = -0.269; p = 0.029), while n ADCliver showed a moderate negative correlation with TE (r = -0.504; p < 0.001) and fibrosis stage (r = -0.579; p < 0.001). AUC values for nADCliver (0.777-0.875) were higher than those for ADCliver for each stage of fibrosis (0.596-0.713, p = 0.037-0.157). AUC values for TE (0.726-0.884) and nADCliver were not statistically different. In conclusion, normalized liver ADC can be useful in diagnosing liver fibrosis stage in patients with variable DWI acquisitions.

Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans.

Adipose tissue inflammation is a reproducible feature of obesity and obesity-linked insulin resistance. Although sirtuin 6 (Sirt6) deficiency has previously been implicated in diet-induced obesity and systemic insulin resistance, the adipocyte-specific role of Sirt6 in the regulation of adipose tissue inflammation and systemic metabolic dysfunction in mice fed normal chow and in humans remains elusive. Here, using Adipoq-Cre-mediated adipocyte-specific Sirt6 knockout (aS6KO) mice, we explored whether adipocyte Sirt6 inhibits adipose tissue inflammation and its underlying mechanism. aS6KO mice fed normal chow gained more body weight and fat mass than wild-type mice and exhibited glucose intolerance and systemic insulin resistance. Measurement of plasma and tissue cytokines and flow cytometric analysis of adipose stromal vascular cells indicated a decrease in alternatively activated M2 macrophages in the adipose tissue of aS6KO mice. Mechanistically, Sirt6 regulated the expression of the canonical type 2 cytokine IL-4 by adipocytes in a cell autonomous manner, which in turn affects M2 macrophage polarization. Consistent with animal experimental data, the degree of obesity and insulin resistance demonstrated by the body mass index, fasting blood glucose and HbA1c correlated negatively with the expression of Sirt6 in human visceral fat tissues. Collectively, these results suggest that adipocyte Sirt6 regulates body weight gain and insulin sensitivity independent of diet, and the increased IL-4 production by Sirt6 and resultant M2 polarization of adipose tissue macrophages may attenuate proinflammatory responses in adipose tissue.