Targeting Both Autophagy and Immunotherapy in Breast Cancer Treatment.

As clinical efforts towards breast-conserving therapy and prolonging survival of those with metastatic breast cancer increase, innovative approaches with the use of biologics are on the rise. Two areas of current focus are cancer immunotherapy and autophagy, both of which have been well-studied independently but have recently been shown to have intertwining roles in cancer. An increased understanding of their interactions could provide new insights that result in novel diagnostic, prognostic, and therapeutic strategies. In this breast cancer-focused review, we explore the interactions between autophagy and two clinically relevant immune checkpoint pathways; the programmed cell death-1 receptor with its ligand (PD-L1)/PD-1 and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)/CD80 and CD86 (B7-1 and B7-2). Furthermore, we discuss emerging preclinical and clinical data supporting targeting both immunotherapy and autophagy pathway manipulation as a promising approach in the treatment of breast cancer.

Anatomical Variations of the Sinonasal Area and Their Clinical Impact on Sinus Pathology: A Systematic Review

Abstract Introduction Anatomical variations of the nasal cavity and of the paranasal sinuses are frequently encountered and play an important role in dysfunctional drainage of sinuses. However, it is not clear in the literature whether they predispose to sinus pathology. Objectives The aim of the present review is to summarize the understanding of the association between anatomical variations of the sinonasal area and sinus pathology. Data Synthesis The present review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We performedathorough research on PubMed from October2004 until May 2020 byusing the search terms paranasal sinus anatomical variations and sinus disease, sinusitis, and mucosal disease. Thirty studies were eligible and were included in the analysis. Overall, the studies encompassed a total of 6,999 patients included in the present review. In many studies, it has been statistically established that certain anatomical variations increase the risk of sinus disease. On the other hand, the rest of the collected studies failed to show any statistically significant correlation between anatomical variants and sinus pathology. Conclusion The present study highlights the possible correlation between some anatomical variations of the sinonasal area and pathologies of the paranasal sinuses. Careful assessment and computed tomography (CT) in patients with chronic rhinosinusitis is needed, especially in those undergoing endoscopic surgery, to identify and treat anatomical variations in the paranasal sinuses that may be correlated with rhinosinusitis. Due to contradictory results in the literature, further research is needed to elucidate the effects of anatomical variants of the sinonasal area.

Anatomical Variations of the Sinonasal Area and Their Clinical Impact on Sinus Pathology: A Systematic Review.

Introduction Anatomical variations of the nasal cavity and of the paranasal sinuses are frequently encountered and play an important role in dysfunctional drainage of sinuses. However, it is not clear in the literature whether they predispose to sinus pathology. Objectives The aim of the present review is to summarize the understanding of the association between anatomical variations of the sinonasal area and sinus pathology. Data Synthesis The present review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We performed a thorough research on PubMed from October 2004 until May 2020 by using the search terms paranasal sinus anatomical variations and sinus disease , sinusitis , and mucosal disease . Thirty studies were eligible and were included in the analysis. Overall, the studies encompassed a total of 6,999 patients included in the present review. In many studies, it has been statistically established that certain anatomical variations increase the risk of sinus disease. On the other hand, the rest of the collected studies failed to show any statistically significant correlation between anatomical variants and sinus pathology. Conclusion The present study highlights the possible correlation between some anatomical variations of the sinonasal area and pathologies of the paranasal sinuses. Careful assessment and computed tomography (CT) in patients with chronic rhinosinusitis is needed, especially in those undergoing endoscopic surgery, to identify and treat anatomical variations in the paranasal sinuses that may be correlated with rhinosinusitis. Due to contradictory results in the literature, further research is needed to elucidate the effects of anatomical variants of the sinonasal area.

The Impact of Vascular Loops in the Cerebellopontine Angle on Audio-Vestibular Symptoms: A Systematic Review.

It has been suggested that vascular loops in the cerebellopontine angle and internal auditory canal are involved in the etiology of audio-vestibular symptoms. Several studies have focused on the compression of the eighth cranial nerve by vascular loops but have yielded contradictory results regarding their clinical significance. The aim of this study was to investigate whether vascular loops in this region correlate with audio-vestibular symptoms and which loop features - if any - can potentially lead to symptom manifestation. This systematic review was conducted according to the PRISMA guidelines. We performed on PubMed a literature search from November 2005 to October 2020. The search strategy included the following keywords ("vascular loops" OR "AICA loops" OR "vascular compression syndrome") AND ("hearing loss" OR "tinnitus" OR "vertigo"). Fifteen studies were eligible and included in the analysis. Overall, the studies encompassed a total of 11,788 patients included in this review. The significantly larger group of patients (70%), in which no correlation of symptoms with vascular loops was found, suggests that vascular loops are probably anatomic variations in a substantial majority of cases with an uncommon subset causing some audio-vestibular symptoms. Even within the papers claiming a correlation, there is a multitude of symptoms that did not correlate with vascular loops. It has been suggested by most authors that magnetic resonance imaging should be performed to exclude the role of a vascular loop in the etiology of audio-vestibular symptoms only when vascular compression syndrome is suspected based on clinical indications and not routinely. Further studies would be useful in order to detail the relationship between the vascular structures and the nervous system.

Alterations of the 70 kDa heat shock protein (HSP70) and sequestosome-1 (p62) in women with breast cancer.

Peripheral blood mononuclear cells (PBMCs) respond to altered physiological conditions to alleviate the threat. Production of the 70 kDa heat shock protein (HSP70) is up-regulated to protect proteins from degradation. Sequestosome-1 (p62) binds to altered proteins and the p62-protein complex is degraded by autophagy. P62 is also a regulator of intracellular kinase activity and cell differentiation. We hypothesized that the PBMC response to a malignant breast mass involves elevated production of HSP70 and a decrease in intracellular p62. In this study 46 women had their breast mass excised. PBMCs were isolated and intracellular levels of HSP70 and p62 were quantitated by ELISA. Differences between women with a benign or malignant breast mass were determined. A breast malignancy was diagnosed in 38 women (82.6%) while 8 had a benign lesion. Mean intracellular HSP70 levels were 79.3 ng/ml in PBMCs from women with a malignant lesion as opposed to 44.2 ng/ml in controls (p = 0.04). The mean PBMC p62 level was 2.3 ng/ml in women with a benign breast lesion as opposed to 0.6 ng/ml in those with breast cancer (p < 0.001). Mean p62 levels were lowest in women with invasive carcinoma and a positive lymph node biopsy when compared to those with in-situ carcinoma or absence of lymphadenopathy, respectively. Intracellular HSP70 and p62 levels in PBMCs differ between women with a malignant or benign breast lesion. These measurements may be of value in the preoperative triage of women with a breast mass.

A Case of SARS-CoV-2 Clinical Relapse after 4 Negative RT-PCR Tests in Greece: Recurrence or Reinfection?

SARS-CoV-2 pandemic is the greatest public health concern of the year 2020. There are several worldwide reports of patients who have managed to recover from SARS-CoV-2 infection with negative PCR test results, that for unknown reasons convert back to positive PCR. We report a case of a patient in our hospital who developed positive PCR test results for SARS-CoV-2, after 4 consecutive results that were negative, along with a full-blown clinical syndrome of SARS-CoV-2 infection.

Thyroid Dysfunction and Atherosclerosis: A Systematic Review.

BACKGROUND/AIM: Thyroid dysfunction, both hypo- and hyperthyroidism, has been associated with cardiovascular disease. The aim of this study was to evaluate the association between thyroid dysfunction and atherosclerosis measured mostly by carotid intima-media thickness, as well as discuss whether L-T4 replacement is able to reverse or slow down the progression of atherosclerosis. MATERIALS AND METHODS: The review was conducted according the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We performed on PubMed a literature search from May 2004 to January 2020, using the search terms 'subclinical hypothyroidism' or 'thyroid disorders' and 'carotid artery', 'carotid intima-media thickness (IMT)', 'levothyroxine', and 'atherosclerosis'. RESULTS: Twenty-six studies were eligible and included in the analysis. Overall, the studies encompassed a total of 36.434 patients included in this review. Most studies indicated a proportional correlation between IMT and thyroid dysfunction. Levothyroxine (L-T4) replacement led to significant decrease of IMT after 1 year in most studies. CONCLUSION: Most studies have concluded that thyroid dysfunction is associated with arterial wall remodeling and, thus, with increased cardiovascular risk. However, the exact mechanistic background of pathological structural changes in the arterial wall is still unsettled. Large randomized controlled studies are required to definitively address the extent to which T4 replacement therapy might benefit patients with subclinical thyroid disorders.

The Clinical Utility and Assessment of Renal Biomarkers in Acute Kidney Injury After Abdominal Endovascular Aneurysm Repair. A Systematic Review.

The widespread adoption of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA) is due to the obvious advantages of the procedure compared to the traditional open repair. However, these advantages have to be weighed against the increased risk of renal dysfunction with EVAR. The evaluation of the perioperative renal function after EVAR has been hampered by the lack of sensitive and specific biochemical markers of acute kidney injury (AKI). The purpose of this study was to summarize all novel renal biomarkers and to evaluate their clinical utility for the assessment of the kidney function after EVAR. A systematic review of the current literature, as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines, was performed to identify relevant studies with novel renal biomarkers and EVAR. Pubmed and Scopus databases were systemically searched. Studies reporting on thoracic endovascular aortic repair (TEVAR), case reports, case series, letters to the editor, and systematic reviews were excluded. Neutrophil-Gelatinase-Associated Lipocalin, Cystatin C, Liver-type fatty-acid-binding protein were the most common among the eligible studies while Interleukin-18, Retinol binding protein, N-acetyle-b-D-glucosaminidase and microalbumin have a sparse appearance in the literature. These biomarkers have been assessed in plasma as well as urine samples with each sample material having its own advantages and drawbacks. Which of these biomarkers has the most potential for assessing postoperative renal failure after EVAR, remains to be proved. The few studies presented in the literature show the potential clinical utility of these biomarkers, but larger studies with longer follow-up are required to determine the precise relationship between these biomarkers and postoperative acute kidney injury.

Contemporary Strategies in the Management of Civilian Abdominal Vascular Trauma.

The evaluation and management of patients with abdominal vascular trauma or injury requires immediate and effective decision-making in these unfavorable circumstances. The majority of these patients arrive at trauma centers in profound shock, secondary to massive blood loss, which is often unrelenting. Moreover, ischemia, compartment syndrome, thrombosis, and embolization may also be life threatening and require immediate intervention. To minimize the risk of these potentially lethal complications, early understanding of the disease process and emergent therapeutic intervention are necessary. In the literature, the management of acute traumatic vascular injuries is restricted to traditional open surgical techniques. However, in penetrating injuries surgeons often face a potentially contaminated field, which renders the placement of prosthetic grafts inappropriate. Currently, however, there are sparse data on the management of vascular trauma with endovascular techniques. The role of endovascular technique in penetrating abdominal vascular trauma, which is almost always associated with severe active bleeding, is limited. It is worth mentioning that hybrid operating rooms with angiographic radiology capabilities offer more opportunities for the management of this kind of injuries by either temporary control of the devastating bleeding using endovascular balloon tamponade or with embolization and stenting. On the other hand, blunt abdominal injuries are less dangerous and they could be treated at most times by endovascular means. Since surgeons continue to encounter abdominal vascular trauma, open and endovascular techniques will evolve constantly giving us encouraging messages for the near future.

Apolipoprotein J as a predictive biomarker for restenosis after carotid endarterectomy: a retrospective study.

Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis in most patients. Restenosis after CEA can lead to re-intervention and adverse events, but the factors predicting restenosis are poorly understood. Apolipoprotein J (ApoJ) is considered to be a novel predictive factor of vascular restenosis and is associated with a large number of processes related to atherosclerosis and cell-cycle phases. The aim of this study was to elucidate the predictive value of Apo J in internal carotid artery (ICA) restenosis following CEA. This retrospective study examined all prospectively collected data for patients who underwent CEA at our surgical department over a 2-year period. The serum ApoJ levels of 100 patients were examined; 56 patients who underwent CEA comprised the vascular group (VG), and 44 patients who underwent minor surgery comprised the control group (CG). ApoJ samples were obtained preoperatively, 24 h after the surgical procedure and at 1, 6 and 12 months thereafter during the follow-up. The preoperative difference in ApoJ levels between the CG and VG was statistically signifcant; the mean values were 39.11±14.16 and 83.03±35.35 µg/mL, respectively. In the VG, the serum ApoJ levels were 112.09±54.40, 71.20±23.70, 69.92±25.76 and 62.25±19.17 µg/mL at postoperative day 1 and at 1, 6 and 12 months post-operatively, respectively, while the ApoJ concentrations of patients in the CG remained unchanged. Further subdivision of the VG into patients with or without restenosis revealed that restenosis patients presented signifcantly higher mean ApoJ values than non-restenosis VG patients. In summary, ApoJ seems to be an important predictor for carotid restenosis at 6 and 12 months postoperatively.

Stenting of Subclavian Artery True and False Aneurysms: A Systematic Review.

BACKGROUND: Aneurysms of the subclavian artery are usually the result of trauma, atherosclerosis, or thoracic outlet syndrome. Until the 90s, open surgical repair was considered the only therapeutic choice, exhibiting high complication rates. Since the first report of endovascular repair of subclavian aneurysms in 1991, promising results have been published. The aim of this review was to summarize all available data on subclavian artery (SA) true and false aneurysm stenting to reach conclusions regarding morbidity, mortality, and other procedure-related characteristics. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Eligible studies were sought in the Medline (PubMed), ClinicalTrials.gov, and Cochrane library-Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 2017 using the following MeSH terms: "endovascular", "hybrid", "aneurysm", "pseudo-aneurysm", "pseudo-aneurysm", "false aneurysm", "arterial injury", "subclavian artery", "axillo-subclavian," and "axillosubclavian artery". The reference lists of eligible articles and pertinent reviews were screened for potential relevant studies. RESULTS: Seventy-three studies encompassing data on 142 patients who underwent endovascular or hybrid SA aneurysm repair were deemed eligible. One hundred forty-seven stents and stent grafts were used. Median age of all patients was 56 years, and males comprised 46% of the study sample. Trauma was the most common mechanism of injury. Pulsatile mass or hematoma was the most frequent presenting sign. Pseudoaneurysms were the most frequent type of aneurysms, followed by true aneurysms. Most authors used self-expanding polytetrafluoroethylene-covered stents. Access was obtained by either brachial, femoral, or both arteries. Through-and-through technique was also used in angulated vessels. All-cause mortality was 10.6%, slightly higher to that already reported in literature and lower to the respective rate of the open repair. Reintervention rate was 8.5% despite the high 15.5% complication rate. CONCLUSIONS: Endovascular SA aneurysm repair is a technically feasible technique, useful in both elective and emergency cases. Although preliminary results quote its safety and efficacy, larger cohort studies are warranted to elucidate its benefit in treating SA aneurysms.

Serum Calprotectin as a Novel Biomarker in Abdominal Aortic Aneurysm Pathogenesis and Progression: Preliminary Data from Experimental Model in Rats.

BACKGROUND: Abdominal aortic aneurysm (AAA) formation is associated with by inflammation and matrix degradation. This study tested the hypothesis that calprotectin, a novel biomarker for inflammation, as well as established biomarkers such as C-reactive protein (CRP) and matrix metalloproteinase- 9 (MMP-9) could also be indicative inflammatory biomarkers during AAA pathogenesis and progression. We also evaluated the correlation of serum soluble Receptor for Advanced Glycation End Products (sRAGE) with AAA diameter and serum calprotectin levels. MATERIALS AND METHODS: Rat abdominal aortas were perfused with porcine pancreatic elastase (AAA Group) or saline (Control Group) and studied on post-perfusion days 7 and 14 (n=11 per treatment group). Aneurysm was defined as a dilatation of the aorta above 150% of its original diameter. Laparotomy was performed on days 0 (T0), 7 (T7) and 14 (T14) for aortic diameter measurement. At the same time intervals, we measured the serum levels of calprotectin, CRP, sRAGE and MMP-9. RESULTS: All animals developed AAA and no rupture occurred. MMP-9 in AAA group at T14 (p<0.05 compared with T7 and p<0.005 compared with T0) and calprotectin in AAA group at T14 (p<0.001 compared with T7 and T0) continued to significantly increase at all times. Serum sRAGE was significantly lower in the AAA group compared with the control group and within AAA group at all time points (p<0.001). On the other hand, the highest levels of CRP were identified at T7 in both groups. Calprotectin concentrations in AAA group were significantly higher compared with controls at T7 and T14 (p<0.001 and p<0.001, respectively). Aortic diameter was significantly correlated with MMP-9 and calprotectin serum concentrations at all time points (r=0.51, p<0.001; r=0.728, p<0.001 respectively). Serum sRAGE levels were significantly correlated with aortic diameter at all time points (r=-0.48, p<0.001) and serum calprotectin levels (r=-0.22, p<0.001). CONCLUSION: This is the first evaluation of calprotectin as an AAA inflammation biomarker. It seems to be a promising marker related to AAA natural history. Further experimental and large human studies are needed to fully elucidate the role of calprotectin in the development and progression of AAAs.

Contemporary Strategies in the Management of Civilian Neck Zone II Vascular Trauma.

Neck trauma is the leading cause of death mainly in younger persons posing to surgeons the dilemma whether to proceed with reconstruction of vascular injuries either in the presence of coma or in severe neurological deficit. Vascular injuries in zone II predominate over the other injuries located in zones I/III of the neck. Conventional open repair of carotid injuries with primary closure or interposition grafting is always recommended due to the effective long-term results for penetrating injuries or for patients unfit for endovascular intervention. In cases of blunt trauma, anticoagulation or antiplatelet therapy should be administered first in neurologically stable patients. In case of worsening of the neurological status of the patient despite adequate anticoagulation endovascular means should be considered in cases of appropriate anatomy of the arterial trauma. We provide an update on penetrating/blunt trauma in zone II of the neck, giving emphasis on the anticoagulant and endovascular treatment.

A critical reappraisal of the treatment modalities of normal appearing thoracic aorta mural thrombi.

Mural thrombus in non-atherosclerotic or aneurysmatic thoracic aorta is a relatively uncommon entity. Currently there is no consensus on the appropriate therapeutic algorithm of its management. We aim to present the current knowledge on the treatment of thoracic aorta mural thrombi (TAMT) in minimally atherosclerotic vessels and we hope that the juxtaposed discussions will shed light on the uncharted waters regarding this rare syndrome. The MEDLINE/PubMed database was searched for publications with the medical subject "aortic mural thrombus" and keywords "thoracic", "embolism", "normal vessel", "minimally atherosclerotic vessel" or "treatment". We restricted our search to English language, till January 2017. The electronic literature search yielded 23 reports that were deemed appropriate for further analysis. Anticoagulation is the standard of care for the treatment of the thrombus whereas surgical and interventional treatment seems to be related with increased mortality and lower recurrence rates. TAMT treatment is controversial. Anticoagulants are the mainstay of treatment but surgery seems to gain ground in several settings as an only therapy or a combined treatment modality. More data are needed on the role of novel oral anticoagulants and endografts.

Comprehensive Surgical Treatment as the Mainstay of Management in Retroperitoneal Sarcomas: Retrospective Study from Two Non-sarcoma Specialist Centers.

BACKGROUND/AIM: Complete resection, surgical expertise and individualization of patient management in comprehensive oncology centres result in better clinical outcomes in patients presenting with retroperitoneal sarcomas. PATIENTS AND METHODS: Clinical outcomes of primary and recurrent retroperitoneal sarcoma resections performed between January 2002 and December 2016 in two large surgical oncology, but non-sarcoma specialist centers, were reviewed to determine the efficacy of complete surgical resection as the principle instrument for treatment. The histological type, tumor size and grade, as well as organ resection, were recorded and subsequently reviewed. RESULTS: Our study included 108 cases of sarcoma resection (60 first-time, 38 second-time and 10 third-time laparotomies) in 60 patients (35 males and 25 females). Most patients had complete resection: 57 had a macroscopically complete (R0/R1) resection and three had R2 resection. The 90-day mortality rate was zero and morbidity was minimal. Five- and 10-year overall survival (OS) rates were 88% and 79%, respectively, whereas the corresponding disease-free survival (DFS) rates were 65% and 59%, respectively. High-grade tumors were associated with decreased DFS (hazard ratio(HR)=3.35; 95% confidence interval(CI)=1.23-9.10; p=0.018) and decreased OS (HR=7.18; 95% CI=1.50-34.22; p=0.013). CONCLUSION: Complete surgical resection of retroperitoneal sarcomas combined with individualized patient management when offered by experienced surgical oncology teams, adhering to international guidelines, can succeed in providing patients with good long-term outcomes, comparable to those achieved at sarcoma-specialist centers.

Thoracic Aorta Aneurysm Repair in a Patient with a Solitary Kidney: Hybrid Surgery as a Bailout Procedure.

Thoracic endovascular aortic repair (TEVAR) is an emerging treatment option for thoracic aorta aneurysms (TAA). Endovascular access is a challenge. We present a novel TEVAR technique in a patient with single kidney and a 6.4 cm TAA. Attempting to place a sheath through iliac arteries was unsuccessful. The decision to proceed to hybrid TEVAR was made. The protection of the solitary kidney was achieved through axillo-femoral bypass, followed by an end-to-side anastomosis between the aorta and a bifurcated graft. Through the graft, a stent was introduced in the thoracic aorta. With the use of contrast material, the right position of the graft was confirmed.

Neutrophil Gelatinase Associated Lipocalin (NGAL) as a Biomarker. Does It Apply in Abdominal Aortic Aneurysms? A Review of Literature.

Neutrophil gelatinase associated lipocalin (NGAL) as a protein derived from neutrophils has recently been the field of investigation in a wide range of diseases (renal disease, coronary artery disease, etc). The MEDLINE/PubMed database was searched for publications with the medical subject heading "NGAL" and keywords "Abdominal aortic aneurysm (AAA)," "biomarker," and "growth". We restricted our search to date. In this review, we included 38 articles and abstracts that were accessible and available in English. An effort to further explain the role of NGAL within AAA has been made. NGAL seems to be a hopeful marker for the pathogenesis and the progression of abdominal aortic aneurysms (AAAs), which has significant morbidity and mortality rates.