Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

Clinical and molecular insights into BCG immunotherapy for melanoma.

The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette-Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. Intralesional BCG (IL-BCG) immunotherapy is a highly efficient and cost-effective treatment option for inoperable stage III in-transit melanoma, as recommended in the National Comprehensive Cancer Network Guidelines. IL-BCG has shown great efficacy in the regression of directly injected metastatic melanoma lesions, as well as distal noninjected nodules in immunocompetent patients. Clinical and preclinical studies have shown that BCG serves as a strong immune modulator, inducing the recruitment of various immune cells that contribute to antitumour immunity. However, the specific mechanism of BCG-mediated tumour immunity remains poorly understood. Comparative genome analyses have revealed that different BCG strains exhibit distinct immunological activity and virulence, which might impact the therapeutic response and clinical outcome of patients. In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG-induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.

Seroma prevention strategies in laparoscopic ventral hernia repair: a systematic review.

BACKGROUND: Laparoscopic ventral hernia repair (LVHR) has been increasing in popularity over the years. Seroma formation is a common complication of LVHR. The aim of this study is to review the current evidence on seroma prevention strategies following LVHR. METHODS: A systematic search of PubMed, Embase (1946-13 February 2019) and Medline (1946-13 February 2019) databases was conducted using terms which include "seroma", "hernia, ventral" and "laparoscopy". All studies are comparative retrospective or prospective human adult studies in peer-reviewed journals describing at least one intra-operative intervention designed to decrease the rate of seroma formation in laparoscopic ventral hernia repair. RESULTS: The database searches identified 3762 citations, and 21 studies were included for final analysis. Five studies compared the different methods of mesh fixation, nine studies compared primary defect closure (PFC) and bridged repair, two studies compared the effect of different types of meshes, two studies looked into the use of electrical cauterization, one study compared single- site laparoscopy with conventional laparoscopy, one study looked into the use of fibrin sealant and one study compared transabdominal preperitoneal placement of mesh with conventional repair. PFC appears to be the most promising with large studies showing a low rate of seroma formation with additional benefits of decreasing wound infection and recurrence rate. Cauterisation of hernia sac and injection of fibrin sealant also show promising results but are mainly derived from small studies. Other strategies did not demonstrate benefit. CONCLUSION: Currently, primary fascial closure appears to be the most promising strategy available to decrease seroma formation after LVHR based on the results of large studies. Other promising strategies that decrease dead space such as cauterisation of the sac and fibrin sealant injection will require further multicentre trials to confirm benefit before an increase in operative time and cost can be justified for their routine use.

Base of tongue cancer-is it tongue cancer located at the base of the tongue, or is it a type of lingual tonsil cancer? The perspective from a genomic analysis.

The aim of this study was to determine whether base of tongue (BOT) cancer is tongue cancer located at the base of the tongue or lingual tonsil cancer originating from tonsil tissue. This was a retrospective study using data from The Cancer Genome Atlas (TCGA). The genomic patterns of three primary cancers (BOT, oral tongue, and tonsil) were compared to determine their similarities and differences. Gene expression data (n=193; 26 BOT, 125 oral tongue, and 42 tonsil cases), copy number alteration data (n=142; 19 BOT, 96 oral tongue, and 27 tonsil cases), and somatic mutation data (n=187; 25 BOT, 122 oral tongue, and 40 tonsil cases) were analyzed using the t-test, heatmap analysis, and OncoPrint, respectively. Clinical information for the three tumour groups was included in the analyses. When using multiplatform analysis, BOT cancer showed nearly the same genomic pattern as tonsil cancer, but not oral tongue cancer. The χ2 test and survival analysis revealed that BOT cancer had the same clinical and survival patterns as tonsil cancer. In conclusion, BOT cancer showed a genomic pattern similar to that of tonsil cancer, but different to that of oral tongue cancer. Further prospective studies are warranted before the results of this study can be applied in a clinical setting.

Microfluidic self-assembly of folate-targeted monomolecular siRNA-lipid nanoparticles.

Non-viral delivery of nucleic acids for therapies based on RNA interference requires a rational design and optimal self-assembly strategies. Nucleic acid particles need to be small, stable and functional in terms of selective cell uptake and controlled release of encapsulated nucleic acids. Here we report on small (∼38 nm) monomolecular nucleic acid/lipid particles (mNALPs) that contain single molecules of short double-stranded oligonucleotides covered by a tight, highly curved lipid bilayer. The particles consist of DOPE, DOTAP, DOPC and DSPE-PEG(2000) and are assembled with 21 bp double-stranded DNA or small interfering RNA by solvent exchange on a hydrodynamic-focusing microfluidic chip. In comparison to vortex mixing by hand this method increases the encapsulation efficiency by 20%, and yields particles with a narrower size distribution, negligible aggregate formation and high stability in blood plasma and serum. Modification of mNALPs with folate-conjugated PEG-lipids results in specific binding and uptake by epithelial carcinoma KB cells overexpressing folate receptors. Binding is significantly reduced by competitive inhibition using free folate and is not observed with non-targeted mNALPs, revealing high specificity. The functionalized mNALPs show gene silencing in the presence of chloroquine, an endosome-destabilizing agent. Together, the robust self-assembly of small-sized mNALPs with their high stability and receptor-specific cell uptake demonstrate that the tight, PEG-grafted lipid-bilayer encapsulation may offer a promising approach towards the delivery of short double-stranded oligonucleotides.

Association between exposure to household cigarette smoking behavior and cigarette smoking in Hispanic adults: Findings from the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Cigarette smoking behavior is highly determined by social influences during childhood and adolescence. This phenomenon has not been fully evaluated in the Hispanic/Latino population. PURPOSE: To examine the association between exposure to household cigarette smoking behavior (HCSB) and adult cigarette smoking among a diverse Hispanic/Latino population living in four US urban centers. The effect of acculturation on cigarette smoking was also evaluated. METHODS: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n=13,231, ages 18-74years, collected between March 2008 and June 2011) were analyzed using logistic regression. RESULTS: HCSB exposure was an independent risk factor for adult current cigarette smoking in Hispanic/Latinos (OR 1.7; 95% CI 1.4, 2.1) after controlling for relevant confounders including socio-demographic and cultural factors. Cubans and Puerto Ricans had the highest prevalence of HCSB exposure (59% and 47% respectively) and highest prevalence of current cigarette smoking (26% and 32%) compared with other Hispanic/Latino groups, (p<.01). CONCLUSIONS: Our data suggest that exposure to HCSB in Hispanics/Latinos living in the US is an independent predictor of adult cigarette smoking, and this association appears to be strongest in Cubans and Puerto Ricans.

Discrepancy between preoperative MRI evaluation and intraoperative or postoperative pathological findings for the extent of local invasion in maxillary squamous cell carcinoma.

Preoperative radiological evaluation of the extent of local invasion in maxillary squamous cell carcinoma (SCC) is very important in planning curative surgery. The aim of this study was to examine the accuracy of preoperative radiological evaluation with magnetic resonance imaging (MRI) for the extent of local invasion in maxillary SCC. A retrospective study was conducted of 33 patients who underwent a maxillectomy for maxillary SCC. We compared the MRI findings for 18 structures around the maxillary sinus with intraoperative or postoperative pathological findings. Discrepancies were found between preoperative MRI findings and intraoperative or postoperative pathological findings for 22 patients (66.7%). Overall, the specificity, sensitivity, positive predictive value, and negative predictive value of MRI were 83.4%, 83.0%, 64.5%, and 90.4%, respectively. The receiver operating characteristic curve showed that MRI evaluation of the posterolateral structures including the pterygoid plate, pterygoid muscle, and infratemporal fossa had a lower area under the curve (0.614) and a significantly lower accuracy when compared with the other structures (P = 0.294, 95% confidence interval 0.405-0.822). In conclusion, as the accuracy of preoperative MRI evaluation of the posterolateral structures is low, careful evaluation of local extension to the posterolateral structures is needed when planning curative surgery for maxillary SCC.

Trends in colorectal cancer among hispanics by stage and subsite location: 1989-2006.

OBJECTIVES: Hispanic colorectal cancer (CRC) rates historically have been lower than for non-Hispanic Whites in the United States and in Florida. The aim of this study is to understand CRC trends in Florida Hispanics and non-Hispanic Whites. METHODS: Using a cross-sectional study design, all invasive CRCs diagnosed among Florida residents between 1989 and 2006 were accessed from the Florida Cancer Data System (FCDS). These cases were analyzed by Hispanic and non-Hispanic White ethnic identification. The Hispanic Origin Identification Algorithm was applied to the FCDS data to identify Hispanic subjects. Primary cancer site and histology data were organized according to SEER (Surveillance Epidemiology and End Results) categories. Joinpoint regression was used to generate incidence trends by stage and subsite location. RESULTS: Rates of CRC incidence were higher for Florida Hispanics compared with non-Hispanic Whites since the mid 1990s. There was a consistent significant increase in the incidence of distant stage CRC in Hispanics (annual percent change (APC) of 1.26 and 0.90 in males and females), whereas rates in non-Hispanics decreased significantly during the same time period (APC -1.36 and -1.28, respectively). Similar trends were found in distant-stage right-sided CRC. Among right-sided CRCs, local stage incidence rate increased for both non-Hispanic Whites and Hispanics, whereas the incidence rate for regional stage decreased for both racial/ethnic groups. CONCLUSIONS: Trends for distant-stage CRC are increasing among Florida Hispanics. This is a particular public health concern given that CRC is a cancer for which screening modalities exist and could imply a concomitant increase in CRC-related mortality among Florida Hispanics. Lower rates of CRC screening in Hispanics are documented at the state level, relative to non-Hispanic Whites. Screening programs targeting the Florida Hispanic population are warranted.

Outcome of components separation for contaminated complex abdominal wall defects.

BACKGROUND: Contaminated large abdominal wall defects can pose a formidable challenge to the surgeon. This study compared the outcome of components separation (CS) for complex ventral defects with or without contamination. METHODS: A retrospective review was conducted of all patients who underwent CS over an 8-year period. Pre-operative factors such as the presence/absence of contamination were analyzed for their effect on length of hospitalization, readmission rate, post-operative complications, re-intervention rate, and long-term recurrence. RESULTS: A total of 34 patients was analyzed. There were 18 males (53%) with a mean age of 57 years. Mean body mass index was 31 kg/m(2). Seventeen patients (50%) had prior repair (mean 2.1 repairs per patient, median 2). Mean size of abdominal defect was 255 cm(2). Out of the 34 patients, 13 had infected or contaminated defects, including 5 patients with infected mesh. Length of stay was longer in the contaminated group (11.1 vs 3.1 days, P < 0.01). A higher complication rate was noted in the setting of contamination (77 vs 38%, P = 0.03). During a mean follow-up of 47 months, no difference was noted in the re-intervention rate (38 vs 29%, P = 0.70) or long-term recurrence rate of the defect (8 vs 5%, P = 1.0) (contaminated vs non-contaminated group, respectively). CONCLUSIONS: CS is a good option for closure of large contaminated complex abdominal wall defects. Despite an increased risk of postoperative complications and longer hospitalization length, long-term outcomes are favorable.

Defective barrier function in melasma skin.

BACKGROUND: Melasma is characterized by increased pigmentation and photodamaged features, which include solar elastosis. Recently, we detected the downregulation of the genes most associated with lipid metabolism using microarray analysis in melasma. These findings suggested that lesional skin may have different biophysical characteristics, and, in particular, an altered skin barrier function. OBJECTIVE: To determine the cutaneous biophysical characteristics of melasma. METHODS: The melanin index, erythema index, stratum corneum hydration, sebum content and transepidermal water loss (TEWL) were measured for lesional and perilesional normal skin of 16 melasma patients and then compared. In addition, a skin biopsy was performed on 11 of the 16 study subjects to measure stratum corneum thickness and to study the protein expressions of PPAR-α and ALOX15B. RESULTS: Melanin index, erythema index and stratum corneum hydration were significantly higher in lesional skin than in perilesional normal skin. No significant difference was found between lesional and normal skin in terms of basal TEWL level or sebum content. However, the rate of TEWL after barrier perturbation was significantly higher for lesional skin, and the barrier recovery rate was significantly delayed. Furthermore, a trend towards thinned stratum corneum was observed for lesional skin, and this was correlated with barrier recovery rate. The expressions of PPAR-α and ALOX15B were variable in the samples. CONCLUSIONS: Melasma skin is characterized by impaired stratum corneum integrity and a delayed barrier recovery rate.

Elevated LDH and paranasal sinus involvement are risk factors for central nervous system involvement in patients with peripheral T-cell lymphoma.

BACKGROUND: The incidence and risk factors of central nervous system (CNS) involvement in peripheral T-cell lymphomas (PTCLs) are still unclear. PATIENTS AND METHODS: We analyzed 228 patients with PTCLs, excluding cases of extranodal natural killer/T-cell lymphoma and primary cutaneous T-cell lymphoma, by retrospectively collecting the clinical features and outcomes of the patients. RESULTS: Twenty events (8.77%, 20/228) of CNS involvement were observed during a median follow-up period of 13.9 months (range 0.03-159.43). Based on univariate analysis, elevated serum lactate dehydrogenase (LDH) level [P = 0.019, relative risk (RR) 5.904, 95% confidence interval (CI) 1.334-26.123] and involvement of the paranasal sinus (P = 0.032, RR 3.137, 95% CI 1.105-8.908) adversely affect CNS involvement. In multivariate analysis, both were independently poor prognostic factors for CNS relapse [elevated LDH level: P = 0.011, hazard ratio (HR) 6.716, 95% CI 1.548-29.131; involvement of the paranasal sinus: P = 0.008, HR 3.784, 95% CI 1.420-10.083]. The survival duration of patients with CNS involvement was significantly shorter than that of the patients without CNS involvement (P = 0.009), with median overall survival of 7.60 months (95% CI of 4.92-10.28) versus 27.43 months (95% CI of 0.00-57.38), respectively. CONCLUSIONS: Elevated LDH level and involvement of the paranasal sinus are two risk factors for CNS involvement in patients with PTCLs. Considering the poor prognoses after CNS relapse, prophylaxis should be considered with the presence of any risk factor.

High isolation rate of adenovirus serotype 7 from South Korean military recruits with mild acute respiratory disease.

Adenovirus is a major cause of acute respiratory disease (ARD) in military recruits. When South Korean military recruits with ARD were surveyed, adenovirus was identified in 122 (61.0%) of the 200 recruits studied. Moreover, all cases of ARD involving adenovirus were caused by serotype 7.

Spreading dynamics and dynamic contact angle of non-Newtonian fluids.

The spreading dynamics of power-law fluids, both shear-thinning and shear-thickening fluids, that completely or partially wet solid substrate was investigated theoretically and experimentally. An evolution equation for liquid-film thickness was derived using a lubrication approximation, from which the dynamic contact angle versus the contact line moving velocity relationship was evaluated. In the capillary spreading regime, film thickness h is proportional to xi3/(n+2) (xi is the distance from the contact line), whereas in the gravitational regime, h is proportional to xi1/(n+2), relating to the rheological power exponent n. The derived model fit the experimental data well for a shear-thinning fluid (0.2% w/w xanthan solution) or a shear-thickening fluid (7.5% w/w 10 nm silica in polypropylene glycol) on a completely wetted substrate. The derived model was extended using Hoffmann's proposal for partially wetting fluids. Good agreement was also attained between model predictions and the shear-thinning fluid (1% w/w cmc solution) and shear-thickening fluid (10% w/w 15 nm silica) on partially wetted surfaces.

Force of a gas bubble on a foreign particle in front of a freezing interface.

We monitored the formation and development of a single gas bubble on the surface of a spherical particle of size 1.676 mm under unidirectional freezing and thawing (4.6-5.0 microm/s) and for the first time quantitatively estimated the force exerted on this particle by measuring the deformation of an attached elastic stick. The bubble would nucleate and grow on the particle surface closest to the ice front, while the force curve for a freezing-thawing cycle presented a hysteresis characteristic. This force was much greater than in the case without a bubble, and hence it dominated the engulfment process in the present freezing tests. The bubble force increased with increasing bubble size and was shown to be mainly attributable to the elastic force by the deformed bubble shape. Comments were made on the need to incorporate the role of bubbles in predicting the critical velocity to freeze a suspension with high dissolved gas content.

The epidemiology of shoulder dislocations in Malaysia.

The case notes of 102 patients (117 shoulder dislocations) were reviewed retrospectively to improve the understanding of the epidemiology of this common injury. Eighty-one dislocations were primary and 36 dislocations were second or recurrent dislocations. The age distribution was characterized by a peak in male patients aged between 21-30 years. The mean age for males was 30.5 years and 47.7 years for females. The male:female ratio in first time dislocations was 5:2, while it was 5:1 in recurrent dislocations. Ninety-eight percent were anterior dislocations and 2% were posterior dislocations. Greater tuberosity fractures were found in 17 patients and almost half of these patients were aged between 41-50 years. The most common cause of first time dislocation was a direct blow or fall onto the shoulder, accounting for 42 patients (55%). The majority of these patients were aged 40 years and above. Next common cause was motor vehicle accident which occurred mostly in the younger age group. Dislocations due to sporting injuries accounted for only 5.3% of all first time dislocations. Nearly 97% were successfully reduced without a general anaesthesia. Seventy-seven percent of the patients had their shoulders immobilized after reduction, mostly with body strapping only. Fifteen patients (14.7%) were referred for physiotherapy for stiffness. Few operations were performed for recurrent dislocations but surgery does not appear to be well accepted as yet by our patients.