Salivary gland regeneration: from salivary gland stem cells to three-dimensional bioprinting.

Hyposalivation and severe dry mouth syndrome are the most common complications in patients with head and neck cancer (HNC) after receiving radiation therapy. Conventional treatment for hyposalivation relies on the use of sialogogues such as pilocarpine; however, their efficacy is constrained by the limited number of remnant acinar cells after radiation. After radiotherapy, the salivary gland (SG) secretory parenchyma is largely destroyed, and due to the reduced stem cell niche, this gland has poor regenerative potential. To tackle this, researchers must be able to generate highly complex cellularized 3D constructs for clinical transplantation via technologies, including those that involve bioprinting of cells and biomaterials. A potential stem cell source with promising clinical outcomes to reserve dry mouth is adipose mesenchymal stem cells (AdMSC). MSC-like cells like human dental pulp stem cells (hDPSC) have been tested in novel magnetic bioprinting platforms using nanoparticles that can bind cell membranes by electrostatic interaction, as well as their paracrine signals arising from extracellular vesicles. Both magnetized cells and their secretome cues were found to increase epithelial and neuronal growth of in vitro and ex vivo irradiated SG models. Interestingly, these magnetic bioprinting platforms can be applied as a high-throughput drug screening system due to the consistency in structure and functions of their organoids. Recently, exogenous decellularized porcine ECM was added to this magnetic platform to stimulate an ideal environment for cell tethering, proliferation, and/or differentiation. The combination of these SG tissue biofabrication strategies will promptly allow for in vitro organoid formation and establishment of cellular senescent organoids for aging models, but challenges remain in terms of epithelial polarization and lumen formation for unidirectional fluid flow. Current magnetic bioprinting nanotechnologies can provide promising functional and aging features to in vitro craniofacial exocrine gland organoids, which can be utilized for novel drug discovery and/or clinical transplantation.

Biofabrication, biochemical profiling, and in vitro applications of salivary gland decellularized matrices via magnetic bioassembly platforms.

Trending three-dimensional tissue engineering platforms developed via biofabrication and bioprinting of exocrine glands are on the rise due to a commitment to organogenesis principles. Nevertheless, a proper extracellular matrix (ECM) microarchitecture to harbor primary cells is yet to be established towards human salivary gland (SG) organogenesis. By using porcine submandibular gland (SMG) biopsies as a proof-of-concept to mimic the human SG, a new decellularized ECM bioassembly platform was developed herein with varying perfusions of sodium dodecyl sulfate (SDS) to limit denaturing events and ensure proper preservation of the native ECM biochemical niche. Porcine SMG biopsies were perfused with 0.01%, 0.1%, and 1% SDS and bio-assembled magnetically in porous polycarbonate track-etched (PCTE) membrane. Double-stranded DNA (dsDNA), cell removal efficiency, and ECM biochemical contents were analyzed. SDS at 0.1% and 1% efficiently removed dsDNA (< 50 ng/mg) and preserved key matrix components (sulfated glycosaminoglycans, collagens, elastin) and the microarchitecture of native SMG ECM. Bio-assembled SMG decellularized ECM (dECM) perfused with 0.1-1% SDS enhanced cell viability, proliferation, expansion confluency rates, and tethering of primary SMG cells during 7 culture days. Perfusion with 1% SDS promoted greater cell proliferation rates while 0.1% SDS supported higher acinar epithelial expression when compared to basement membrane extract and other substrates. Thus, this dECM magnetic bioassembly strategy was effective for decellularization while retaining the original ECM biochemical niche and promoting SMG cell proliferation, expansion, differentiation, and tethering. Altogether, these outcomes pave the way towards the recellularization of this novel SMG dECM in future in vitro and in vivo applications.

Coronary computed tomography angiography following robotic coronary artery bypass grafting surgery: Systematic approach to image analysis and practical considerations.

Standard open chest Coronary Artery Bypass Grafting (CABG) has evolved over last couple of decades. With advancement in minimally invasive procedures, Robotic CABG (RCABG) is still in its evolution phase. There is dearth of experienced surgeons in this complicated field and lack of data to verify it clinical safety. in this review, we intend to describe the utility of Cardiac Computed Tomography Angiography (CCTA) in assessment of graft anatomy and quality, grafting strategy, distal graft anastomosis site evaluation and detection of complications associated with RCABG. CCTA appears to provide valuable information regarding the visualization of grafts, target coronary arteries and other cardiac and non-cardiac structures.

Postoperative Atypical Hemolytic Uremic Syndrome in a 67-Year-Old Woman Associated with Hemolytic Anemia, Thrombocytopenia, and Acute Renal Failure.

BACKGROUND Hemolytic uremic syndrome (HUS) develops from uncontrolled complement activation leading to intravascular hemolysis and thrombotic microangiopathy. Atypical HUS is diagnosed by excluding a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13 deficiency, and infection-associated HUS. Patients with atypical HUS may respond to eculizumab. We present a case of a 67-year-old woman who developed atypical HUS with hemolytic anemia, renal failure, and thrombocytopenia following an elective hip arthroplasty. CASE REPORT An otherwise healthy 67-year-old woman was admitted to our hospital after an elective right total hip arthroplasty. In the postoperative course, she developed vomiting and acute renal failure that was initially attributed to a prerenal cause. She continued to have worsened renal failure in spite of intravenous hydration, and she also developed mild thrombocytopenia. A peripheral blood smear was performed and showed the presence of schistocytes (red blood cell fragments) consistent with microangiopathic hemolytic anemia. In the context of anemia, thrombocytopenia, and renal failure, this finding led to a prompt and early referral to a tertiary care center and a timely diagnosis of atypical HUS. The patient underwent treatment with plasmapheresis, hemodialysis, and eculizumab. CONCLUSIONS This report highlights the importance of examination of the peripheral blood smear in the diagnosis of thrombotic microangiopathy. As shown in our case, the presence of schistocytes indicates the need for prompt clinical management.

Plant growth promoting rhizobacteria alleviates drought stress in potato in response to suppressive oxidative stress and antioxidant enzymes activities.

Maintenance of plant physiological functions under drought stress is normally considered a positive feature as it indicates sustained plant health and growth. This study was conducted to investigate whether plant growth-promoting rhizobacteria (PGPR) Bacillus subtilis HAS31 has potential to maintain potato growth and yield under drought stress. We analyzed trends of chlorophyll concentration, photosynthesis process, relative water content, osmolytes, antioxidants enzymes and oxidative stress, relative growth rate, tuber and aboveground biomass production in two potato varieties, Santae (drought-tolerant) and PRI-Red (drought-sensitive). Plants of both genotypes were treated with 100 g of HAS31 inoculant at 10 days after germination and exposed to different soil relative water contents (SRWC), including 80 ± 5% (well watered), 60 ± 5% (moderate stress) and 40 ± 5% SRWC (severe stress) for 7 days at tuber initiation stage (30 days after germination). The drought stress reduced plant relative growth rate, biomass production, leaf area, number of leaves and tubers, tuber weight, and final yield. The drought-stressed plants showed decline in chlorophyll contents, membrane stability, leaf relative water contents and photosynthetic rate. Under drought stress, enzymatic activity of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD), contents of total soluble sugars, soluble proteins and proline increased. The application of PGPR reduced the impact of drought and maintained higher growth and physio-chemical traits of the plants. The plants with PGPR application showed higher relative growth rate, dry matter production, leaf area, number of tubers, tuber weight and yield as compared to plants without PGPR. The PGPR-HAS31 treated plants maintained higher photosynthetic process, contents of chlorophyll, soluble proteins, total soluble sugars, and enzymatic activities of CAT, POD and SOD as compared to plants without PGPR. The results of the study suggest that plant growth regulators have ability to sustain growth and yield of potato under drought stress by maintaining physiological functions of the plants.

A systematic review and meta-analysis of endovascular versus open surgical revascularization for chronic mesenteric ischemia.

BACKGROUND: Despite the enthusiasm for endovascular revascularization for chronic mesenteric ischemia (CMI), it is not clear if early benefits offset long-term patency rates. This systematic review aimed to provide an up-to-date comprehensive evidence synthesis evaluating the two approaches. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through July 15, 2016, for studies that compared the endovascular with the open surgical approach for revascularization in CMI patients. We conducted a random-effects meta-analysis to pool outcomes of interest across studies. RESULTS: We included 100 observational studies (22 comparative, 78 noncomparative; 18,726 patients; mean age, 69 years). Open surgery was associated with a statistically significant increase in the risk of in-hospital complications (relative risk [RR], 2.2; 95% confidence interval [CI], 1.8-2.6) and a nonsignificant increase in mortality at 30 days (RR, 1.57; 95% CI, 0.84-2.93). Open surgery was associated with lower risk of 3-year recurrence rates (RR, 0.47; 95% CI, 0.34-0.66) and a similar 3-year survival. Data from noncomparative studies provided similar inferences. The quality of evidence was low. CONCLUSIONS: Observational evidence suggests that the endovascular approach for revascularization in patients with CMI may offer better early outcomes than open surgery, although this effect may not be durable. Long-term mortality appears to be similar.

Fungal Endocarditis: Update on Diagnosis and Management.

Fungal endocarditis is an extremely debilitating disease associated with high morbidity and mortality. Candida spp. are the most common isolated organisms in fungal endocarditis. It is most prevalent in patients who are immunosuppressed and intravenous drug users. Most patients present with constitutional symptoms, which are indistinguishable from bacterial endocarditis, hence a high index of suspicion is required for pursuing diagnosis. Diagnosis of fungal endocarditis can be very challenging: most of the time, blood cultures are negative or take a long time to yield growth. Fungal endocarditis mandates an aggressive treatment strategy. A medical and surgical combined approach is the cornerstone of therapy.

A Novel Way of Treating Multidrug-resistant Enterococci.

CONTEXT: Daptomycin is the only antibiotic available with in vitro bactericidal activity against vancomycin-resistant enterococci (VRE). Its increased use has resulted in cases of decreased daptomycin efficacy. Recent in vitro studies have shown effective use of beta (ß)-lactam and daptomycin antibiotics, as a combination therapy, in the treatment of VRE. We describe a case of effective treatment in a patient with VRE infection using dual ampicillin and daptomycin therapy that shows bench-to-bedside application of the abovementioned finding. CASE REPORT: A 76-year-old gentleman with a history of bilateral arthroplasty was admitted with a swollen left knee. Blood cultures were positive for Enterococcus faecium. Left knee joint aspiration showed leukocytosis and alpha defensins. Extensive imaging did not show any other source of infection. Culture sensitivity results showed multidrug-resistant enterococci sensitive to daptomycin. The patient was started on intravenous (IV) daptomycin. His left knee prosthesis was explanted and a spacer was placed. The patient continued to be bacteremic for 10 days after removing the knee prosthesis. The patient was trialed on combination IV ampicillin and daptomycin. His blood culture turned negative 2 days later. The patient was discharged home to continue 6 weeks of IV ampicillin and daptomycin. CONCLUSION: The exact mechanism of the daptomycin/ampicillin synergy effect is unclear. Current hypothesis suggests that ampicillin causes a reduction in the net positive charge of the bacterial surface, possibly by releasing lipoteichoic acid (LTA) from the cell wall. This process increases the ability of the cationic daptomycin/calcium complex to bind to the cell wall more effectively. Our case shows the clinical application of the same. A prospective randomized control trial to explore the effectiveness of dual antibiotic therapy in vivo is needed. If proven, daptomycin/ß-lactam can become a standard of care to treat VRE and decrease daptomycin nonsusceptibility.

Acute Severe Aortic Regurgitation: Imaging with Pathological Correlation.

CONTEXT: Acute aortic regurgitation (AR) is an important finding associated with a wide variety of disease processes. Its timely diagnosis is of utmost importance. Delay in diagnosis could prove fatal. CASE REPORT: We describe a case of acute severe AR that was timely diagnosed using real time three-dimensional (3D) transesophageal echocardiogram (3D TEE). Not only did it diagnose but also the images obtained by 3D TEE clearly matched with the pathologic specimen. Using this sophisticated imaging modality that is mostly available at the tertiary centers helped in the timely diagnosis, which lead to the optimal management saving his life. CONCLUSION: Echocardiography and especially 3D TEE can diagnose AR very accurately. Surgical intervention is the definitive treatment but medical therapy is utilized to stabilize the patient initially.

Feasibility and performance of an adaptive contrast-oriented FDG PET/CT quantification technique for global disease assessment of malignant pleural mesothelioma and a brief review of the literature.

OBJECTIVE: Treatment of malignant pleural mesothelioma (MPM) remains very challenging. Assessment of response to treatment is necessary for modifying treatment and using new drugs. Global disease assessment (GDA) by implementing image processing methods to extract more information out of positron emission tomography (PET) images may provide reliable information. In this study we show the feasibility of this method of semi-quantification in patients with mesothelioma, and compare it with the conventional methods. We also present a review of the literature about this topic. METHODS: Nineteen subjects with histologically proven MPM who had undergone fluoride-18-fluorodeoxyglucose PET/computed tomography ((18)F-FDG PET/CT) before and after treatment were included in this study. An adaptive contrast-oriented thresholding algorithm was used for the image analysis and semi-quantification. Metabolic tumor volume (MTV), maximum and mean standardized uptake volume (SUVmax, SUVmean) and total lesion glycolysis (TLG) were calculated for each region of interest. The global tumor glycolysis (GTG) was obtained by summing up all TLG. Treatment response was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) criteria and the changes of GTG. Agreement between global disease assessment and conventional method was also determined. RESULTS: In patients with progressive disease based on EORTC criteria, GTG showed an increase of 150.7 but in patients with stable or partial response, GTG showed a decrease of 433.1. The SUVmax of patients before treatment was 5.95 (SD: 2.93) and after the treatment it increased to 6.38 (SD: 3.19). Overall concordance of conventional method with GDA method was 57%. Concordance of progression of disease based on conventional method was 44%, stable disease was 85% and partial response was 33%. Discordance was 55%, 14% and 66%. CONCLUSIONS: Adaptive contrast-oriented thresholding algorithm is a promising method to quantify the whole tumor glycolysis in patients with mesothelioma. We are able to assess the total metabolic lesion volume, lesion glycolysis, SUVmax, tumor SUVmean and GTG for this particular tumor. Also we were able to demonstrate the potential use of this technique in the monitoring of treatment response. More studies comparing this technique with conventional and other global disease assessment methods are needed in order to clarify its role in the assessment of treatment response and prognosis of these patients.

Left ventricular lead positioning in cardiac resynchronization therapy: an innovative retrograde approach without using snare.

AIMS: Ideal positioning of left ventricular (LV) pacing lead in cardiac resynchronization therapy (CRT) is technically demanding. This case aims to place LV lead in anterolateral branch of coronary sinus (CS) using collateral route blindly. METHODS AND RESULTS: Externalization via the CS ostium using collaterals retrogrogradely, which was not visible in initial balloon occlusion venography, through one delivery sheath with the support of commonly used micro-guide catheter and subsequent successful LV lead placement in anterolateral branch of CS. CONCLUSION: This innovative retrograde approach for LV pacing lead implantation in anterolateral branch of CS obviated the need for snare technique to capture the distal end of the wire when antegrade route was not successful.

Device sizing for transcatheter closure of ruptured sinus of Valsalva as per echocardiography color Doppler turbulent flow jet diameter.

Rupture of sinus of Valsalva (SV) is a rare occurrence with a wide spectrum of presentation, ranging from an asymptomatic murmur to cardiogenic shock or even sudden cardiac death. We hereby report a case which was successfully closed by transcatheter technique. In this case, ruptured SV was entered from the aorta, an arteriovenous loop was created and device was implanted using a venous approach. The procedure was safe, effective and uncomplicated, obviating the need for surgery. In this case, the authors report for the first time the use of echo color Doppler turbulent flow jet diameter as a reference value for sizing the device.

Symptomatic radial artery thrombosis successfully treated with endovascular approach via femoral access route.

Radial access has been increasingly utilized for coronary intervention due to higher safety profile in comparison to femoral access site with lower bleeding rate. Radial artery occlusion is not uncommon with radial access site. This usually does not lead to any harm due to ulnar artery collaterals that are sufficient to prevent hand ischemia and is usually left alone. However, in the case of significant hand ischemia, treatment is often necessary. We are reporting an interesting case of symptomatic radial artery thrombosis leading to arm ischemia that was successfully treated percutaneously using femoral access. Using femoral access for radial artery intervention has not been reported previously. This case is followed by review of the literature.

Comparison of zotarolimus- and everolimus-eluting stents in patients with ST-elevation myocardial infarction and chronic kidney disease undergoing primary percutaneous coronary intervention.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor outcomes after percutaneous coronary intervention (PCI). The aim of the study was to compare zotarolimus- and everolimus-eluting stents used during primary PCI in patients with acute myocardial infarction (AMI) and CKD. METHODS: We selected 854 consecutive ST-elevation MI patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) undergoing primary PCI who were followed up for 12 months. They were divided into two groups based on type of stents implanted: (1) zotarolimus-eluting stent (ZES) and (2) everolimus-eluting stent (EES). The study end point was the 12-month major adverse cardiac events (MACE) which included all-cause death, non-fatal MI, target lesion revascularization (TLR), and target vessel revascularization (TVR). RESULTS: The average number of stents used per vessel was 1.4 ± 0.7. A total of 433 patients received ZES and 421 patients received EES. There was no significant difference in the incidence of 12-month MI, TLR, or TVR. All-cause death was found to be borderline significant between two groups (2.8% in ZES vs 0.9% in EES, p=0.05). The incidence of 12-month MACE in ZES and EES was 5.7% and 2.6% respectively, p=0.022. Stent thrombosis did not differ between groups (p=0.677). Kaplan-Meier analysis did not show significant difference for 12-month MACE-free survival between groups (log-rank p=0.158). It remained the same even after propensity adjustment for multiple confounders in Cox model (p=0.326). CONCLUSIONS: Implantation of ZES or EES provided comparable clinical outcomes with similar risk of 12-month MACE and death in STEMI patients with CKD undergoing primary PCI.

Simple mechanical thrombectomy with intrapulmonary arterial thrombolysis in pulmonary thromboembolism: a small case series.

Pulmonary thromboembolism (PTE) is a life-threatening condition with a high early mortality rate caused by acute right ventricular failure and cardiogenic shock. We report a series of three patients who presented with acute and subacute submassive PTE. They were successfully treated by simple catheter-based mechanical thrombectomy and intrapulmonary arterial thrombolysis. Mechanical fragmentation and aspiration of thrombus was performed by commonly used J-wire, multi-purpose and Judkin Right guiding catheters and this obviated the need of specific thrombectomy devices.

Simple mechanical thrombectomy with intrapulmonary arterial thrombolysis in pulmonary thromboembolism:a small case series / 老年心脏病学杂志（英文版）

Pulmonary thromboembolism (PTE) is a life-threatening condition with a high early mortality rate caused by acute right ventricular failure and cardiogenic shock. We report a series of three patients who presented with acute and subacute submassive PTE. They were suc-cessfully treated by simple catheter-based mechanical thrombectomy and intrapulmonary arterial thrombolysis. Mechanical fragmentation and aspiration of thrombus was performed by commonly used J-wire, multi-purpose and Judkin Right guiding catheters and this obviated the need of specific thrombectomy devices.

Positive remodeling is associated with vulnerable coronary plaque components regardless of clinical presentation: virtual histology-intravascular ultrasound analysis.

OBJECTIVE: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between coronary artery remodeling pattern and plaque components in 1133 patients. METHODS: We divided the patients into two groups according to the remodeling pattern as positive remodeling (PR, remodeling index>1.05) (n=192) and intermediate remodeling (IR, remodeling index ≤ 1.05 and ≥ 0.95)/negative remodeling (NR, remodeling index<0.95) (n=941). VH-IVUS analysis classified the color-coded tissue into four major components: green (fibrotic, FT); yellow-green (fibro-fatty); white (dense calcium); and red (necrotic core, NC). Thin-cap fibroatheroma (TCFA) was defined as focal, NC-rich (≥ 10% of the cross-sectional area) plaques being in contact with the lumen in a plaque burden ≥ 40%. RESULTS: At the minimum lumen site, PR group had greater plaque plus media area (12.8 ± 4.9 vs. 9.9 ± 3.8mm(2), p<0.001) and greater %NC area (21.7 ± 12.3 vs. 18.2 ± 11.6%, p<0.001) and smaller %FT area (57.0 ± 14.5 vs. 59.4 ± 14.6%, p=0.037) compared with IR/NR group. PR group had greater plaque volume (188 ± 150 vs. 135 ± 130 mm(3), p<0.001) and greater %NC volume (19.1 ± 9.6 vs. 16.6 ± 9.2%, p=0.001) and smaller %FT volume (58.3 ± 11.7 vs. 60.6 ± 11.0%, p=0.009) compared with IR/NR group. PR group had more TCFA compared with IR/NR group (21% vs. 13%, p=0.006). Similar findings about plaque components were observed in terms of greater %NC volume and smaller %FT volume in PR group compared with IR/NR group in patients with both acute coronary syndrome and stable angina. CONCLUSIONS: VH-IVUS analysis demonstrates that PR was associated with more vulnerable plaque components compared with IR/NR regardless of their clinical presentation.