Toll‐like receptor 4 differentially regulates adult hippocampal neurogenesis in an age‐ and sex‐dependent manner

Toll‐like receptor 4 (TLR4) is primarily responsible for initiating an immune response following pathogen recognition. However, TLR4 is also expressed on neural progenitor cells and has been reported to regulate hippocampal neurogenesis as young male TLR4 knockout mice show increases in cell proliferation and doublecortin positive cells. Whether these effects occur in both sexes and are sustained with normal aging is currently unknown. The present study evaluated whether TLR4 deficiency alters adult hippocampal neurogenesis in young (3–4 months) and aged (18–20 months), male and female, TLR4 deficient (TLR4?/?; B6.B10ScN‐Tlr4lps‐del/JthJ) and wild type (WT) mice. Additionally, neurogenesis within the dorsal and the ventral hippocampal subdivisions was evaluated to determine if TLR4 has differential effects across the hippocampus. Bromodeoxyuridine (BrdU) was administered to quantify new cell survival as well as cell differentiation. Ki‐67 was measured to evaluate cell proliferation. Results show that young TLR4?/? females had higher rates of proliferation and neuronal differentiation in both the dorsal and ventral hippocampus relative to WT females. Young TLR4?/? males show elevated proliferation and neuronal differentiation mainly in the ventral hippocampus. While young TLR4?/? mice show enhanced neurogenesis compared to young WT mice, the increase was not apparent in the aged TLR4?/? mice. Both aged WT and TLR4?/? mice showed a decrease in proliferation, new cell survival, and neuronal differentiation compared to young WT and TLR4?/? mice. The data collectively indicate that TLR4 regulates hippocampal neurogenesis in young adults, but that these effects are region‐specific in males and that females show broader changes in neurogenesis throughout the hippocampus.     

Lymph node pick up by separate stations: Option or necessity

AIM: To evaluate whether lymph node pick up by separate stations could be an indicator of patients submitted to appropriate surgical treatment. METHODS: One thousand two hundred and three consecutive gastric cancer patients submitted to radical resection in 7 general hospitals and for whom no information was available on the extension of lymphatic dissection were included in this retrospective study. RESULTS: Patients were divided into 2 groups: group A, where the stomach specimen was directly formalinfixed and sent to the pathologist, and group B, where lymph nodes were picked up after surgery and fixed for separate stations. Sixty-two point three percent of group A patients showed 16 retrieved lymph nodes compared to 19.4% of group B(P 0.0001). Group B(separate stations) patients had significantly higher survival rates than those in group A [46.1 mo(95%CI: 36.5-56.0) vs 27.7 mo(95%CI: 21.3-31.9); P = 0.0001], independently of T or N stage. In multivariate analysis, group A also showed a higher risk of death than group B(HR = 1.24; 95%CI: 1.05-1.46).CONCLUSION: Separate lymphatic station dissection increases the number of retrieved nodes, leads to better tumor staging, and permits verification of the surgical dissection. The number of dissected stations could potentially be used as an index to evaluate the quality of treatment received.     

Pressure support ventilation vs spontaneous ventilation via ProSeal™ laryngeal mask airway in pediatric patients undergoing ambulatory surgery: a randomized controlled trial

Aim: To investigate the advantages of using pressure support ventilation (PSV) vs spontaneous ventilation via ProSeal? laryngeal mask airway in children undergoing ambulatory surgery. Background: In our ambulatory surgical unit, the use of unassisted spontaneous breathing via laryngeal mask airway is a common anesthetic technique during general anesthesia. However, this may be associated with inadequate ventilation. PSV is a ventilatory mode that is synchronized with the patient’s respiratory effort and may improve gaseous exchange under general anesthesia. Materials and methods: After the approval from the ethics committee, a randomized controlled trial involving 24 pediatric patients was conducted in our ambulatory surgical unit. They were randomized into two groups, namely Group PSV (receiving PSV) and Group SV (unassisted spontaneous ventilation). Outcome measures included intraoperative respiratory and hemodynamic parameters as well as recovery room data. Results: There were no significant differences in baseline characteristics between the two groups. Patients in Group PSV had lower ETCO₂ (42.8 ± 5.8 vs 50.4 ± 4.0, P = 0.001) and higher expiratory tidal volume per kg bodyweight (8.3 ± 1.8 ml kg^?1 vs 5.8 ± 0.8 ml kg^?1, P = 0.001) compared with patients in Group SV. There were no significant differences in other respiratory and hemodynamic parameters or recovery room data between the two groups. Conclusion: Pressure support ventilation via ProSeal? laryngeal mask airway during general anesthesia improves ventilation in pediatric patients undergoing ambulatory surgery. However, this did not translate to a difference in clinical outcome among our study patients.     

Revision of loop colostomy under regional anaesthesia and sedation

Patients presenting for emergency abdominal procedures often have medical issues that cause both general anaesthesia and central neuraxial blockade to pose significant risks. Regional anaesthetic techniques are often used adjunctively for abdominal procedures under general anaesthesia, but there is limited published data on procedures done under peripheral nerve or plexus blocks. We herein report the case of a patient with recent pulmonary embolism and supraventricular tachycardia who required colostomy refashioning. Ultrasonography-guided regional anaesthesia was administered using a combination of ilioinguinal-iliohypogastric, rectus sheath and transversus abdominis plane blocks. This was supplemented with propofol and dexmedetomidine sedation as well as intermittent fentanyl and ketamine boluses to cover for visceral stimulation. We discuss the anatomical rationale for the choice of blocks and compare the anaesthetic conduct with similar cases that were previously reported.     

Epithelial cell identity in hyperplastic precursors of breast cancer

Introduction:In the adult human breast, hyperplastic enlarged lobular unit (HELU) and atypical ductal hyperplasia (ADH) are two common abnormalities that frequently coexist with ductal carcinoma in sit...     

Primary care-based intervention to reduce at-risk drinking in older adults: a randomized controlled trial

Aims To examine whether a multi‐faceted intervention among older at‐risk drinking primary care patients reduced at‐risk drinking and alcohol consumption at 3 and 12 months. Design Randomized controlled trial. Setting Three primary care sites in southern California. Participants Six hundred and thirty‐one adults aged ≥ 55 years who were at‐risk drinkers identified by the Comorbidity Alcohol Risk Evaluation Tool (CARET) were assigned randomly between October 2004 and April 2007 during an office visit to receive a booklet on healthy behaviors or an intervention including a personalized report, booklet on alcohol and aging, drinking diary, advice from the primary care provider and telephone counseling from a health educator at 2, 4 and 8 weeks. Measurements The primary outcome was the proportion of participants meeting at‐risk criteria, and secondary outcomes were number of drinks in past 7 days, heavy drinking (four or more drinks in a day) in the past 7 days and risk score. Findings At 3 months, relative to controls, fewer intervention group participants were at‐risk drinkers [odds ratio (OR) 0.41; 95% confidence interval (CI) 0.22–0.75]; they reported drinking fewer drinks in the past 7 days [rate ratio (RR) 0.79; 95% CI 0.70–0.90], less heavy drinking (OR 0.46; 95% CI 0.22–0.99) and had lower risk scores (RR 0.77 95% CI 0.63–0.94). At 12 months, only the difference in number of drinks remained statistically significant (RR 0.87; 95% CI 0.76–0.99). Conclusions A multi‐faceted intervention among older at‐risk drinkers in primary care does not reduce the proportions of at‐risk or heavy drinkers, but does reduce amount of drinking at 12 months.     

Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan,Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial

We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250?mg (days ?21 and ?14), Y-90 ibritumomab IV (.4?m Ci/kg, day ?14), fludarabine 30?mg/m² i.v. (days ?3 and ?2) plus melphalan 70?mg/m² i.v. (days ?3 and ?2) or 1 dose of melphalan and thiotepa 5?mg/kg (day ?8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P?=?.046) and OS (71% versus 27%, P?=?.047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.