Surgical Controls Research Articles

Mitochondrial changes in platelets are not related to those in skeletal muscle during human septic shock.

Platelets can serve as general markers of mitochondrial (dys)function during several human diseases. Whether this holds true even during sepsis is unknown. Using spectrophotometry, we measured mitochondrial respiratory chain biochemistry in platelets and triceps brachii muscle of thirty patients with septic shock (within 24 hours from admission to Intensive Care) and ten surgical controls (during surgery). Results were expressed relative to citrate synthase (CS) activity, a marker of mitochondrial density. Patients with septic shock had lower nicotinamide adenine dinucleotide dehydrogenase (NADH)/CS (p = 0.015), complex I/CS (p = 0.018), complex I and III/CS (p<0.001) and complex IV/CS (p = 0.012) activities in platelets but higher complex I/CS activity (p = 0.021) in triceps brachii muscle than controls. Overall, NADH/CS (r2 = 0.00; p = 0.683) complex I/CS (r2 = 0.05; p = 0.173), complex I and III/CS (r2 = 0.01; p = 0.485), succinate dehydrogenase (SDH)/CS (r2 = 0.00; p = 0.884), complex II and III/CS (r2 = 0.00; p = 0.927) and complex IV/CS (r2 = 0.00; p = 0.906) activities in platelets were not associated with those in triceps brachii muscle. In conclusion, several respiratory chain enzymes were variably inhibited in platelets, but not in triceps brachii muscle, of patients with septic shock. Sepsis-induced mitochondrial changes in platelets do not reflect those in other organs.

Regulatory mechanisms for the development of the migratory phenotype: Roles for photoperiod and the gonad

This article is part of a Special Issue “Energy Balance”.Male white-crowned sparrows, Zonotrichia leucophrys gambelii, were studied to investigate roles of natural day length and the testes in regulating development and expression of the vernal migration phenotype. Previous work suggested that a pulse of androgen during winter months followed by the vernal increase in photoperiod promotes fueling (fat deposition) to support long distance flight; however, other traits required for successful migration remain untested. To investigate these points, birds were captured on their wintering grounds and castrated prior to winter solstice following Mattocks (1976). A subset of the castrates received 8mm Silastic implants of testosterone (T-castrates) and others blank implants (Blank-castrates) for 16days in February. Shams were surgical controls. Migratory traits measured were as follows: 24h locomotor activity, prenuptial molt, body mass, fat score, flight muscle profile, cloacal protuberance (CPL) and plasma androgens measured over 28weeks divided into 3 experimental periods (pre-implant, implant, and post-implant). Under short day lengths, castration increased diurnal locomotor activity over Shams. Testosterone implants temporarily enhanced CPL, plasma androgens and flight muscle enlargement, but failed to induce migratory restlessness. Whereas all groups exhibited seasonal increases in mass, fat score and muscle profile, only Shams showed timely onset and completion of prenuptial molt and migratory restlessness. Thus, for castrated males exposed to naturally increasing day lengths, the organizational effects of a transient testosterone surge were not sufficient to actuate a timely spring molt and migratory behavior. A fully functional testis that can organize central processes is required for the entire expression of the spring migratory phenotype.

A single administration of dexamethasone may protect tibial plateau cartilage in a mechanically stable surgical model of post traumatic osteoarthritis

Purpose: An acute inflammatory phase follows an injury to the knee joint and initiates a cascade of biochemical events that can contribute to degeneration of the cartilage. Cartilage degeneration after injury is central in the development of posttraumatic osteoarthritis (PTOA) – a debilitating disease that is increasingly affecting active younger individuals. It is currently believed that inflammation following intra-articular bleeding from joint injuries could be a cause in the development of PTOA. To study the effects of inflammation alone within the joint, an injury model was developed in which tissue structures responsible for joint function and stability were not directly impacted. Preliminary evidence in this rabbit model of intra-articular bone injury, intended to simulate posttraumatic hemarthrosis, has shown what appears to be an acute inflammatory phase that resolves after surgery and yet still results in the development of significant PTOA. Therefore, we hypothesize that if insult to the joint increases the expression level of acute inflammatory mediators that expose the cartilage to injury then an intervention that inhibits acute inflammation (dexamethasone) will have positive outcomes on cartilage health within this rabbit bone injury model. Dexamethasone (dex) is a glucocorticoid with potent anti-inflammatory properties that has been widely adopted for clinical use (e.g. in the treatment of rheumatoid arthritis, asthma, and various cancers). Methods: Skeletally mature adult female rabbits aged 52 weeks (n = 18) were used in this study. Six animals were not subjected to any interventions and served as un-operated controls. The remaining 12 were all subjected to a femoral notch drill surgery following the guidelines of our institutional animal care facility. Of this group, six rabbits were treated with one intra-articular injection of Dex (0.5 mg/kg) at the time of surgery. As surgical controls, the remaining 6 animals were subjected to drill surgery, but did not receive any dexamethasone treatment. Animals were sacrificed at 9 weeks post surgery. Histological assessment was completed by two blinded observers using a modified Mankin protocol. qPCR was used to analyze the mRNA levels for select anabolic and catabolic molecules, and values were normalized to 18S mRNA. Kruskal-Wallis with Dunn’s multiple comparisons test were used to investigate treatment group differences (significance accepted at p ≤ 0.05). Results: Histological evaluations (Figure 1A) revealed that at 9 weeks post surgery the cartilage on the tibial plateaus of the drill animals was significantly more damaged than that of the un-operated controls and the animals that received the dex treatment after injury. There were no significant differences between the tibial plateau cartilage of the normal and drill + dex treatment groups, suggesting a positive role for dexamethasone. Furthermore, the mRNA analysis (Figure 1B) revealed that even a single dose of dexamethasone at the time of surgery, was sufficient to attenuate the expression of degradative proteinase matrix metalloproteinase 3 (MMP-3), proteoglycans such as versican and biglycan as well as anabolic marker collagen type II (Col-II) in tibial plateau cartilage. Conclusions: Even in the absence of severe biomechanical changes, the cartilage of the tibial plateau is subject to degeneration in this model. This strongly suggests that initial biological changes are sufficient to drive many of the changes observed within the joint. The results of this study suggest that Dexamethasone treatment given at the time of drill surgery had a positive impact in reducing the degradation of the cartilage covering the tibial plateau. Interestingly, treatment with this steroid attenuated the mRNA levels for both anabolic and catabolic molecules.

Dexamethasone inhibits inflammation and cartilage damage in a new model of post‐traumatic osteoarthritis

Corticosteroids are used in musculoskeletal diseases, and offer patient relief. Injections of corticosteroids are recommended for management of osteoarthritis (OA). Current data have shown the role of corticosteroids in ameliorating pain. We hypothesized that repeated intra-articular injections of high dose dexamethasone would protect the cartilage from damage in a post-traumatic model of OA. Eighteen female New Zealand White rabbits were used. Twelve underwent surgery to induce OA; six of them received intra-articular injections of dexamethasone every 3 days for 3 weeks. The other six rabbits served as operated controls. Six additional rabbits served as non-operated controls. All animals were euthanized 3 weeks post-surgery. Knees were assessed grossly. Cartilage, synovium, and fat pad were assessed histologically. Synovium and fat pad were analyzed with qPCR and Western blots. Surgical controls had cartilage damage which was supressed with dexamethasone. Dexamethasone significantly decreased synovial expression of interleukin-1β and collagen I, and a trend to decrease synovial matrix metalloproteinase3 expression. There were also significantly lower levels of interleukin-1β protein with dexamethasone treatment. Dexamethasone significantly decreased fat pad expression of matrix metalloproteinase13, basic fibroblast growth factor, and interleukin8, and a trend to decrease matrix metalloproteinase3 and transforming growth factorβ expression. Dexamethasone decreased joint inflammation and joint tissue degradation and was chondroprotective in this unique model of PTOA.

Subchondral chitosan/blood implant-guided bone plate resorption and woven bone repair is coupled to hyaline cartilage regeneration from microdrill holes in aged rabbit knees

Little is known of how to routinely elicit hyaline cartilage repair tissue in middle-aged patients. We tested the hypothesis that in skeletally aged rabbit knees, microdrill holes can be stimulated to remodel the bone plate and induce a more integrated, voluminous and hyaline cartilage repair tissue when treated by subchondral chitosan/blood implants. New Zealand White rabbits (13 or 32 months old, N = 7) received two 1.5 mm diameter, 2 mm depth drill holes in each knee, either left to bleed as surgical controls or press-fit with a 10 kDa (distal hole: 10K) or 40 kDa (proximal hole: 40K) chitosan/blood implant with fluorescent chitosan tracer. Post-operative knee effusion was documented. Repair tissues at day 0 (N = 1) and day 70 post-surgery (N = 6) were analyzed by micro-computed tomography, and by histological scoring and histomorphometry (SafO, Col-2, and Col-1) at day 70. All chitosan implants were completely cleared after 70 days, without increasing transient post-operative knee effusion compared to controls. Proximal control holes had worse osteochondral repair than distal holes. Both implant formulations induced bone remodeling and improved lateral integration of the bone plate at the hole edge. The 40K implant inhibited further bone repair inside 50% of the proximal holes, while the 10K implant specifically induced a "wound bloom" reaction, characterized by decreased bone plate density in a limited zone beyond the initial hole edge, and increased woven bone (WB) plate repair inside the initial hole (P = 0.016), which was accompanied by a more voluminous and hyaline cartilage repair (P < 0.05 vs control defects). In a challenging aged rabbit model, bone marrow-derived hyaline cartilage repair can be promoted by treating acute drill holes with a biodegradable subchondral implant that elicits bone plate resorption followed by anabolic WB repair within a 70-day repair period.

Disconnection of a basal ganglia circuit in juvenile songbirds attenuates the spectral differentiation of song syllables

Similar to language acquisition by human infants, juvenile male zebra finches (Taeniopygia guttata) imitate an adult (tutor) song by transitioning from repetitive production of one or two undifferentiated protosyllables to the sequential production of a larger and spectrally heterogeneous set of syllables. The primary motor region that controls learned song is driven by a confluence of input from two premotor pathways: a posterior pathway that encodes the adult song syllables and an anterior pathway that includes a basal ganglia (BG)-thalamo-cortical circuit. Similar to mammalian motor-learning systems, the songbird BG circuit is thought to be necessary for shaping juvenile vocal behaviour (undifferentiated protosyllables) toward specific targets (the tutor's song syllables). Here, we tested the hypothesis that anterior pathway activity contributes to the process of protosyllable differentiation. Bilateral ablation of lateral magnocellular nucleus of the anterior nidopallium (LMAN) was used to disconnect BG circuitry at ages before protosyllable production and differentiation. Comparison to surgical controls revealed that protosyllables fail to differentiate in birds that received juvenile LMAN ablation--the adult songs of birds with >80% bilateral LMAN ablation consisted of only one or two syllables produced with the repetitive form and spectral structure that characterizes undifferentiated protosyllables in normal juveniles. Our findings support a role for BG circuitry in shaping juvenile vocal behaviour toward the acoustic structure of the tutor song and suggest that posterior pathway function remains in an immature "default" state when developmental interaction with the anterior pathway is reduced or eliminated.

Assessment of epidural versus intradiscal biocompatibility of PEEK implant debris: an in vivo rabbit model

To understand the relative histopathological effects of PEEK particulate debris when applied within the epidural versus the intervertebral disc space. We hypothesized that due to the avascular nature of the intervertebral disc acting as a barrier to immune cells, the intradiscal response would be less than the epidural response. The inflammatory effects of clinically relevant doses (3 mg/5-kg rabbit) and sizes (1.15 µm diameter) of PEEK implant debris were assed when placed dry on epidural and intradiscal tissues in an in vivo rabbit model. The size of the particulate was based on wear particulate analysis of wear debris generated from simulator wear testing of PEEK spinal disc arthroplasty devices. Local and systemic gross histology was evaluated at the 3- and 6-month time points. Quantitative immunohistochemistry of local tissues was used to quantify the common inflammatory mediators TNF-α, IL-1β, and IL-6. Both treatments did not alter the normal appearance of the dura mater and vascular structures; however, limited epidural fibrosis was observed. Epidural challenge of PEEK particles resulted in a significant (30 %) increase (p < 0.007) in TNF-α and IL-1β at both 3 and 6 months compared to that of controls, and IL-6 at 6 months (p < 0.0001). Intradiscal challenge of PEEK particles resulted in a significant increase in IL-1β, IL-6 and TNF-α at 6-months post-challenge (p ≤ 0.03). However, overall there were only moderate increases in the relative amount of these cytokines when compared with surgical controls (10-20 %). In contrast, epidural challenge resulted in a 50-100 % increase. The results of this study are similar to past investigations of PEEK, whose results have not been shown to elicit an aggressive immune response. The degree to which these results will translate to the clinical environment remains to be established, but the pattern of subtle elevations in inflammatory cytokines indicated both a mild persistence of responses to PEEK debris, and that intradiscal implant debris will likely result in less inflammation than epidural implant debris.

CD34 affinity pheresis attenuates a surge among circulating progenitor cells following vascular injury

Intimal hyperplasia (restenosis) is an exaggerated healing response leading to failure of half of vascular interventions. Increasing evidence suggests that circulating progenitor cells contribute to intimal pathology, and clinical studies have demonstrated a correlation between progenitor cells and the incidence of restenosis after cardiovascular interventions. The aims of this study were to characterize the temporal response of CD34+ progenitors following vascular injury in an ovine model and to evaluate an affinity pheresis approach to attenuate this response. An ovine model underwent either operative vascular injury or a nonvascular surgery (n = 3 per group). Blood was examined perioperatively over 2 weeks by flow cytometry. Next, an affinity pheresis approach to mediate systemic depletion of CD34 progenitors was designed. Custom agarose pheresis matrix with antibody affinity toward CD34 or an isotype control was evaluated in vitro. Next, following vascular injury, sheep underwent perioperative whole blood volume pheresis toward either the progenitor cell marker CD34 (n = 3) or an isotype control (n = 4) for 14 days. Animals were monitored by physical exam as well as complete blood counts. Cells recovered by pheresis were eluted and examined by flow cytometry. Flow cytometry revealed a focal surge of circulating CD34 cells after vascular injury but not among surgical controls (P = .05). Toward the goal of an approach to attenuate the surge of CD34 progenitors, an evaluation of high-flow affinity matrix revealed efficacy in removal of progenitors from ovine blood in vitro. Next, a separate group of animals undergoing affinity pheresis after vascular injury was evaluated to mediate systemic depletion of CD34+ cells. Again, a surge of CD34+ cells was observed among isotype pheresis animals following vascular intervention but was attenuated over 20-fold by a CD34 pheresis approach (P = .029). Furthermore, an average of 77 million CD34-positive cells were eluted from the CD34 pheresis matrix. Despite multiple sessions of pheresis, complete blood counts remained essentially unchanged over 2 weeks. Despite evidence suggesting a role for CD34+ circulating progenitor cells in restenotic pathology, the temporal pattern of CD34 progenitors after vascular injury has not been previously defined. We have demonstrated a surge among circulating CD34+ cells that appears confined to procedures involving vascular injury and that this event seems to occur early after vascular injury. We further conclude that CD34 affinity pheresis attenuates the surge. This approach for direct depletion of progenitors may have important implications for the study of progenitors in vascular restenosis.

Improvement in hepatic insulin sensitivity after Roux-en-Y gastric bypass in a rat model of obesity is partially mediated via hypothalamic insulin action

Roux-en-Y gastric bypass (RYGB) surgery, an effective treatment for morbid obesity, commonly leads to near complete resolution of type 2 diabetes. The underlying mechanisms, however, remain unclear and factors other than weight loss alone may be involved. To determine whether increased hypothalamic insulin sensitivity after RYGB drives the rapid improvement in glucose metabolism, high-fat-fed rats received either an insulin receptor (IR) antisense vector or a control lentiviral vector that was microinjected into the ventromedial hypothalamus (VMH). Six weeks later, rats underwent RYGB or control gastrointestinal surgery. Four weeks after surgery, weight loss was comparable in RYGB and surgical controls. Nevertheless, only RYGB rats that received the control vector demonstrated both improved hepatic and peripheral insulin sensitivity. Insulin suppressed hepatic glucose production (HGP) by 50% (p < 0.05) with RYGB, whereas the effect of insulin on HGP was completely absent in VMH IR knockdown (IRkd) rats. By contrast, both RYGB groups displayed an identical twofold increase in insulin-stimulated peripheral glucose uptake. The animals that underwent control gastrointestinal surgery failed to show any improvement in either hepatic or peripheral insulin sensitivity; VMH IRkd did not influence the magnitude of insulin resistance. Our findings demonstrate that RYGB surgery in high-fat-fed obese rats enhances hepatic and peripheral insulin sensitivity independently of weight loss. The improved hepatic, but not the peripheral, response to insulin is mediated centrally at the level of the VMH. These data provide direct evidence that the metabolic benefits of RYGB surgery are not simply a consequence of weight loss but likely in part involve the central nervous system.

Overall survival advantage with partial nephrectomy: A bias of observational data?

Partial nephrectomy (PN) and radical nephrectomy (RN) are standard treatments for a small renal mass. Retrospective studies suggest an overall survival (OS) advantage, however a randomized phase 3 trial suggests otherwise. The effects of both surgical modalities on OS were evaluated compared with controls. A matched cohort study was performed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset. Individuals treated with PN or RN for localized renal cell carcinoma (RCC) measuring ≤4 cm were compared with 2 control groups (non-muscle-invasive bladder cancer (BCC) and noncancer controls (NCC). Using a greedy algorithm, RCC groups were matched with controls by demographics and comorbidities. OS for surgical groups and controls were compared. The cause of death was evaluated for cancer groups when differences in OS were noted. Patients undergoing PN and RN were matched with controls. All cancer groups had >95% 10-year cancer-specific survival (CSS). Median OS was similar between RN (9.05 years) and BCC (8.67 years; P = .067) and NCC (8.77 years; P = .49). Median OS was improved for PN (10.45 years) compared with BCC (8.75 years; P<.001) and NCC controls (8.76 years; P<.001). A multivariate Cox hazards model demonstrated that PN improved OS compared with NCC (hazard ratio, 1.257; P<.001) and BCC (hazard ratio, 1.364; P<.001). RN patients had similar OS compared with controls, suggesting that this treatment modality does not compromise survival. Patients undergoing PN had improved OS compared with controls, suggesting possible selection bias. The apparent survival advantage conferred by PN in SEER-Medicare case series is likely the result of selection bias involving unmeasured confounders.

What Can We Learn From MOTHER?

In 1953, DeBakey and Cooley1 successfully resected a large aneurysm of the descending thoracic aorta and replaced it with a homograft by using a clamp-and-sew approach. The techniques used in contemporary open surgical repair by synthetic graft replacement are essentially unchanged since the early days of descending thoracic aortic repair. In the 1980s, Volodos et al2 and Parodi and colleagues3 pioneered the use of endovascular aortic stent grafts to repair thoracic and abdominal aortic aneurysms. Soon thereafter, Dake et al4 were instrumental in popularizing their use to repair descending thoracic aortic aneurysms. Pivotal trials (with stringent patient selection) were performed to establish the noninferiority of this newly emerging technology compared with standard open repair of aortic aneurysm.5,6 Concurrent open surgical controls were not used in any of the clinical trials targeted for US Food and Drug Administration approval. Article see p 24 The primary goal of both open and endovascular aortic aneurysm repair is to prevent death as a result of aortic rupture. Although early outcomes clearly favor endovascular therapy, the superiority of one technique over another has not yet been firmly established for thoracic endovascular aortic repair (TEVR), because long-term data are still lacking. Since the Food and Drug Administration approved TEVR in 2005, the use of this approach to treat thoracic aortic pathology has grown. This growth includes off-label applications of TEVR, such as treating acute and chronic aortic dissection. It is estimated that currently, off-label applications constitute well over half of all TEVRs.7,8 Although the use of TEVR as a definitive treatment for either acute9 or chronic10 aortic dissection remains controversial, its use in emergent, complicated cases of acute DeBakey type III aortic dissection is generally considered acceptable and potentially lifesaving; in fact, in many …

Surgical lesions of the small colon and post operative survival in aUKhospital population

There is limited information about risk factors and survival associated with disorders of the small colon requiring surgical management. 1) To document the types of surgical lesion in horses where pathology of the small (descending) colon was the primary cause of abdominal pain, 2) to describe the short- and long-term survival of these cases and identify factors associated with survival and 3) to identify preoperative variables associated with localisation of a lesion to the small colon. Clinical data and long-term follow-up were obtained for horses that underwent exploratory laparotomy over a 10-year period. Descriptive data were generated for short- and long-term survival and survival analysis performed to identify factors associated with reduced survival. Univariable and multivariable relationships were explored using a Cox proportional hazards model. Preoperative factors associated with increased likelihood of a small colon lesion were explored, using controls randomly selected from horses undergoing exploratory laparotomy for treatment of colic unrelated to the small colon. The study population included 84 horses. Of horses with small colon lesions recovered from anaesthesia, the percentage that survived until discharge, one year and 2 years following surgery, was 91.0, 81.0 and 73.5%, respectively. Median survival time for horses in which a resection had been performed was 1029 vs. 3072 days in the nonresection group. Small colon cases were more likely to have shown a longer duration of colic signs prior to admission (P<0.001) and to develop post operative diarrhoea (P = 0.001) when compared with surgical controls. Lesions of the small colon carry a good prognosis for survival following surgery. Resection and anastomosis was the only factor associated with reduced long-term survival. This study provides information about lesion types and post operative survival that may be used to assist informed decision-making when managing these cases.

Do Breast Implants Adversely Affect Prognosis among Those Subsequently Diagnosed with Breast Cancer? Findings from an Extended Follow-Up of a Canadian Cohort

Cosmetic breast implants may impair the ability to detect breast cancers. The aims of this study were to examine whether implants and implant characteristics are associated with more advanced breast tumors at diagnosis and poorer survival. Study population includes all invasive breast cancer cases diagnosed during follow-up of the large Canadian Breast Implant Cohort. A total of 409 women with cosmetic breast implants and 444 women with other cosmetic surgery were diagnosed with breast cancer. These women were compared for stage at diagnosis using multinomial logistic regression models. Cox proportional hazards regression models were used for breast cancer-specific mortality analyses. Comparisons were also conducted according to implant characteristics. Compared with women with other cosmetic surgery, those with cosmetic breast implants had at later stage breast cancer diagnosis (OR of having stage III/IV vs. stage I at diagnosis: 3.04, 95% confidence interval (CI): 1.81-5.10; P < 0.001). A nonstatistically significant increase in breast cancer-specific mortality rate for women with breast implants relative to surgical controls was observed (HR = 1.32, 95% CI: 0.94-1.83, P = 0.11). No statistically significant differences in stage and breast cancer mortality were observed according to implant characteristics. At diagnosis, breast cancers tended to be at more advanced stages among women with cosmetic breast implants. Breast cancer-specific survival was lower in these women although the reduction did not reach statistical significance. Further investigations of the effect of breast implants on breast cancer prognosis are warranted.

Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients

BackgroundVarious human cardiovascular pathophysiological conditions associate aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as promising biomarkers. In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. This study was designed to determine the role of myocardial and plasmatic miR-21 in the maladaptive remodeling of the extracellular matrix induced by pressure overload in aortic stenosis (AS) patients and the clinical value of miR-21 as a biomarker for pathological myocardial fibrosis. MethodsIn left ventricular biopsies from 75 AS patients and 32 surgical controls, we quantified the myocardial transcript levels of miR-21, miR-21-targets and ECM- and TGF-β-signaling-related elements. miR-21 plasma levels were determined in 25 healthy volunteers and in AS patients. In situ hybridization of miR-21 was performed in myocardial sections. ResultsThe myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with the controls and correlated directly with the echocardiographic mean transvalvular gradients. miR-21 overexpression was confined to interstitial cells and absent in cardiomyocytes. Using bootstrap validated multiple linear regression, the variance in myocardial collagen expression was predicted by myocardial miR-21 (70% of collagen variance) or plasma miR-21 (52% of collagen variance), together with the miR-21 targets RECK and PDCD4, and effectors of TGF-ß signaling. ConclusionsOur results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis.

Bariatric Surgery is Associated with a Reduced Risk of Mortality in Morbidly Obese Patients with a History of Major Cardiovascular Events

Although the safety of bariatric surgery in patients with established cardiovascular disease has been demonstrated, little is known about the mid- to long-term survival of these patients after surgery. We conducted a retrospective cohort study of bariatric surgical patients (n = 349) compared with morbidly obese surgical controls (n = 903). Data were obtained on all patients 40 to 79 years of age, from 1996 to 2008, with a diagnosis code of morbid obesity, a primary surgical procedure of interest, and a cardiovascular event history. Data sources were the statewide South Carolina UB92 inpatient hospitalization database and death records. The primary outcome was all-cause mortality. A total of 349 bariatric and 903 control patients with cardiovascular event histories were identified. Among bariatric patients, 19 deaths occurred in 986 person-years of follow-up versus 150 deaths among controls in 3138 person-years of follow-up. Unadjusted all-cause mortality was estimated at 7 ± 2 per cent at 5 years in bariatric patients compared with 19 ± 2 per cent (P < 0.001) in controls. Adjusting for age, comorbidities, and event history, the relative risk of mortality was reduced by 40 per cent in bariatric patients compared with controls [hazard ratios (95% confidence interval): 0.60 (0.36, 0.99)]. In patients with a history of cardiovascular events, bariatric surgery is associated with a significantly decreased risk of all-cause mortality.

Impact of county-level surgical specialist density on breast (BrCa) and lung cancer (LuCa) mortality.

6064 Background: Variations in distribution of the surgical workforce may result in differential access to cancer screening and treatment. Our aim was to explore the relationship between county-level surgical specialist density and BrCa and LuCa mortality. Methods: Using data from Area Resource File, US Census and National Cancer Institute, regression models that controlled for cancer incidence, county demographics and socioeconomic factors were constructed to examine the association among a) general surgeon (GS) and radiation oncologist (RO) density with BrCa mortality and b) thoracic surgeon (ThS) and RO density with LuCa mortality. Plastic (PS) and transplant surgeons (TrS) were used as surgical controls as they were not expected to correlate significantly with BrCa or LuCa mortality. Results: A total of 1,557 and 2,044 US counties were analyzed for BrCa and LuCa, respectively: mean incidences were 119 and 75 and death rates were 25 and 59 per 100,000 people, respectively, for BrCa and LuCa. Mean specialist densities were 7.72 (GS), 0.80 (RO), and 0.97 (PS) [for BrCa counties] and 0.55 (ThS), 0.55 (RO), and 0.01 (TrS) [for LuCa counties] per 100,000. When compared to counties with no surgical specialist, those with at least one GS and RO for BrCa and at least one ThS and RO for LuCa were associated with decreased mortality (Table). Increasing the density of GS and RO beyond 9 and 1 per 100,000 did not result in significant reductions in BrCa mortality. Likewise, increasing the density of ThS and RO to above 1 each per 100,000 failed to yield further improvements in LuCa mortality. Counties with more elderly residents also correlated with worse BrCa and LuCa outcomes. Conclusions: The presence of specific surgical specialists is associated with lower BrCa and LuCa mortality. There appears to be a threshold at which point further increase in their density do not contribute to continued improvements in outcomes. Distributing the surgical workforce across all counties will offer population-based improvements in BrCa and LuCa mortality. [Table: see text]

Calcimimetics Versus Parathyroidectomy for Treatment of Primary Hyperparathyroidism

This study aims to determine the efficacy of calcimimetics in improving bone mineral density (BMD) in patients with primary hyperparathyroidism (pHPT) and compare those results to patients undergoing parathyroidectomy. Parathyroidectomy has been shown to improve BMD in pHPT, but calcimimetics have recently been advocated as a medical alternative to parathyroidectomy for pHPT. We identified 17 patients that were treated with calcimimetics for pHPT. Seventeen patients with pHPT who underwent parathyroidectomy served as surgical controls. Serum calcium level, parathyroid hormone (PTH) level, and femur and spine BMD T scores were compared before and 1 year after therapy. Both groups were demographically matched. Calcium levels normalized in 70.6% of medically versus 100% of surgically treated patients (P = 0.026). PTH levels normalized in 35% of patients treated with calcimimetics versus 76% of surgical patients (P = 0.036). Femur BMD improved in 18.8% of medically treated patients versus 58.8% of surgical patients (P = 0.032). Spine BMD improved in 70.6% of medically treated patients versus 82.4% of surgical patients (P = 0.69). Further analysis demonstrated that regardless of treatment, normalization of PTH was associated with significant improvement in femur (P = 0.03) and spine BMD (P < 0.001). Normalization of calcium without normalization of PTH did not impact BMD. Parathyroidectomy results in greater normalization of serum calcium and PTH levels and significantly improves cortical BMD compared to calcimimetics. Regardless of treatment, normalization of PTH is associated with significant improvement in spine and femur BMD, suggesting that the superior effects of surgery may be mediated by better control of PTH.

Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratios

BackgroundNecrotising enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. Immaturity of gastrointestinal immune regulation may predispose preterm infants to NEC as FOXP3 T regulatory cells (Treg) are...

Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case-control study

BackgroundNormal bronchial tissue expression of GRPR, which encodes the gastrin-releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females. We sought to define the contribution of GRPR expression in bronchial epithelia to lung cancer risk in a larger case-control study where adjustments could be made for tobacco exposure and sex.MethodsWe evaluated GRPR mRNA levels in histologically normal bronchial epithelial cells from 224 lung cancer patients and 107 surgical cancer-free controls. Associations with lung cancer were tested using logistic regression models.ResultsBronchial GRPR expression was significantly associated with lung cancer (OR = 4.76; 95% CI = 2.32-9.77) in a multivariable logistic regression (MLR) model adjusted for age, sex, smoking status and pulmonary function. MLR analysis stratified by smoking status indicated that ORs were higher in never and former smokers (OR = 7.74; 95% CI = 2.96-20.25) compared to active smokers (OR = 1.69; 95% CI = 0.46-6.33). GRPR expression did not differ by subject sex, and lung cancer risk associated with GRPR expression was not modified by sex.ConclusionsGRPR expression in non-cancerous bronchial epithelium was significantly associated with the presence of lung cancer in never and former smokers. The association in never and former smokers was found in males and females. Association with lung cancer did not differ by sex in any smoking group.

Estradiol Treatment Prevents Injury Induced Enhancement in Spinal Cord Dynorphin Expression

Administration of the ovarian steroid estradiol in male and female animals has been shown to have neuromodulatory and neuroprotective effects in a variety of experimental models. In the present study, spinal tissues from dermatomes just above (T5–T7, at level) a severe chronic spinal cord injury (SCI) at T8 were analyzed for expression levels of prodynorphin (PRDN) and phospho-(serine 369) κ-opioid receptor (KOR-P) in 17 β estradiol (EB)- and placebo-treated adult male rats. Dynorphin was targeted since (1) it has previously been shown to be elevated post-SCI, (2) intrathecal injection of dynorphin produces several of the same adverse effects seen with a SCI, and (3) its increased expression is known to occur in a variety of different experimental models of central neuropathic pain. A significant elevation of extracellular levels of both PRDN and KOR-P in the placebo-treated SCI group relative to uninjured surgical sham controls was found in spinal tissues above the injury level, indicating increased dynorphin levels. Importantly, the EB-treated SCI group did not show elevations of PRDN levels at 6 weeks post-injury. Immunohistochemical analysis of at level tissues revealed that EB treatment significantly prevented a post-SCI increase in expression of PRDN puncta co-labeling synapsin I, a nerve terminal marker. The dynorphin-containing terminals co-labeled vesicular glutamate receptor-2 (a marker of glutamatergic terminals), a finding consistent with a non-opioid basis for the adverse effects of dynorphin. These results support a beneficial role for EB treatment post-SCI through a reduction in excessive spinal cord levels of dynorphin. Studies manipulating the timing of the EB treatment post-injury along with specific functional assessments will address whether the beneficial effects are due to EB’s potential neuromodulatory or neuroprotective action.