Non-invasive imaging biomarkers for liver steatosis in non-alcoholic fatty liver disease: present and future

Non-alcoholic fatty liver disease is currently the most common chronic liver disease, affecting up to 25% of the global population. Simple fatty liver, in which fat is deposited in the liver without fibrosis, has been regarded as a benign disease in the past, but it is now known to be prognostic. In the future, more emphasis should be placed on the quantification of liver fat. Traditionally, fatty liver has been assessed by histological evaluation, which requires an invasive examination; however, technological innovations have made it possible to evaluate fatty liver by non-invasive imaging methods, such as ultrasonography, computed tomography, and magnetic resonance imaging. In addition, quantitative as well as qualitative measurements for the detection of fatty liver have become available. In this review, we summarize the currently used qualitative evaluations of fatty liver and discuss quantitative evaluations that are expected to further develop in the future.

Natural History of Chronic Intestinal Pseudo-obstruction and Need for Palliative Care

Background/Aims@#Natural history of chronic intestinal pseudo-obstruction (CIPO), a rare disease characterized by episodes of non-mechanical obstruction, is unclear in adults. This study evaluates the clinical course of CIPO and palliative care needs of patients. @*Methods@#From October 2010 to September 2021, 74 patients who underwent cine MRI and had a definitive diagnosis of CIPO were prospectively included. We investigated disease etiology and outcomes, age at onset, nutritional status at consultation (body mass index and serum albumin), hydrogen breath test results, and total parenteral nutrition (TPN) during the disease course. @*Results@#Forty-seven patients (64%) were women, with a mean age of 44 years at onset and 49 years at diagnosis. Primary CIPO was observed in 48 patients (65%). Secondary CIPO was observed in 26 cases (35%), of whom 18 (69%) had scleroderma. The mean body mass index, serum albumin level, and hydrogen breath test positivity rate were 17 kg/m2 , 3.8 mg/dL, and 60%, respectively. TPN and invasive decompression therapy were required by 23 (31%) and 18 (24%) patients, respectively. Intestinal sterilization was performed in 51 (69%) patients and was effective in 33 (65%); of these, 28 (85%) were taking metronidazole. Seven (9%) patients used opioids. There were 9 deaths (12%), including 5 (56%) from infection and 2 (22%) from suicide. Of the deaths, 6 (67%) and 4 (44%) underwent TPN management and decompression therapy, respectively. Fifty-one patients (69%) wanted palliative care. @*Conclusion@#CIPO is a rare, severe, and under-recognized disease. Standardization of treatment strategies, including palliative care and psychiatric interventions, is desired.

Nonalcoholic Fatty Liver Disease as a Systemic Disease and the Need for Multidisciplinary Care

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease, and there has been a rapid increase in cases worldwide. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma and is also associated with an increased risk of cardiovascular disease or exacerbation of other organ diseases, thus posing a significant health problem from both a medical and a socioeconomic perspective. NAFLD is a systemic disease and requires the involvement of numerous medical professionals. Multidisciplinary collaboration, in which different professionals within different specialties come together and work together toward a common goal, supports better patient care by integrating perspectives of multiple experts and facilitating the exchange of opinions. Due to the large number of potential patients, gastroenterologists and hepatologists cannot manage the patients alone, and collaboration between specialists in various fields, including family doctors, dentists, nutritionists, and pharmacists is required for treatment of NAFLD. This review will discuss NAFLD from the perspective of various specialties and introduce multidisciplinary collaboration.

Endoscopic Ultrasound-Guided Gastroenterostomy for Afferent Loop Syndrome

Afferent loop syndrome (ALS) is a mechanical obstruction of the afferent limbs after gastrectomy with gastrojejunostomy reconstruction. Patients with cancer recurrence require immediate and less invasive treatment because of their poor condition. Percutaneous transhepatic/transluminal drainage (PTD) and endoscopic enteral stenting offer reasonable palliative treatment for malignant ALS but are not fully satisfactory in terms of patient quality of life (QoL) and stent patency. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using a lumen-apposing metal stent may address these shortcomings. Clinical data from 11 reports showed that all patients who had undergone EUS-GE had positive technical and clinical outcomes. The adverse event rate was 11.4%, including only mild or moderate abdominal pain, with no severe adverse events. Indirect comparative studies indicated that patients who had undergone EUS-GE had a significantly superior QoL, a higher clinical success rate, and a lower reintervention rate than those who had undergone PTD or endoscopic enteral stenting. Although the evidence is limited, EUS-GE may be considered as a first-line treatment for malignant ALS because it has better clinical outcomes than other less invasive treatments, such as PTD or endoscopic enteral stenting. Further prospective randomized control trials are necessary to establish EUS-GE as a standard treatment for ALS.

Endoscopic Self-Expandable Metal Stent Placement for Malignant Afferent Loop Obstruction After Pancreaticoduodenectomy: A Case Series and Review

In this study, we assessed a series of our cases in which endoscopic self-expandable metal stents (SEMSs) were used to treat malignant afferent loop obstruction (ALO) that arose after pancreaticoduodenectomy (PD). We retrospectively examined the records of 7 patients who underwent endoscopic SEMS placement for malignant ALO following PD. Clinical success was achieved in all cases. The median procedure time was 30 min (range, 15–50 min). There were no cases of stent occlusion, and no procedure-related adverse events were encountered. All patients died of their primary disease, and the median overall survival period was 155 days (range, 96–374 days). A re-intervention involving endoscopic ultrasound-guided hepaticogastrostomy combined with antegrade stenting was performed for obstructive jaundice and acute cholangitis in 1 case. In conclusion, endoscopic SEMS placement may be an effective and safe treatment for malignant ALO that arises after PD.

Selective Inhibition of β-Catenin/Co-Activator Cyclic AMP Response Element-Binding Protein-Dependent Signaling Prevents the Emergence of Hapten-Induced Atopic Dermatitis-Like Dermatitis

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.

Outcomes of Pneumonia Treatment in the Elderly by Pulmonologists or Non-Pulmonologists / 日本農村医学会雑誌

Pneumonia is common among elderly patients and the incidence among older adults is increasing in aging societies. If pulmonologists were to treat all cases of pneumonia, their work volume would be immense and the risk of burnout would increase. We reviewed cases of consecutive patients 70 years of age or older who were treated for pneumonia between November 2017 and October 2018 at Akita Kousei Medical Center. Of a total of 372 patients recruited for this study (214 men, mean age 85.6 years), 288 patients recovered and 84 (29.2%) died. The duration of admission differed significantly between the cardiovascular department and surgery department (p=0.03), between the renal unit of the internal medicine department and the neurosurgery department (p=0.01), and the renal unit of the internal medicine department and the surgery department (p=0.0005). Outcome was not significantly different among departments. It is crucial that pulmonologists and non-pulmonologists collaborate to treat pneumonia in old adults.

Small Bowel Obstruction After Ileal Pouch-Anal Anastomosis With a Loop Ileostomy in Patients With Ulcerative Colitis

PURPOSE: Small bowel obstruction (SBO) remains a common complication after pelvic or abdominal surgery. However, the risk factors for SBO in ulcerative colitis (UC) surgery are not well known. The aim of the present study was to clarify the risk factors associated with SBO after ileal pouch-anal anastomosis (IPAA) with a loop ileostomy for patients with UC. METHODS: The medical records of 96 patients who underwent IPAA for UC between 1999 and 2011 were reviewed. SBO was confirmed based on the presence of clinical symptoms and radiographic findings. The patients were divided into 2 groups: the SBO group and the non-SBO group. We also analyzed the relationship between SBO and computed tomography (CT) scan image parameters. RESULTS: The study included 49 male and 47 female patients. The median age was 35.5 years (range, 14–72 years). We performed a 2- or 3-stage procedure as a total proctocolectomy and IPAA for patients with UC. SBO in the pretakedown of the loop ileostomy after IPAA occurred in 22 patients (22.9%). Moreover, surgical intervention for SBO was required for 11 patients. In brief, closure of the loop ileostomy was performed earlier than expected. A multivariate logistic regression analysis revealed that the 2-stage procedure (odds ratio, 2.850; 95% confidence interval, 1.009–8.044; P = 0.048) was a significant independent risk factor associated with SBO. CT scan image parameters were not significant risk factors of SBO. CONCLUSION: The present study suggests that a 2-stage procedure is a significant risk factor associated with SBO after IPAA in patients with UC.

Age-Related Prevalence of Periodontoid Calcification and Its Associations with Acute Cervical Pain

STUDY DESIGN: Prospective study. PURPOSE: To assess the prevalence of periodontoid calcification and its associations with acute cervical pain. OVERVIEW OF LITERATURE: Calcium pyrophosphate dihydrate (CPPD) deposition disease is a common rheumatological disorder that occurs especially in elderly patients. Although CPPD crystals induce acute arthritis, these crystals are not usually symptomatic. Calcification surrounding the odontoid process (periodontoid calcification) has been reported to induce inflammation, resulting in acute neck pain. This disease is called crowned dens syndrome. Whether calcification induces inflammation or whether the crystals are symptomatic remains unclear. METHODS: The prevalence of periodontoid calcification at the atlas transverse ligament was examined by computed tomography of the upper cervical spine in patients suspected of brain disease but no cervical pain (control group, n=296), patients with pseudogout of the peripheral joints but no cervical pain (arthritis group, n=41), and patients with acute neck pain (neck pain group, n=22). Next, the correlation between the prevalence of periodontoid calcification and symptoms was analyzed. RESULTS: In the control group, 40 patients (13.5%) showed periodontoid calcification with no significant difference in the prevalence with gender. The prevalence of calcification increased significantly with age (p=0.002). In the arthritis group, 26 patients (63.4%) reported periodontoid calcification. In the neck pain group, 14 patients (63.6%) reported periodontoid calcification. Multiple logistic regression analysis by age and group revealed that higher age, inclusion in the arthritis group, and inclusion in the neck pain group significantly affected the prevalence of calcification. CONCLUSIONS: Our results cumulatively suggest that periodontoid calcification is an aging-related reaction and that calcification per se does not always cause neck pain. Periodontoid calcification was observed more frequently in patients with pseudogout of the peripheral joints and in those with acute neck pain than in asymptomatic control patients.

Perioperative Medical Complications after Posterior Approach Spinal Instrumentation Surgery for Osteoporotic Vertebral Collapse: A Comparative Study in Patients with Primary Osteoporosis and Those with Secondary Osteoporosis

STUDY DESIGN: A retrospective comparative study. PURPOSE: To compare perioperative medical complications after posterior approach spinal instrumentation surgery for osteoporotic vertebral collapse (OVC) between patients with primary osteoporosis and those with secondary osteoporosis. OVERVIEW OF LITERATURE: With increased aging of society, the demand for instrumentation surgery for an osteoporotic spine has been increasing. However, no studies have compared the rates or severities of perioperative complications after spinal instrumentation surgery between patients with primary osteoporosis and those with secondary osteoporosis. METHODS: Ninety-one patients with OVC aged ≥50 years (23 males and 68 females) who underwent posterior approach vertebral replacement with cages or posterior spinal fusion combined with vertebroplasty were divided into primary (n=56) and secondary (n=35) osteoporosis groups. Bone mineral density (BMD), osteoporosis treatment prior to OVC, operative invasiveness, and perioperative medical complications were compared. RESULTS: Diabetes mellitus (51.4%) was the most common cause of secondary osteoporosis, followed by glucocorticoid use (22.9%). No significant differences were seen in terms of age, gender, BMD, osteoporosis treatment, or operative invasiveness, including the number of levels fused, estimated blood loss, and number of patients requiring transfusion. No significant difference in the incidence of perioperative complications were observed between the primary and secondary osteoporosis groups (16.1% vs. 22.9%). However, surgical site infection (SSI) was significantly more frequently seen in the secondary osteoporosis group (11.4%) than in the primary osteoporosis group (1.8%; p<0.05). One patient in the secondary osteoporosis group developed methicillin-resistant Staphylococcus aureus infection that ultimately required instrument removal. CONCLUSIONS: The overall incidence of perioperative medical complications after posterior approach spinal instrumentation surgery for OVC was comparable between the primary and secondary osteoporosis groups under conditions of similar background characteristics and operative invasiveness. However, SSI (particularly more severe cases) occurred more frequently in patients with secondary osteoporosis.

Susceptibility of Aedes flavopictus miyarai and Aedes galloisi mosquito species in Japan to dengue type 2 virus

Objective: To evaluate the potential of local mosquitoes to act as vectors for dengue transmission in Japan. Methods: Serotype 2 ThNH28/93 was used to test the dengue susceptibility profiles of Aedes flavopictus miyarai (Ae. f. miyarai), Aedes galloisi (Ae. galloisi) and Aedes albopictus (Ae. albopictus), which were collected in Japan. We used Aedes aegypti from Thailand as a positive control. The mosquitoes were infected with the virus intrathoracically or orally. At 10 or 14 days post infection, the mosquitoes were dissected and total RNA was extracted from their abdomens, thoraxes, heads and legs. Mosquito susceptibility to dengue virus was evaluated using RT-PCR with dengue virus-specific primers. Differences in the infection and mortality rates of the different mosquito species were tested using Fisher's exact probability test. Results: The infection rates for dengue virus administered intrathoracically to Ae. f. miyarai, Ae. galloisi and Aedes aegypti mosquitoes were identical by RT-PCR on Day 10 post infection. All of the body parts we tested were RT-PCR-positive for dengue virus. For the orally administered virus, the infection rates in the different body parts of the Ae. f. miyarai mosquitoes were slightly higher than those of Ae. albopictus mosquitoes, but were similar to the control mosquitoes (P > 0.05). The mortality rates for Ae. f. miyarai and Ae. albopictus mosquitoes were similar (P = 0.19). Our data indicated that dengue virus was able to replicate and disseminate to secondary infection sites in all of the four mosquito species (Japanese and Thai). Conclusions: Ae. albopictus is a well-known candidate for dengue transmission in Japan. However, our data suggest that Ae. f. miyarai from Ishigaki Island (near Okinawa Island) and Ae. galloisi from Hokkaido (Northern Japan) should also be regarded as potential vectors for dengue transmission in these regions. Further studies on these mosquitoes should be conducted.

Comparison between Bilateral C2 Pedicle Screwing and Unilateral C2 Pedicle Screwing, Combined with Contralateral C2 Laminar Screwing, for Atlantoaxial Posterior Fixation

STUDY DESIGN: A retrospective study. PURPOSE: To compare clinical and radiological outcomes between bilateral C2 pedicle screwing (C2PS) and unilateral C2PS, combined with contralateral C2 laminar screwing (LS), for posterior atlantoaxial fixation. OVERVIEW OF LITERATURE: Posterior fixation with C1 lateral mass screwing (C1LMS) and C2PS (C1LMS-C2PS method) is an accepted procedure for rigid atlantoaxial stabilization. However, conventional bilateral C2PS is not always allowed in this method due to anatomical variations of C2 pedicles and/or asymmetry of the vertebral artery. Although unilateral C2PS plus contralateral LS (C2PS+LS) is an alternative in such cases, the efficacy of this procedure has not been evaluated in controlled studies (i.e., with bilateral C2PS as a control). METHODS: Clinical and radiological records of patients who underwent the C1LMS-C2PS method, using unilateral C2PS+LS (n=9), and those treated using conventional bilateral C2PS (n=10) were compared, with a minimum two years follow-up. RESULTS: Postoperative complications related to the unilateral C2PS+LS technique included one case of spontaneous spinous process fracture of C2. A C1 anterior arch fracture occurred after a fall in one patient, who underwent bilateral C2PS and C1 laminectomy. No significant differences were seen between the groups in reduction of neck pain after surgery or improvement of neurological status, as evaluated using the Japanese Orthopaedic Association score. A delayed union occurred in one patient each of the groups, with the final fusion rate being 100% in both groups. CONCLUSIONS: Clinical and radiological outcomes of unilateral C2PS+LS were comparable with those of the bilateral C2PS fixation technique for the C1LMS-C2PS method.

Anterior Decompression and Shortening Reconstruction with a Titanium Mesh Cage through a Posterior Approach Alone for the Treatment of Lumbar Burst Fractures

STUDY DESIGN: A retrospective study. PURPOSE: To examine the efficacy and safety for a posterior-approach circumferential decompression and shortening reconstruction with a titanium mesh cage for lumbar burst fractures. OVERVIEW OF LITERATURE: Surgical decompression and reconstruction for severely unstable lumbar burst fractures requires an anterior or combined anteroposterior approach. Furthermore, anterior instrumentation for the lower lumbar is restricted through the presence of major vessels. METHODS: Three patients with an L1 burst fracture, one with an L3 and three with an L4 (5 men, 2 women; mean age, 65.0 years) who underwent circumferential decompression and shortening reconstruction with a titanium mesh cage through a posterior approach alone and a 4-year follow-up were evaluated regarding the clinical and radiological course. RESULTS: Mean operative time was 277 minutes. Mean blood loss was 471 ml. In 6 patients, the Frankel score improved more than one grade after surgery, and the remaining patient was at Frankel E both before and after surgery. Mean preoperative visual analogue scale was 7.0, improving to 0.7 postoperatively. Local kyphosis improved from 15.7degrees before surgery to -11.0degrees after surgery. In 3 cases regarding the mid to lower lumbar patients, local kyphosis increased more than 10degrees by 3 months following surgery, due to subsidence of the cages. One patient developed severe tilting and subsidence of the cage, requiring additional surgery. CONCLUSIONS: The results concerning this small series suggest the feasibility, efficacy, and safety of this treatment for unstable lumbar burst fractures. This technique from a posterior approach alone offers several advantages over traditional anterior or combined anteroposterior approaches.