A 59-year-old man clinically diagnosed with primary lung cancer underwent left lower lobectomy and lymph node dissection( ND2a-2). The postoperative pathological stage was ⅠB(pT2aN0M0), and the lesion was positive for epidermal growth factor receptor(EGFR)exon 21 L858R mutation. Thirty months after surgery, the patient developed pleural dissemination and effusion in the left pleural cavity. Carboplatin(AUC=6, day 1, every 3 weeks)and nab-paclitaxel(100 mg/m2, day 1 and day 8, every 3 weeks)were administered as first-line therapy. Progressive disease was evident 10 months after 4 courses of first-line therapy. Pembrolizumab(200 mg, day 1, every 3 weeks)was then administered as second-line therapy. After 7 months(9 courses of therapy), the lung cancer had metastasized to the left third intercostal muscle, and the pleural nodules regrew. The former lesion was treated with radiotherapy owing to the development of pain in the chest. Erlotinib (150 mg once daily)and bevacizumab(15 mg/kg, day 1, every 3 weeks)were initiated as third-line therapy, resulting in complete response at 14 months(67 months after surgery, 37 months after postoperative recurrence). The prognosis of patients with EGFR-positive pulmonary adenosquamous carcinoma and undergoing treatment with EGFR-tyrosine kinase inhibitors(TKI)is reportedly poor. Herein, we report a rare case of adenosquamous carcinoma with EGFR mutation presenting complete response following treatment with EGFR-TKI.A man in his 40s underwent a transbronchial lung biopsy and received a diagnosis of adenocarcinoma of the right upper lobe of the lung(cT4N0M0, Stage Ⅲ)with no EGFR gene mutation, no ALK fusion gene, no ROS1 fusion gene, and a tumor proportion score(TPS)of 50-74%. During the postoperative follow-up period, enlarged right supraclavicular lymph nodes and right upper and lower paratracheal lymph nodes were detected, diagnosed as recurrence by positron emission tomography-computed tomography. Although a positive rheumatoid factor test, as the patient had no symptoms of rheumatoid arthritis(RA), treatment with pembrolizumab was initiated. Before the second treatment course, a pharmacist conversing with the patient observed that the patient was experiencing pain in his fingers. After discussing the possibility of treatment continuation and test items with the attending physician, the patient underwent tests and received a diagnosis of RA.A 72-year-old woman underwent sigmoid colon resection plus D2 lymph node dissection in 2008, with additional resection after endoscopic mucosal resection(EMR). Histopathological examination revealed only atypical ducts in the EMR scar, with no invasion below the submucosa. No lymphatic, venous, or nerve invasions were confirmed, and oral and anal stumps and lymph node metastases were negative. She was followed up for 5 years after the surgery, and no recurrence was detected. In 2018, she visited our hospital with the chief complaint of diarrhea and constipation. Colonoscopy revealed a circumferential lesion around the anastomosis. She underwent laparoscopic low anterior resection for suspected anastomotic recurrence, which was confirmed by histopathological diagnosis. The anastomotic recurrence 10 years after surgery for SM cancer of the colon with negative lymph node metastasis and vascular factor was extremely rare. We recognized the importance of surveillance 5 years after surgery.A 62-year-old woman underwent upper endoscopy in January 2009 to reveal the presence of an extrinsic compression measuring approximately 3 cm in the anterior wall of the gastric antrum. Further examinations suggested that it was caused by peritoneal cancer of an unknown origin; thus, staging laparoscopy was performed in May 2009. Multiple white nodules of varying sizes were found scattered throughout the right upper quadrant of the abdomen and the right abdomen. Based on a biopsy of the greater omentum, the patient was diagnosed with papillary serous adenocarcinoma. As no abnormalities were observed in the uterus and ovary, it was suspected that the patient had primary peritoneal cancer. Hence, in July 2009, the patient underwent resection of the greater omentum, gastric pylorus, gall bladder, and right hemicolon where the tumors were localized, as well as bilateral adnexectomy. Based on intraoperative findings and postoperative histology, the patient was diagnosed with high-grade primary peritoneal serous adenocarcinoma and received paclitaxel and carboplatin therapy. Subsequent follow-up examinations, including positron emission tomography-computed tomography(PET-CT), indicated repeated recurrences in the mesentery, the pelvic floor, and around the remnant stomach. After identifying these recurrences, the patient was treated with platinum-based drugs, experiencing repeated response and cessation cycles. Since September 2019, the patient has received olaparib therapy. PET-CT examination performed in September 2020 indicated that the patient remained in complete remission.Chemotherapy is the standard treatment for unresectable gastric cancer, but there is no clear evidence of therapeutic lymphadenectomy in conversion surgery after the tumor shrinks or the combined effect of perioperative chemotherapy. A 63-year-old man was diagnosed with advanced gastric cancer by upper gastrointestinal endoscopy; computed tomography (CT)showed swelling of the gastric regional lymph nodes, abdominal para-aortic lymph nodes, and left supraclavicular lymph node. After 4 courses of combination therapy with S-1 and cisplatin(SP therapy), CT showed that the left supraclavicular lymph node disappeared and the para-aortic lymph node was reduced. Distal gastrectomy and D2 plus para-aortic lymph node dissection were performed as conversion surgery. Two courses of postoperative SP therapy were administered, and S-1 monotherapy was continued for 2 years and 6 months. After 5 years and 1 month since the operation, the patient is alive without recurrence. This case shows that SP therapy can be effective as chemotherapy for unresectable gastric cancer. In addition, that conversion surgery after chemotherapy may contribute to recurrence-free survival.In the present report, the patient was a 55-year-old woman who had undergone an oophorectomy in October 2016 as surgical intervention for ovarian cancer, followed by 6 courses of TC therapy as postoperative adjuvant therapy. She was diagnosed with recurrent ovarian cancer in August 2017, and we planned anticancer drug treatment considering that the tumor exhibited platinum resistance. However, the platelet count decreased significantly to 2.4×104/μL. Accordingly, she was referred to the hematology department and was diagnosed with idiopathic thrombocytopenic purpura. She was started on oral eltrombopag, and her platelet level recovered to 5.8×104/μL on day 68. Next, gemcitabine plus bevacizumab therapy was initiated. However, as the platelet level again decreased to 1.6×104/μL on day 8, the eltrombopag dose was increased only for 5 days before and after the anticancer drug administration on day 1. Accordingly, after increasing the eltrombopag dose, the anticancer drug treatment was performed without interruptions. Moreover, the gemcitabine dose could be increased. Herein, we report that in patients with platinum-resistant recurrent ovarian cancer complicated with idiopathic thrombocytopenic purpura, increasing the oral hematopoietic stimulant dose for 5 days before and after day 1 had beneficial results in continuing anticancer drug treatment.In elderly patients aged≥80 with newly diagnosed multiple myeloma(NDMM), the optimal initial doses of bortezomib (Bor)and lenalidomide(Len)remain unclear. We performed a retrospective analysis that included 20 patients with NDMM aged≥80 years who underwent treatment with Bor or Len at our hospital from July 2010 to December 2019. Among the patients treated with Bor, the median time to next treatment(TTNT)was 4.2 months, and the median dose was 1.0 mg/m2 per injection. While patients with International Staging System(ISS)Ⅲ or an estimated glomerular filtration rate of less then 40 mL/ min/1.73 m2 required dose reductions, dose intensity did not significantly affect TTNT. Among the patients treated with Len, the median TTNT was 14.6 months, and the median dose of Len was 10.0 mg/day. All patients who started with6le;10 mg Len continued the initial dose; the others required a dose reduction. Treatment was discontinued in 2 patients because of disease progression and in other 15 patients because of adverse events(AEs). In conclusion, initial doses of Bor at 1.0 mg/ m2 per injection and Len at 10 mg per day may provide potent disease control and permit continuing treatment with few AEs in elderly patients with MM.Neuropathic pain in patients with cancer often do not respond to both opioid and non-opioid analgesics. Tapentadol has two medical effects action on the μ opioid receptor and inhibition of noradrenaline reuptake; thus, it is expected to be effective for neuropathic pain. We investigated its effect on neuropathic pain in 40 patients with cancer who received tapentadol between June 2017 and May 2020 at the Japanese Red Cross Nagoya Daini Hospital. We compared the level of neuropathic pain using an NRS before and after tapentadol administration. The NRS score(median)decreased from 7 to 4.5 within 15 days after first administration or dose increase(p less then 0.05). Twenty-two patients(55%)showed more than 33% improvement in the NRS score. These results suggest that tapentadol may contribute to a reduction in neuropathic pain.Olaparib, an anticancer drug, requires daily administration, frequently causing nausea. Elucidation of the influential factors for nausea is important for continuing treatment. We retrospectively examined 23 patients who received olaparib treatment and were divided into nausea and no-nausea groups, according to antiemetic prescriptions during treatment. We compared the patients’ background and laboratory values between the 2 groups. Nine patients developed nausea and 14 did not, with mean body weights at treatment initiation of 49.9±9.8 kg and 60.0±13.9 kg, respectively. Body weights were significantly lower in the nausea than in the no-nausea group. Four weeks after olaparib administration, the logarithmic difference in the fluctuation of the neutrophil count was -0.145±0.154 and 0.095±0.242, while the fluctuation of the lymphocyte count was -0.169±0.053 and -0.060±0.110 in the nausea and no-nausea groups, respectively, with the former significantly lower than the latter. The treatment period for the nausea group was significantly longer than that for the no-nausea group. Since olaparib is administrated as a flat dose, the dose per body weight increased in underweight patients. Thus, being underweight might have impacted the efficacy of olaparib, including the development of side effects such as nausea and hematotoxicity.To assess the efficacy and safety of ramucirumab in combination with FOLFIRI in patients with unresectable metastatic colorectal cancer under clinical practice in Japan, we reviewed manuscripts reporting clinical research, including case reports, of Japanese patients with FOLFIRI plus ramucirumab therapy published starting from 2016, when ramucirumab was approved as a treatment for metastatic colorectal cancer in Japan, to June 2020. We also reviewed an interim report of post-marketing surveillance study. The efficacy of ramucirumab in combination with FOLFIRI including irinotecan 150 mg/m2, which is the recommended dose in Japan and is used as initial dose in Japanese clinical practice, was similar to that of the global, phase 3 RAISE study with irinotecan 180 mg/m2. The desirable effect of FOLFIRI plus ramucirumab was observed in patients with wild-type RAS, primary tumors on the left sides(descending, sigmoid, or rectum colons), or who received anti-epidermal growth factor receptor agents, including panitumumab or cetuximab, as previous treatment. Also, the effectiveness of FOLFIRI plus ramucirumab as a late-line treatment was suggested. Several patients were reported to have nephrosis syndrome after starting ramucirumab, but they recovered with discontinuation of ramucirumab and appropriate treatment. No new safety concerns were observed from the literature or the interim report of post-marketing surveillance study.Precision medicine, which considers the genetics of the tumor tissues and cells for selection of the most appropriate treatment strategy, has recently been developed for colorectal cancer. The BRAF mutation status in colorectal cancer has been tested, but precision medicine for BRAF-mutated tumors had not been applicable due to no approved BRAF-targeting drugs until recently. In addition, conventional standard chemotherapy for BRAF-mutated colorectal cancer show limited effectiveness, resulting in poor prognosis. Therefore, we need new drugs specific for BRAF-mutated colorectal cancer. In this review, we outline the characteristics, development, and new treatment strategies for BRAF-mutated colorectal cancer. In addition, we introduce the BEACON CRC study, which prospectively evaluated the efficacy and safety of combination therapy of encorafenib(BRAF inhibitor), binimetinib(MEK inhibitor), and cetuximab(anti-EGFR antibody)in patients with metastatic colorectal cancer with the BRAF V600E-mutation.Cancer patients often have oral complications during cancer therapies that can be followed by various systemic complications. If these oral complications remain untreated and worsen, cancer treatment has to be postponed or suspended. In recent years, the importance of oral supportive care for cancer patients has been recognized and that medical-dental collaboration is the key to solving these problems. Close cooperation between medical and dental professionals will prevent oral complications, and so treatment can continue without delay or hindrance. Also, the quality of life of the cancer patient can be improved. Many current anticancer drug treatments are performed as outpatient treatments. However, the number of dentists working in hospitals is small and it is difficult for them to manage all cancer patients. Therefore, oral supportive care in hospital dentistry is not sufficient and patients have to see a local dentist. It is highly recommended that the patient has a „family dentist”and undergo regular oral examinations and dental care. In Japan, the Japan Dental Association has established a regional dentist cooperation system to seamlessly provide appropriate oral supportive care to cancer patients. The policy is to provide patients with continuous oral supportive care not only before the start of treatment, but also during and after treatment. In addition, hospital professionals and family dentists work together to exchange information and provide support and dental care for oral problems, depending on the status of cancer treatment and the needs of the patient.Regarding regional cooperation in palliative care for advanced cancer, the problem is complicated by the fact that the 3 factors of hospital circumstances, regional circumstances, and the patient’s own wishes are different. Depending on the hospital, the patient can be seen to the end, the palliative care resources are different depending on the region, and the patient’s own wishes also change depending on the time. When considering the characteristic trajectory that a cancer patient will follow to the end, it is essential to prepare early, but what is important here is a double primary care physician system consisting of a cancer therapist and palliative care. However, in communication when introducing palliative care, it is important to consider the timing and the feeling that the patient has been abandoned. This period is an important point for patients, how to spend the end of their lives, and it is desirable to think carefully about how to approach it according to the region. Palliative care is not only medical care for dying, but also medical care that supports how to live at the end of life.We conducted a questionnaire survey of cancer patients and medical institutions to examine the usage status and problems of the regional cooperation critical pathway (cooperation path). In a survey of medical institutions, 65% of respondents said that using a cooperation path was beneficial, which was a significant increase from the previous survey in 2014. According to a survey on workload, about 30% of doctors felt that the workload increased in 2018 as well as in 2014. On the other hand, hospital profits increased at twice as many medical institutions compared to 2014. According to surveys of cancer patients, 80% of patients said that they were happy to use the cooperation path. However, a small percentage of patients disagreed with the use of the cooperation path. In this questionnaire survey, it was found that not only doctors but also patients understand the merits of the cooperation path.Based on the basic plan to promoting cancer control programs, a cooperation between designated cancer care hospitals and regional medical institutions was outlined. Regional designated cancer care hospitals supports the system of regional cancer medical treatment cooperation, and prefectural designated cancer care hospital manage a prefectural cancer medical treatment cooperation. Although system is progressing, such as sharing regional cooperation pass and holding multi-facility joint meetings to promote regional cooperation, there are regional disparities, and we believe that further promotion is necessary.Armed antibodies, of which are representative antibody-drug conjugate(ADC)and radioimmunotherapy(RIT), are attracting attention as next-generation antibody drugs with high efficacy and low side effects. Armed antibodies require clinically optimized adaptation and development strategies, in addition to the fusion of basic technologies such as organic chemistry, protein chemistry, imaging technology, structural biology, and biomarker research. In armed antibodies, the antibody is only a carrier for deliver and its therapeutic effect affects the specificity/strength of the payload, which is the effector agent for target molecules on cell surface. An ADC with a bystander effect is a promising drug for solid tumors with heterogeneous target molecule expression. Aside from the next-generation ADC DS8201, new ADCs are being developed at an accelerated pace, demonstrating new therapeutic possibilities. In the future, it will be necessary to optimize predictors of therapeutic effect based on the MOA of ADC.

During the last decades, surgeons of several specialties presenting different levels of expertise in colon handling have been involved in laparoscopic procedures. The aim of the present experimental study was to investigate the feasibility of TISSEELTM versus the conventional suture placement technique on confined bowel lesions in rats.

Twenty-four Sprague-Dawley rats underwent confined bowel perforation and were divided into three groups the SUTURE group (sutures were used), the SUTURE + TISSEELTM group (sutures and TISSEELTM were utilized), and the TISSEELTM group (only TISSEELTM was used). Blinded histopathologic analysis followed animal sacrifice.

The median weight of the rats was 526 ± 50 g. A single animal had hematochezia on the first postoperative day. Cessation of bleeding at the perforation margin was indicated intraoperatively after TISSEELTM application. Animals in the TISSEELTM group presented less intraperitoneal adhesions and lower hemorrhagic infiltration compared to animals of the two other groups. In addition, animals in the TISSEELTM group showed thrombus formation at the bowel perforation site compared to animals of the two other groups (p = 0.042). Histopathologic analysis demonstrated reduced inflammatory reaction (p = 0.003), diminished fibrosis (p = 0.001), and better tissue regeneration (p = 0.000) in the TISSEELTM group compared to the other two groups.

Application of TISSEELTM at the perforation site was associated with increased regeneration of the intestinal wall and less inflammatory and fibrotic reaction compared to suture placement. However, more experimental and clinical studies should be conducted before implementation in humans.

Application of TISSEELTM at the perforation site was associated with increased regeneration of the intestinal wall and less inflammatory and fibrotic reaction compared to suture placement. However, more experimental and clinical studies should be conducted before implementation in humans.

An alarming increase in vitamin D deficiency even in sunny regions highlights the need for a better understanding of the genetic background of the vitamin D endocrine system and the molecular mechanisms of gene polymorphisms of the vitamin D receptor (VDR). In this study, the serum levels of 25(OH)D3 were correlated with common VDR polymorphisms (ApaI, BsmI, FokI, and TaqI) in 98 subjects of a Greek homogeneous rural population.

25(OH)D3 concentration was measured by ultra-HPLC, and the VDR gene polymorphisms were identified by quantitative real-time PCR followed by amplicon high-resolution melting analysis.

Subjects carrying either the B BsmI (OR 0.52, 95% CI 0.27-0.99) or t TaqI (OR 2.06, 95% 1.06-3.99) allele presented twice the risk for developing vitamin D deficiency compared to the reference allele. Moreover, subjects carrying 1, 2, or all 3 of these genotypes (BB/Bb, Tt/tt, and FF) demonstrated 2-fold (OR 2.04, 95% CI 0.42-9.92), 3.6-fold (OR 3.62, 95% CI 1.07-12.2), and 7-fold (OR 6.92, 95% CI 1.68-28.5) increased risk for low 25(OH)D3 levels, respectively.

Our findings reveal a cumulative effect of specific VDR gene polymorphisms that may regulate vitamin D concentrations explaining, in part, the paradox of vitamin D deficiency in sunny regions, with important implications for precision medicine.

Our findings reveal a cumulative effect of specific VDR gene polymorphisms that may regulate vitamin D concentrations explaining, in part, the paradox of vitamin D deficiency in sunny regions, with important implications for precision medicine.

Femoral arterial dysfunction including abnormal vascular responsiveness to endogenous ligands was often seen in arterial hypertension. Extracellular nucleotides including uridine 5′-diphosphate (UDP) and uridine 5′-triphosphate (UTP) play important roles for homeostasis in the vascular system including controlling the vascular tone. However, responsiveness to UDP and UTP in femoral arteries under arterial hypertension remains unclear. The aim of this study was to investigate if hypertension has an effect of vasoconstrictive responsiveness to UDP and UTP in femoral arteries of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) after 7 and 12 months old.

Organ baths were conducted to determine vascular reactivity in isolated femoral arterial rings.

In femoral arteries obtained from 12-month-old rats, augmented contractile responses to UDP and UTP were seen in femoral arteries of SHR than in those of WKY under situations not only intact but also nitric oxide synthase inhibition, whereas no difference of extracellular potassium-induced vasocontraction was seen in both SHR and WKY groups. Similar contraction trends occurred in femoral arteries obtained from 7-month-old rats. Moreover, contractions induced by UDP and UTP were increased in endothelium-denuded arteries. Cyclooxygenase inhibition decreased the contractions induced by these nucleotides and abolished the differences in responses between the SHR and WKY groups.

This study demonstrates the importance of regulation of extracellular uridine nucleotides-induced contractions in hypertension-associated peripheral arterial diseases.

This study demonstrates the importance of regulation of extracellular uridine nucleotides-induced contractions in hypertension-associated peripheral arterial diseases.

Recent studies have shown that inflammatory processes might play a role in epileptogenesis. Their role in ictogenesis is much less clear. The aim of this study was to investigate peri-ictal changes of the innate immune system by analyzing changes of immune cells, as well as pro- and anti-inflammatory cytokines.

Patients with active epilepsy admitted for video-EEG monitoring for presurgical evaluation were included. Blood was sampled every 20 min for 5 h on 3 consecutive days until a seizure occurred. After a seizure, additional samples were drawn immediately, as well as 1 and 24 h later. To analyze the different populations of peripheral blood mononuclear cells, all samples underwent FACS for CD3, CD4, CD8, CD56, CD14, CD16, and CD19. For cytokine analysis, we used a custom bead-based multiplex immunoassay for IFN-γ, IL-1β, IL-1RA, IL-4, IL-6, IL-10, IL-12, IL-17, MCP-1, MIP-1α, and TNFα.

Fourteen patients with focal seizures during the sampling period were included. Natural killer (NK) cells showed a negative correlation (ρ = -0.3362, p = 0.0195) before seizure onset and an immediate increase to 1.95-fold afterward. T helper (TH) and B cells decreased by 2 and 8%, respectively, in the immediate postictal interval. Nonclassical and intermediate monocytes decreased not until 1 day after the seizures, and cytotoxic T (TC) cells showed a long-lasting postictal increase by 4%. IL-10 and MCP-1 increased significantly after seizures, and IL-12 decreased in the postictal phase.

Our study argues for a role of the innate immune system in the pre- and postictal phases. NK cells might be involved in preictal changes or be altered as an epiphenomenon in the immediate preictal interval.

Our study argues for a role of the innate immune system in the pre- and postictal phases. NK cells might be involved in preictal changes or be altered as an epiphenomenon in the immediate preictal interval.

The pathogenesis and pulmonary histopathological characteristics of hypersensitivity pneumonitis (HP) are not yet fully understood. Therefore, we established animal models of HP of different stages, aiming to provide support for research on this disease.

We established rat models of pigeon breeder’s lung of different pathological types by creating freeze-dried allergen powder from fresh pigeon feathers, dander, and other droppings. Freeze-dried allergen powder suspensions of pigeon droppings were used to establish 2 rat models of HP, one by aerosol inhalation and one by airway instillation, and the rats were sacrificed after different lengths of time to observe the pathological changes in their lung tissues.

By the 40th week after allergen inhalation, granulomas were the main changes in the model, without fibrotic changes. When using airway instillation to establish the model, at the 20th week, group 1 (low dose + twice/week) and group 2 (medium dose + twice/week) showed granuloma changes, but no fibrosis; group 3 (high dose + once/week) and group 4 (high dose + twice/week) both showed obvious pulmonary fibrotic changes, but the death rate of rats in group 4 was greater.

Both aerosol inhalation and airway instillation of freeze-dried pigeon allergen powder can successfully establish an HP model. The airway instillation method can cause pulmonary fibrotic changes in a short time, and the pulmonary pathological changes of animal models manifest with an obvious time-dose effect.

Both aerosol inhalation and airway instillation of freeze-dried pigeon allergen powder can successfully establish an HP model. The airway instillation method can cause pulmonary fibrotic changes in a short time, and the pulmonary pathological changes of animal models manifest with an obvious time-dose effect.

Colorectal cancer (CRC), the third most common cancer globally, caused 881,000 cancer deaths in 2018. Toll-like receptors (TLRs), the primary sensors of pathogen-associated molecular patterns and damage-associated molecular patterns, activate innate and adaptive immune systems and participate in the development of an inflammatory tumor microenvironment. We aimed to explore the prognostic value of TLR3, TLR5, TLR7, and TLR9 tissue expressions in CRC patients.

Using immunohistochemistry, we analyzed tissue microarray samples from 825 CRC patients who underwent surgery between 1982 and 2002 at the Department of Surgery, Helsinki University Hospital, Finland. After analyzing a pilot series of 205 tissue samples, we included only TLR5 and TLR7 in the remainder of the patient series. We evaluated the associations between TLR5 and TLR7 tissue expressions, clinicopathologic variables, and survival. Using the Kaplan-Meier method, we generated survival curves, determining significance using the log-rank test. Univariate and multivariate survival analyses relied on the Cox proportional hazards model.

The 5-year disease-specific survival was 55.9% among TLR5-negative (95% confidence interval [CI] 50.6-61.2%) and 61.9% (95% CI 56.6-67.2%; p = 0.011, log-rank test) among TLR5-positive patients. In the Cox multivariate survival analysis adjusted for age, sex, stage, location, and grade, positive TLR5 immunoexpression (hazard ratio [HR] 0.74; 95% CI 0.59-0.92; p = 0.007) served as an independent positive prognostic factor. TLR7 immunoexpression exhibited no prognostic value in the survival analysis across the entire cohort (HR 0.97; 95% CI 0.78-1.20; p = 0.754) nor in subgroup analyses.

We show for the first time that a high TLR5 tumor tissue expression associates with a better prognosis in CRC patients.

We show for the first time that a high TLR5 tumor tissue expression associates with a better prognosis in CRC patients.

Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD).

We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 μmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the diand bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.

Bullous pemphigoid (BP) is a common autoimmune blistering skin disease with substantial mortality.

To identify whether the use of immunosuppressants was associated with reduced mortality in BP patients.

The data for this study were obtained from the National Health Insurance Research Database in Taiwan from January 1, 1997 to December 31, 2013. Those BP patients receiving any immunosuppressant for ≥28 days per month for 3 consecutive months were defined as the immunosuppressant cohort. In total, 452 BP patients on immunosuppressants were matched 14 by age, sex, propensity score of comorbidities, and use of tetracycline with 1,808 BP patients taking only corticosteroids.

The immunosuppressant cohort had a significantly lower 5-year mortality rate than the corticosteroid cohort (0.57 vs. 0.67). In the multivariable regression analysis adjusted for covariates, the use of immunosuppressants significantly reduced the risk of mortality (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.68-0.90, p < 0.001). Hyperlipidemia also reduced risk of mortality. However, age, diabetes, renal disease, chronic obstructive pulmonary disease, cerebrovascular disease, and dementia were significant risk factors for mortality. In the subgroup analysis, the risk of mortality decreased most substantially in those aged <70 years (HR 0.45, 95% CI 0.28-0.72).

Immunosuppressant use was associated with a 22% reduced risk of BP mortality. The effects were more substantial in those aged <70 years, with a 55% reduced risk of mortality.

Immunosuppressant use was associated with a 22% reduced risk of BP mortality. The effects were more substantial in those aged less then 70 years, with a 55% reduced risk of mortality.

The pathogenesis of preeclampsia (PE) is associated with impaired trophoblast invasion, which results in placental insufficiency. Our earlier studies demonstrated that tissue transglutaminase (tTG) is highly expressed in human PE serum. However, whether tTG participates in trophoblast invasion remains unclear. The aim of the present study was to determine the role and mechanism of tTG in regulating matrix metalloproteinase (MMP)-2/MMP-9 expression to reduce trophoblast invasiveness in PE.

HTR-8/SVneo cells were transfected with a lentivirus vector and small interfering RNA targeting tTG. The protein level was detected by Western blotting. Cell proliferation and apoptosis were assessed by MTS and flow cytometry assays, respectively. Cell invasion was investigated by Transwell assay. In addition, the influence of tTG on PI3K and AKT mRNA levels in HTR-8/SVneo cells was evaluated using reverse transcription-quantitative PCR.

tTG-overexpression inhibited HTR-8/SVneo cell proliferation and invasion and promoto modulation of tTG expression as a potential therapeutic target for PE.Nocardia spp. are filamentous Actinobacteria of the order Corynebacteriales and mostly known for their ability to cause localized and systemic infections in humans. However, the onset and progression of nocardiosis is only poorly understood, in particular the mechanisms of strain-specific presentations. Recent genome sequencing has revealed an extraordinary capacity for the production of specialized small molecules. Such secondary metabolites are often crucial for the producing microbe to survive the challenges of different environmental conditions. An interesting question thus concerns the role of these natural products in Nocardia-associated pathogenicity and immune evasion in a human host. In this review, a summary and discussion of Nocardia metabolites is presented, which may play a part in nocardiosis because of their cytotoxic, immunosuppressive and metal-chelating properties or otherwise vitally important functions. This review also contains so far unpublished data concerning the biosynthesis of these molecules that were obtained by detailed bioinformatic analyses.Neurodevelopmental disorders (NDDs) that affect cognition, social interaction, and learning, including autism spectrum disorder (ASD) and intellectual disability (ID), have a strong genetic component. Our current understanding of risk genes highlights two main groups of dysfunction those in genes that act as chromatin modifiers and those in genes that encode for proteins localized at or near synapses. Understanding how dysfunction in these genes contributes to phenotypes observed in ASD and ID remains a major question in neuroscience. In this review, we highlight emerging evidence suggesting that dysfunction in dendrites – regions of neurons that receive synaptic input – may be key to understanding features of neuronal processing affected in these disorders. Dendritic integration plays a fundamental role in sensory processing, cognition, and conscious perception, processes hypothesized to be impaired in NDDs. Many high-confidence ASD genes function within dendrites where they control synaptic integration and dendritic excitability. Further, increasing evidence demonstrates that several ASD/ID genes, including chromatin modifiers and transcription factors, regulate the expression or scaffolding of dendritic ion channels, receptors, and synaptic proteins. Therefore, we discuss how dysfunction of subsets of NDD-associated genes in dendrites leads to defects in dendritic integration and excitability and may be one core phenotype in ASD and ID.

Both polypharmacy and frailty are highly prevalent among the patients on hemodialysis and associated with adverse outcomes; however, little is known about the association between them.

We examined 337 patients enrolled in the ACTIVE/ADIPOSE dialysis cohort study between 2009 and 2011. The number of prescribed medications and frailty were assessed at baseline, 12, and 24 months. Frailty was defined based upon the Fried’s frailty phenotype. We used logistic regression with generalized estimating equations to model the association of the number of medications and frailty at baseline and over time. A competing-risk regression analysis was also used to assess the association between the number of medications and incidence of frailty.

The mean number of medications was 10 ± 5, and 94 patients (28%) were frail at baseline. Patients taking >11 medications showed higher odds for frailty than the patients taking fewer than 8 medications (OR 1.54, 95% CI 1.05-2.26). During the 2-year of follow-up, 87 patients developed frailty among those who were nonfrail at baseline. Compared with the patients taking fewer than 8 medications, the incidence of frailty was approximately 2-fold in those taking >11 medications (sub-distribution hazard ratio 2.15, 95% CI 1.32-3.48).

Using a higher number of medications was associated with frailty and the incidence of frailty among hemodialysis patients. Minimizing polypharmacy may reduce the incidence and prevalence of frailty among dialysis patients.

Using a higher number of medications was associated with frailty and the incidence of frailty among hemodialysis patients. Minimizing polypharmacy may reduce the incidence and prevalence of frailty among dialysis patients.

The objective of this study was to demonstrate the association between changes in different obesity indicators and the risk of incident hypertension by the age-group among community-dwelling residents in southern China.

A total of 6,959 non-hypertensive participants aged ≥18 years old were enrolled in this cohort study and completed questionnaire interviews and anthropometric measurements at baseline (2010) and follow-up (2017). A time-dependent covariate Cox proportional hazard model considered the changes in obesity indicators during the follow-up period and calculated the hazard ratios (HRs) to analyze the risk of incident hypertension according to different obesity indicators.

During a mean follow-up of 7.1 years, 1,904 participants were newly diagnosed with hypertension. The body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were significantly positively associated with an increased future risk of incident hypertension, and BMI was the best predictive indicator of hypertension (obesity in men HR = 2.65, 95% confidence interval (CI) = 2.20-3.20; obesity in women HR = 2.80, 95% CI = 2.27-3.45). Compared with the middle-aged and older group, the risk of incident hypertension was highest in the younger group which had the highest baseline obesity indicators.

Changes in obesity indicators were significantly associated with the risk of incident hypertension in all age-groups, and the risk of future incident hypertension increased with the increase in baseline obesity indicators.

Changes in obesity indicators were significantly associated with the risk of incident hypertension in all age-groups, and the risk of future incident hypertension increased with the increase in baseline obesity indicators.

Chronic spontaneous urticaria (CSU) is a common cutaneous disease caused by mast-cell degranulation. Human β-defensin 2 (HBD2) is a well-known antimicrobial peptide that is also a pruritogen inducing vascular permeability via non-IgE-mediated mast-cell degranulation.

We investigated the associations between serum HBD2 levels and the clinical characteristics of CSU patients.

Serum samples from 124 CSU patients and 56 healthy controls were screened for the levels of HBD2 and translationally controlled tumor protein (TCTP)_ by using ELISA. The urticaria activity score over 7 days (UAS7) was used to measure disease activity in CSU patients. Accompanying angioedema was self-reported.

Serum HBD2 levels were higher in the CSU group than in healthy subjects (median [interquartile range], 84.1 [43.5, 142.5] vs. 59.5 [26.7, 121.5], p = 0.034). In CSU patients, serum HBD2 level was negatively correlated with the peripheral basophil percentages (Spearman’s rho = -0.229, p = 0.01) and vitamin D levels (-0.262, p = 0.02), but positively correlated with TCTP levels (0.252, p = 0.006). In CSU patients, HBD2 level was higher in those with than without angioedema (101.7 [50.9, 184.2] vs. 66.7 [37.9, 132.0], p = 0.019). It did not differ by aspirin hypersensitivity or atopy status, or autologous serum skin test positivity.

A known mast-cell degranulator, HBD2 was elevated in the sera from CSU patients compared to healthy controls and may be involved in the pathogenesis of accompanying angioedema.

A known mast-cell degranulator, HBD2 was elevated in the sera from CSU patients compared to healthy controls and may be involved in the pathogenesis of accompanying angioedema.

We conducted a scoping review of dietary guidelines with the intent of developing a position paper by the „IUNS Task force on Dietary Fat Quality” tasked to summarize the available evidence and provide the basis for dietary recommendations.

We systematically searched several databases and Web sites for relevant documents published between 2015 and 2019.

Twenty documents were included. Quantitative range intake recommendations for daily total fat intake included boundaries from 20 to 35% of total energy intake (TEI), for monounsaturated fat (MUFA) 10-25%, for polyunsaturated fat (PUFA) 6-11%, for saturated-fat (SFA) ≤11-≤7%, for industrial trans-fat (TFA) ≤2-0%, and <300-<200 mg/d for dietary cholesterol. The methodological approaches to grade the strength of recommendations were heterogeneous, and varied highly between the included guidelines. Only the World Health Organization applied the GRADE approach and graded the following recommendation as „strong” to reduce SFA to below 10%, and TFA to below 1% and replace both with PUFA if SFA intake is greater than 10% of TEI.

Although the methodological approaches of the dietary guidelines were heterogeneous, most of them recommend total fat intakes of 30-≤35% of TEI, replacement of SFA with PUFA and MUFA, and avoidance of industrial TFA.

Although the methodological approaches of the dietary guidelines were heterogeneous, most of them recommend total fat intakes of 30-≤35% of TEI, replacement of SFA with PUFA and MUFA, and avoidance of industrial TFA.

Foot-and-mouth disease (FMD) is an infectious and highly contagious disease of cloven-hoofed domestic and wild animals, causing heavy economic losses to the livestock industry. Rapid and reliable diagnosis of the disease is essential for the implementation of effective control measures. This study compared sandwich enzyme-linked immunosorbent assay (S-ELISA) and conventional reverse transcription polymerase chain reaction (RT-PCR) for the diagnosis of FMD.

A total of 60 epithelial samples from suspected cases of FMD were tested using both S-ELISA and RT-PCR assays. The level of agreement between the assays was assessed by calculating the Kappa value.

S-ELISA detected 38 (63%) samples positive for FMD virus (FMDV). Being predominant, serotype O was detected in 22 (57.9%) of the total samples tested positive, whereas 9 (23.7%) and 7 (18.4%) samples were found positive for serotypes A and Asia-1, respectively. RT-PCR detected viral genome in 51 (85%) of the samples using pan-FMDV primers set, 1F/1R. Thirtyensitive, and definitive diagnosis of FMD in resource-constrained countries. Samples giving negative results in S-ELISA should be tested in RT-PCR for the disease detection and virus typing.

The degree to which a family history of coronary heart disease (FHCHD) is associated with silent cerebral small-vessel disease (cSVD) among healthy adults, independent of prevalent CHD and traditional risk factors, is unknown.

The Atherosclerosis Risk in Communities (ARIC) study is a community-based cohort study with self-reported family history data and brain magnetic resonance imaging (ages 68-88). The association between markers of cSVD (lacunar infarcts and cerebral microbleeds), or log-transformed white matter hyperintensity (WMH) volume, and FHCHD, or the number of affected relatives was examined using separate adjusted logistic or linear regression models, respectively. Race interaction terms were evaluated.

Of 1,639 participants without prevalent CHD (76 ± 5 years, 62% female, 29% black), 686 (42%) had FHCHD. There were higher odds of lacunar infarct (OR 1.40, 95% CI 1.07-1.84) among those with parental FHCHD and higher odds of microhemorrhages (lobar OR 1.86, 95% CI 1.13-3.06; subcortical OR 1.47, 95% CI 1.01-2.15) among those with sibling FHCHD. A greater number of any relative affected was associated with higher odds of lacunar infarct (OR 1.24, 95% CI 1.04-1.47) and lobar microhemorrhages (OR 1.31, 95% CI 1.05-1.64) but not subcortical microhemorrhages (OR 1.09, 95% CI 0.92-1.28). Odds of having a lacunar infarct were higher among blacks (p-interaction 0.04) with paternal FHCHD (OR 2.20, CI 1.35-3.58) than whites with paternal FHCHD (OR 1.17, CI 0.87-1.56). There was no association with WMH.

Markers of cSVD, specifically lacunar infarcts and microhemorrhages, appear to be associated with FHCHD, potentially representing shared mechanisms in different vascular beds, and perhaps a genetic propensity for vascular disease.

Markers of cSVD, specifically lacunar infarcts and microhemorrhages, appear to be associated with FHCHD, potentially representing shared mechanisms in different vascular beds, and perhaps a genetic propensity for vascular disease.

The aim of this study was to identify the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a predictor of overall prognosis in patients with hepatocellular carcinoma treated with lenvatinib.

Forty-eight consecutive patients who received lenvatinib treatment were reviewed. The oncological aggressiveness of tumors estimated using 18F-FDG-PET/CT was investigated by the analysis of progression-free survival (PFS), post-progression survival (PPS), and overall survival (OS). Multivariate analysis was used to identify potential confounders for OS during lenvatinib therapy.

Using the Modified Response Evaluation Criteria in Solid Tumors, a tumor-to-normal liver ratio (TLR) ≥2, indicating higher oncological aggressiveness in HCCs, was associated with a better objective response to lenvatinib than a TLR <2 (78 vs. 62%), resulting in a similar PFS (p = 0.751). Because of a significantly worse PPS, OS with a TLR ≥2 was poor compared to a TLR < 2 (p = 0.012). Multivariate analysis confirmed that a TLR ≥ 2 was associated with poor OS (hazard ratio, 2.709; 95% CI, 1.140-6.436; p = 0.024). Analysis of 24 patients who received a repeat 18F-FDG-PET/CT showed that daily changes expressed as ΔTLR × 103/day over the treatment course tended to be different among the types of subsequent treatment. A R0 resection and lenvatinib-TACE sequential therapy provided good disease control (median, -4.593 and -0.024, respectively) compared with other treatments (median, 5.278) (p = 0.075).

Lenvatinib has acceptable disease control regardless of estimated tumor differentiation. A high TLR (≥2) is a poor prognostic factor of OS following lenvatinib treatment, while ΔTLR × 103/day provides useful information of disease control status.

Lenvatinib has acceptable disease control regardless of estimated tumor differentiation. A high TLR (≥2) is a poor prognostic factor of OS following lenvatinib treatment, while ΔTLR × 103/day provides useful information of disease control status.

The prevalence of malnutrition among inpatient older adults is as high as 20∼50%. Masticatory performance is known to affect the nutritional status of individuals. However, an objective measurement to reflect the real status of masticatory muscle performance is lacking at the bedside.

This pilot study analyzed the masticatory performance using surface electromyography (sEMG) of masticatory muscles that measures both muscle strength and muscle tone at the bedside. The nutritional status was measured using the Mini Nutritional Assessment tool. The handgrip strength was measured using a hand dynamometer. The statistical data were analyzed using SPSS 25 software.

The data revealed that female inpatient older adults more frequently had substandard handgrip strength (p = 0.028), an at-risk and poor nutritional status (p = 0.005), and a higher masseter muscle tone (p = 0.024). Inpatient older adults with an at-risk and poor nutritional status had an older age (p = 0.016), lower handgrip strength (p = 0.001), and higher average masseter muscle tone (p = 0.01). A high masseter muscle tone predicted the risk of having an at-risk and poor nutritional status. The at-risk or poor nutritional status predicted having a substandard handgrip strength by 5-fold.

A high masticatory muscle tone predicts malnutrition and frailty. Medical professionals should combat masticatory dysfunction-induced malnutrition by detecting masticatory muscle performance using sEMG and referring patients to dental professionals. Additionally, encouraging inpatient older adults to perform oral motor exercise is recommended.

A high masticatory muscle tone predicts malnutrition and frailty. Medical professionals should combat masticatory dysfunction-induced malnutrition by detecting masticatory muscle performance using sEMG and referring patients to dental professionals. Additionally, encouraging inpatient older adults to perform oral motor exercise is recommended.

Transcutaneous bilirubin (TcB) measurement offers a noninvasive approach for bilirubin screening; however, its accuracy in preterm infants is unclear. This study determined the agreement between TcB and total serum bilirubin (TSB) among preterm infants.

A multisite prospective cohort study was conducted at 3 NICUs in Ontario, Canada, September 2016 to June 2018. Among 296 preterm infants born at 240/7 to 356/7 weeks, 856 TcB levels were taken at the forehead, sternum, and before and after the initiation of phototherapy with TSB measurements. Bland-Altman plots and 95% limits of agreement (LOA) expressed agreement between TcB and TSB.

The overall mean TcB-TSB difference was -24.5 μmol/L (95% LOA -103.3 to 54.3), 1.6 μmol/L (95% LOA -73.4 to 76.5) before phototherapy, and -31.1 μmol/L (95% LOA -105.5 to 43.4) after the initiation of phototherapy. The overall mean TcB-TSB difference was -15.2 μmol/L (95% LOA -86.8 to 56.3) at the forehead and -24.4 μmol/L (95% LOA -112.9 to 64.0) at the sternum. The mean TcB-TSB difference was -31.