Reduced Tim-3 expression on human T-lymphotropic virus type I (HTLV-I) Tax-specific cytotoxic T lymphocytes in HTLV-I infection

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) and programmed cell death-1 (PD-1) are T cell exhaustion molecules. We investigated the expression of Tim-3 and PD-1 in human T-lymphotropic virus type I (HTLV-I) infection. Tim-3 expression, but not PD-1 expression, was reduced on CD4(+) and CD8(+) T cells of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and HTLV-I carriers as compared with healthy controls. Tim-3 expression was also reduced in HTLV-I Tax-specific cytotoxic T lymphocytes (CTLs) as compared with cytomegalovirus-specific CTLs. Tim-3(+), but not PD-1(+), Tax-specific CTLs produced less interferon-γ and exhibited low cytolytic activity. However, we observed no difference in the expression of Tim-3 or cytolytic activity between Tax-specific CTLs of HAM/TSP patients or carriers. Moreover, HTLV-I-infected CD4(+) T cells showed decreased Tim-3 expression. These data suggest that Tim-3 expression is reduced in HTLV-I infection and that a high number of Tim-3(-) HTLV-I-specific CTLs preserves their cytolytic activity, thereby controlling viral replication.     

Associations of symptomatic or asymptomatic peripheral arterial disease with all-cause mortality and cardiovascular mortality

BackgroundTo investigate the rate of all cause and cardiovascular mortality in patients with symptomatic or asymptomatic peripheral arterial disease (PAD) compared to those without PAD.Methods and resultsAll the subjects were inpatients at high risk of atherosclerosis and enrolled from February to November, 2006. A total of 320 were followed up until an end-point (death) was reached or until February 2010. The mean follow-up time was 37.7 ± 1.5 months. Compared with non-PAD, PAD patients had significantly higher rates of hypertension, diabetes mellitus, and smoking (P < 0.01). Those with symptomatic and asymptomatic PAD had a much higher all cause (37.5% and 23.0% vs. 12.1%) and cardiovascular mortality (18.8% and 13.8% vs. 6.7%) compared to those without PAD (P < 0.001). The symptomatic PAD patients were 1.831 times (95% CI: 1.222–2.741) as likely to die as those without PAD, and 1.646 times (95% CI: 1.301–2.083) in asymptomatic PAD patients after adjusting for other factors. Those with symptomatic or asymptomatic PAD were more than twice as likely to die of CVD as those without PAD (RR: 2.248, 95% CI: 1.366–3.698 and RR: 2.105, 95% CI: 1.566–2.831, respectively).ConclusionsPAD was associated with a higher all cause and cardiovascular mortality whether or not PAD is symptomatic.     

Squamous cell carcinoma arising in Verneuil's disease

BACKGROUND: Verneuil's disease or hidradenitis suppurativa is a chronic suppurative, and cicatricial inflammatory disease, mainly affecting apocrine-bearing area of the skin. Squamous cell carcinoma is an uncommon but a frightening complication of hidradenitis suppurativa. AIM: To report a new case of squamous cell carcinoma arising in Verneuil's disease. CASE REPORT: We reported a case of 60 year old man with a 30 years history of hidradenitis suppurativa in which squamous cell carcinoma arise. A wide surgical excision removing the tumour and leaving a large defect was performed. The patient had a well recovery, wounds healed well by primary intention. No recurrence observed at 18 months of follow up. CONCLUSION: Squamous cell carcinoma is an uncommon complication of hidradenitis suppurativa. Surgical excision represents also the treatment of choice.     

Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: role of B7-H1 as an anti-apoptotic molecule

Introduction

B7-H1 (PD-L1, CD274) is a T cell inhibitory molecule expressed in many types of cancer, leading to immune escape of tumor cells. Indeed, in previous reports we have shown an association of B7-H1 expression with high-risk breast cancer patients.

Methods

In the current study, we used immunohistochemistry, immunofluorescence and Western blot techniques to investigate the effect of neoadjuvant chemotherapy on the expression of B7-H1 in breast cancer cells.

Results

Among tested chemotherapeutic agents, doxorubicin was the most effective in downregulating cell surface expression of B7-H1 in vitro. These results were validated in vivo in a xenograft mouse model, as well as in murine heart tissue known to constitutively express B7-H1. The doxorubicin-dependent cell surface downregulation of B7-H1 was accompanied by an upregulation of B7-H1 in the nucleus. This re-distribution of B7-H1 was concurrent with a similar translocation of phosphorylated AKT to the nucleus. Inhibition of the PI3K/AKT pathway abrogated the doxorubicin-mediated nuclear up-regulation of B7-H1, suggesting an involvement of PI3K/AKT pathway in the nuclear up-regulation of B7-H1. Interestingly, siRNA knock down of B7-H1 lead to an increase in spontaneous apoptosis, as well as doxorubicin-induced apoptosis, which indicates an anti-apoptotic role for B7-H1 in breast cancer cells. The novel discovery of B7-H1 expression in the nuclei of breast cancer cells suggests that B7-H1 has functions other than inhibition of T cells.

Conclusions

Our findings explain the previously reported immunomodulatory effect of anthracyclines on cancer cells, and provide a link between immunoresistance and chemoresistance. Finally these results suggest the use of dual combinatorial agents to inhibit B7-H1 beside chemotherapy, in breast cancer patients.     

Endoscopic assessment and management of early esophageal adenocarcinoma

Esophageal carcinoma affects more than 450000 people worldwide and the incidence is rapidly increasing. In the United States and Europe, esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence. Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages. Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus. These risk factors include chronic gastroesophageal reflux disease, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity. The annual risk of esophageal cancer is approximately 0.25% for patients without dysplasia and 6% for patients with high-grade dysplasia. Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa. The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option. The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia. Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation, photodynamic therapy and cryoablation. Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion. Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor, positive lymph node and submucosal invasion. Surgical resection should be offered to patients with deep submucosal invasion.     

Day-of-surgery rejection of donors in living donor liver transplantation

AIM: To study diagnostic laparoscopy as a tool for excluding donors on the day of surgery in living donor liver transplantation (LDLT).METHODS: This study analyzed prospectively collected data from all potential donors for LDLT. All of the donors were subjected to a three-step donor evaluation protocol at our institution. Step one consisted of a clinical and social evaluation, including a liver profile, hepatitis markers, a renal profile, a complete blood count, and an abdominal ultrasound with Doppler. Step two involved tests to exclude liver diseases and to evaluate the donor’s serological status. This step also included a radiological evaluation of the biliary anatomy and liver vascular anatomy using magnetic resonance cholan-giopanc reatography and a computed tomography (CT) angiogram, respectively. A CT volumetric study was used to calculate the volume of the liver parenchyma. Step three included an ultrasound-guided liver biopsy. Between November 2002 and May 2009, sixty-nine potential living donors were assessed by open exploration prior to harvesting the planned part of the liver. Between the end of May 2009 and October 2010, 30 potential living donors were assessed laparoscopically to determine whether to proceed with the abdominal incision to harvest part of the liver for donation. RESULTS: Ninety-nine living donor liver transplants were attempted at our center between November 2002 and October 2010. Twelve of these procedures were aborted on the day of surgery (12.1%) due to donor findings, and eighty-seven were completed (87.9%). These 87 liver transplants were divided into the following groups: Group A, which included 65 transplants that were performed between November 2002 and May 2009, and Group B, which included 22 transplants that were performed between the end of May 2009 and October 2010. The demographic data for the two groups of donors were found to match; moreover, no significant difference was observed between the two groups of donors with respect to hospital stay, nar-cotic and non-narcotic analgesia requirements or the incidence of complications. Regarding the recipients, our study clearly revealed that there was no significant difference in either the incidence of different complications or the incidence of retransplantation between the two groups. Day-of-surgery donor assessment for LDLT procedures at our center has passed through two eras,open and laparoscopic. In the first era, sixty-nine LDLT procedures were attempted between November 2002 and May 2009. Upon open exploration of the donors on the day of surgery, sixty-five donors were found to have livers with a grossly normal appearance. Four donors out of 69 (5.7%) were rejected on the day of surgery because their livers were grossly fatty and pale. In the laparoscopic era, thirty LDLT procedures were attempted between the end of May 2009 and October 2010. After the laparoscopic assessment on the day of surgery, twenty-two transplantation procedures were completed (73.4%), and eight were aborted (26.6%). Our data showed that the levels of steatosis in the rejected donors were in the acceptable range. Moreover, the results of the liver biopsies of rejected donors were comparable between the group A and group B donors. The laparoscopic assessment of donors presents many advantages relative to the assessment of donors through open exploration; in particular, the laparo-scopic assessment causes less pain, requires a shorter hospital stay and leads to far superior cosmetic results. CONCLUSION: The laparoscopic assessment of donors in LDLT is a safe and acceptable procedure that avoids unnecessary large abdominal incisions and increases the chance of achieving donor safety.     

Impact of wearing personal protective equipment on the performance and decision making of surgeons during the COVID-19 pandemic: An observational cross-sectional study

During the coronavirus disease 2019 (COVID-19) pandemic, the mandatory use of personal protective equipment (PPE) has resulted in a significant reduction in the infection rate among health care workers (HCWs). However, there are some ongoing concerns about the negative impact of using PPE for prolonged periods.This study examined the impact of wearing PPE on surgeons’ performance and decision making during the COVID-19 pandemic.In this cross-sectional study, an anonymous online questionnaire was created and disseminated to surgeons all over the Eastern Province of Saudi Arabia. The questionnaire included the demographic data, the local hospital policies, the non-technical skills (e.g., communication, vision, and comfort) and the technical skills, and the process of decision making.From June 2020 to August 2020, 162 surgeons participated in this questionnaire. Of them, 80.2% were aged from 26 to 45 years, 70.4% have received a special training for PPE, and 59.3% of participants have operated on COVID-19 confirmed cases. A negative impact of wearing PPE was reported on their overall comfort, vision, and communication skills (92.6%, 95.1%, and 82.8%, respectively). The technical skills and decision making were not significantly affected (60.5% and 72.8%, respectively). More preference for conservative approach, damage control procedures, and/or open approach was reported.Despite its benefits, PPE is associated with a significant negative impact on the non-technical skills (including vision, communication, and comfort) as well as a non-significant negative impact on technical skills and decision making of surgeons. Extra efforts should be directed to improve PPE, especially during lengthy pandemics.