Insecticide resistance in potential vector mosquitoes for West Nile virus in Japan

Culex pipiens complex is the significant vector mosquito of West Nile virus. To take stock of the current situation of insecticide susceptibilities and design an ideal mosquito control strategy, we collected Culex pipiens pallens Coquillet, Culex pipiens form molestus Forskal, and Culex quinquefasciatus Say from fields in Japan and conducted bioassays for five larvicides (fenitrothion, temephos, etofenprox, diflubenzuron, and pyriproxyfen) by using a larval dipping method. Among five insecticides tested, obvious reduced susceptibilities were observed for etofenprox, which is the only pyrethroid compound registered as a larvicide in Japan. Twenty-two of 56 colonies exhibited a >10% survival rate at the etofenprox concentration of 5.7 microg/ml, which is a 10 times higher concentration of the working solution. The LC50 of a colony collected from Fukuoka prefecture for etofenprox exceeded 60 microg/ml (resistance ratio >2,307), and this colony also exhibited cross-resistance to other pyrethroids, permethrin (299-fold) and phenothrin (1,200-fold). The insect growth regulators diflubenzuron and pyriproxyfen were found to be sufficiently effective enough to control Culex larvae present, but decreased sensitivities to these insecticides were slightly detected in some colonies of Cx. p. form molestus collected from urban areas. Several etofenprox-resistant colonies of Cx. p. form molestus exhibited simultaneously decreased susceptibilities to other insecticides, including temephos, diflubenzuron, and pyriproxyfen.     

Comparison of surgical outcomes and split renal function between laparoscopic and robot-assisted partial nephrectomy: a propensity score-matched analysis

Purpose

The objective of this study was to compare perioperative outcomes and total and split renal function between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). Predictive risk factors of preservation of operated renal function were also assessed.

Methods

We retrospectively analyzed 173 patients who underwent LPN (n?=?84) or RAPN (n?=?89) between 2010 and 2020. After propensity score matching (1:1), perioperative outcomes and total and split renal function were assessed. Logistic regression analysis was used to evaluate predictive risk factors of preservation of operated renal function. Trifecta criteria were defined as negative surgical margins, warm ischemia time (WIT)?<?25 min, and no complications more than Clavien–Dindo grade II within 4 weeks after surgery. Split renal function was evaluated by mercaptoacetyltriglycine renal scan.

Results

After propensity score matching, 42 patients were allocated to each group. RAPN was associated with significantly shorter WIT (RAPN vs LPN: 12 vs 22 min; p?<?0.0001) and higher trifecta achievement rate (93.3 vs 64.2%; p?<?0.0001). Other perioperative outcomes and total and split renal function were not significantly different between LPN and RAPN. The R.E.N.A.L. nephrometry score (RNS) was a predictive risk factor of preservation of operated renal function in the multivariable logistic regression analysis (odds ratio 1.68, 95% confidence interval 1.29–2.20, p?<?0.0001).

Conclusions

RAPN improved WIT and trifecta achievement rate, but it did not improve the preservation of operated renal function, for which RNS was found to be a strong predictive risk factor.

     

Preoperative change of modified Glasgow prognostic score after stenting predicts the long-term outcomes of obstructive colorectal cancer

Inflammation-based markers predict the long-term outcomes of various malignancies. We investigated the relationship between the modified Glasgow prognostic score (mGPS) and the long-term outcomes of obstructive colorectal cancer in patients who underwent self-expandable metallic colonic stent placement and subsequently received curative surgery. We retrospectively analyzed 63 consecutive patients with pathological stage II and III obstructive colorectal cancer from 2013 to 2018. The mGPS was calculated before stenting and surgery, and the difference of the scores was defined as the d-mGPS. All d-mGPS = 2 patients were > 70 years of age (p = 0.01). Postoperative complications were more common in the preoperative mGPS = 2 group (p = 0.02). The postoperative hospital stay was significantly longer in the mGPS = 2 group (p = 0.007). Multivariate analyses revealed that d-mGPS was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] = 9.18, p = 0.004) and cancer-specific survival (HR = 9.98, p = 0.01). Preoperative mGPS = 2 was significantly associated with poor OS (HR = 5.53, p = 0.04). The results indicated that mGPS might serve as a valuable indicator of the immunonutritional status of preoperative patients, and a preoperative change of the status might affect the long-term outcomes of patients with obstructive colorectal cancer.     

A new prognostic score for the survival of patients with esophageal squamous cell carcinoma

Purpose

Recent studies have shown that the modified Glasgow Prognostic Score (mGPS), which is an inflammation-based prognostic score, is useful as a prognostic index for some cancer cases. The purpose of this study was to create a prognostic scoring system for patients with esophageal squamous cell carcinoma (ESCC) that was more independent and sensitive than the mGPS.

Methods

One hundred sixty-eight patients who had undergone esophagectomy for ESCC were included in the study. The new mGPS (NmGPS) was calculated based on the following cutoff values: CRP >0.75 mg/dL indicated NmGPS 1 or 2, depending on the absence or presence of hypoalbuminemia (<3.5 g/dL); and CRP ≤0.75 mg/dL indicated NmGPS 0. We also performed an analysis based on cutoff values of 0.5 and 0.25 mg/dL for CRP.

Results

Only the NmGPS with a cutoff CRP value of 0.5 mg/dL was able to divide into three independent patient groups in the survival curves. In the multivariate analyses, a NmGPS (CRP cutoff; 0.5 mg/dL) of 2 was a more significant independent prognostic factor (HR 4.437, 95 % CI 2.000–9.844, p = 0.0002) than a mGPS of 2 (HR 2.726, 95 % CI 1.021–7.112, p = 0.0449).

Conclusions

The new prognostic score NmGPS (CRP cutoff; 0.5 mg/dL) was more independent and sensitive than the mGPS for patients with ESCC.     

Stem cell factor‐activated bone marrow ameliorates amyotrophic lateral sclerosis by promoting protective microglial migration

Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with motor neuron death. Several experimental treatments, including cell therapy using hematopoietic or neuronal stem cells, have been tested in ALS animal models, but therapeutic benefits have been modest. Here we used a new therapeutic strategy, bone marrow transplantation (BMT) with stem cell factor (SCF)‐ or FMS‐like tyrosine kinase 3 (flt3)‐activated bone marrow (BM) cells for the treatment of hSOD1(G93A) transgenic mice. Motor function and survival showed greater improvement in the SCF group than in the group receiving BM cells that had not been activated (BMT alone group), although no improvement was shown in the flt3 group. In addition, larger numbers of BM‐derived cells that expressed the microglia marker Iba1 migrated to the spinal cords of recipient mice compared with the BMT‐alone group. Moreover, after SCF activation, but not flt3 activation or no activation, the migrating microglia expressed glutamate transporter‐1 (GLT‐1). In spinal cords in the SCF group, inflammatory cytokines tumor necrosis factor‐α and interleukin‐1β were suppressed and the neuroprotective molecule insulin‐like growth factor‐1 increased relative to nontreatment hSOD1(G93A) transgenic mice. Therefore, SCF activation changed the character of the migrating donor BM cells, which resulted in neuroprotective effects. These studies have identified SCF‐activated BM cells as a potential new therapeutic agent for the treatment of ALS. © 2014 Wiley Periodicals, Inc.     

An autopsy case of meningeal carcinomatosis with parenchymal invasion through the cranial and spinal nerve roots

Meningeal carcinomatosis is a well‐known complication of malignant neoplasms. We report a case of meningeal carcinomatosis of 2 months' duration in a 22‐year‐old man, in whom the initial symptom was gradually worsening headache. Postmortem examination revealed infiltrating adenocarcinoma of the stomach. Carcinoma cells showed diffuse spread to the subarachnoid space of the brain and spinal cord. In many places, subarachnoid tumor cells had infiltrated to the cranial and spinal nerves. Moreover, carcinoma cells in the nerve roots extended to the parenchyma of the brain and spinal cord beyond the CNS‐peripheral nervous system junction. These findings suggest that cranial and spinal nerve roots can be a possible route of parenchymal invasion in meningeal carcinomatosis.     

Nuclear Notch3 Expression is Associated with Tumor Recurrence in Patients with Stage II and III Colorectal Cancer

Background

The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.

Methods

The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.

Results

Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).

Conclusions

Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.     

Blood pressure after treatment with sodium–glucose cotransporter 2 inhibitors influences renal composite outcome: Analysis using propensity score-matched models

Aims/IntroductionSodium–glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease.Materials and MethodsWe assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post‐treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of <92 mmHg (n = 280) for propensity score matching (1:1 nearest neighbor match with 0.04 of caliper value and no replacement). The end‐point was a composite of progression of albuminuria or a decrease in the estimated glomerular filtration rate by ≥15% per year.ResultsBy propensity score matching, a matched cohort model was constructed, including 201 patients in each group. The incidence of renal composite outcome was significantly lower among patients with MAP of <92 mmHg than among patients with MAP of ≥92 mmHg (n = 11 [6%] vs n = 26 [13%], respectively, P = 0.001). The change in estimated glomerular filtration rate was similar in the two groups; however, the change in the albumin‐to‐creatinine ratio was significantly larger in patients with MAP of <92 mmHg.ConclusionsIn Japanese type 2 diabetes mellitus patients with chronic kidney disease, blood pressure after SGLT2i administration influences the renal composite outcome. Blood pressure management is important, even during treatment with SGLT2i.