eScholarship@UMMS

Laparoscopic repair of inguinal hernias is gaining acceptance in the repertoire of the general surgeon. However, nerve entrapment sequelae have been reported and appear to be higher with the laparoscopic approach. Contributing factors include pelvic variations in nerve pathways and the use of staples. We examined the pelvic relations of the lateral femoral cutaneous nerve (LFCN) to the anterior superior iliac spine (ASIS) and the iliopubic tract (IPT) because of the high morbidity of entrapment of this nerve, despite its low incidence. The LFCN, ASIS, and IPT were identified and their relationships measured in 48 male and 24 female cadavers ranging in age from 61 to 96 yr. The LFCN was located 1.7 (+/- 1.2) cm medial to the ASIS along the IPT and 1.4 (+/- 0.7) cm posterior (deep) to the IPT at this point, with no significant sex differences. The intrapelvic pathway of the LFCN, including its branches, varied widely so that in 18% of these specimens the LFCN was in either the vertical plane of the ASIS (13%) or in the plane of the IPT (5%). In 11% this nerve was within 1 cm of the ASIS. These data indicate that exclusive use of the ASIS as a guide for staple placement may result in entrapment of this nerve or its branches.

Laparoscopic approaches for abdominal surgery are being used with increasing frequency. Their advantages are sometimes negated by the disturbing incidence of postoperative sequelae. In the case of inguinal hernia repair, these are often the result of failing to understand that the anatomy of the anterior approach to the abdominal wall cannot necessarily be directly applied to laparoscopy. The inguinal ligament, easily identified in an anterior approach, is only seen laparoscopically after removal of the iliopubic tract, a key structure which lies in the plane of the original defect of most groin hernias. Thus, an understanding of the incompletely trilaminar anterior abdominal wall, including the iliopubic tract, is the foundation for effective inguinal hernia repair using any approach (anterior or posterior) or technique (sutures, mesh or staples). Laparoscopic inguinal hernia repair has produced an increase in the frequency of debilitating neuropathies, most notably of the lateral femoral cutaneous nerve (LFCN). This is directly related to the variable intrapelvic course of this nerve or its branches. In more than 13% of the 114 pelves we examined, the LFCN was within 0.5 cm of the iliopubic tract or in the vertical plane of the anterior superior iliac spine, key lateral landmarks and anchoring sites for mesh in laparoscopic hernia repairs. Medial landmarks also have variable features. These data indicate that the identity of anatomical landmarks and the variability of other structures will continue to be important in the successful development of new laparoscopic techniques.

The obturator artery and vein are usually described as branches or tributaries of the internal iliac vessels although variations with connections to the external iliac or inferior epigastric vessels have been reported. Because these anomalous vessels are at risk in groin or pelvic surgeries that require dissection or suturing along the pelvic rim, we measured the frequency of these variations in 105 pelvic walls (45 in the United States and 60 in China). Our data show that 70-82% of pelvic halves and 83-90% of whole pelves had an artery, vein, or both in the variant position. Arteries were most often found in the normal position only but normal and anomalous veins were most frequently found together. These data show that it is far more common to find a vessel coursing over the pelvic rim at this site than not and have implications for both pelvic surgeons and anatomists.

We report a rare case of covered cloacal exstrophy variant with a hemiphallus trapped within partially closed bladder halves. The persistence of the cloacal membrane until at least 18 weeks' gestation, confirmed by antenatal ultrasound scanning, is discordant with existing theories of embryogenesis of cloacal exstrophy. The clinical presentation highlights the need for careful assessment, before and during surgery, to obtain a complete understanding of the anatomic defect before gender assignment and appropriate reconstructive efforts. A multispecialty approach and antenatal counseling are important, especially when only one fetus of twins has major birth defects.

In mice, pregnancy has been shown to have a beneficial effect on the endogenous repair of focal lysolecithin-induced CNS demyelinative lesions, enhancing the genesis of new oligodendrocytes and the degree of remyelination. To identify local cells undergoing mitosis in response to such lesions, we examined the time course of phospho-histone H3 (PH3) and myelin basic protein (MBP) expression by immunohistochemistry. After lysolecithin injection into the corpus callosum of virgin female mice, the number of dividing cells peaked about 48 h after injection and declined gradually to baseline by day 7; in pregnant mice, this initial peak was unchanged, but a new delayed peak on day 4 was induced. Colocalization data using PH3 and NG2 proteoglycan, or bromodeoxyuridine (BrdU) and oligodendrocyte transcription factor 1 (Olig1), suggested that about 75% of the proliferating cells on day 2, and about 40% of the cells on day 4, were likely of oligodendrocyte lineage; these differential percentages were of the same magnitude in both virgin and pregnant animals. Notably, the heightened proliferative response to focal lysolecithin injection during pregnancy was specific to gestational stage (early, but not late) and to lesion location (in the corpus callosum of the periventricular forebrain, but not in the caudal cerebellar peduncle of the hindbrain).

The Graduate School of Nursing Papers documents the establishment of the Graduate School of Nursing at the University of Massachusetts Medical School, and chronicles its early history and development.

This resource is a comprehensive tutorial for intravenous fluid resuscitation and blood product replacement during the management of postpartum hemorrhage. This module was prepared for use in residencies with significant obstetrical training but is appropriate for use by any individual seeking detailed information on fluid and blood product resuscitation in the management of postpartum hemorrhage. It can be used in conjunction with postpartum hemorrhage simulation, in support of didactic sessions and as a stand-alone discussion or review of the subject matter. The presentation contains a narrated PowerPoint slide set with embedded summary tables. There is a transcription of all audio narration so that the resource is usable for the hearing impaired. This module was developed as part of a comprehensive blended learning curriculum for teaching the management of postpartum hemorrhage. The full curriculum included 7 on-line modules followed by face-to-face teaching and learning with task trainers and a multi-disciplinary simulation case.

This resource is an audiovisual tutorial for pharmacologic management of postpartum hemorrhage. This module was prepared for use in residencies with significant obstetrical training but is appropriate for use by any individual seeking detailed information on pharmacologic management of postpartum hemorrhage. It can be used in conjunction with postpartum hemorrhage simulation, in support of didactic sessions, and as a stand-alone discussion or review of the subject matter. The presentation contains a narrated PowerPoint slide set with embedded summary tables. There is a transcription of all audio narration so that the resource is usable for the hearing impaired. This module was developed as part of a comprehensive blended learning curriculum for teaching the management of postpartum hemorrhage. The full curriculum included 7 on line modules followed by face-to-face teaching and learning with task trainers and a multi-disciplinary simulation case.

This resource is a comprehensive tutorial for non pharmacologic vaginal management of postpartum hemorrhage. Management methods addressed include but are not limited to: 1.) Uterine exploration and evacuation including dilation and curettage and 2.) Uterine tamponade techniques including uterine packing and use of commercial products. This module was prepared for use in residencies with significant obstetrical training but is appropriate for use by any individual seeking detailed information on initial conservative management of postpartum hemorrhage. It can be used in conjunction with postpartum hemorrhage simulation, in support of didactic sessions and as a stand-alone discussion or review of the subject matter. All procedures are presented in overview with attached step-by-step instructional guides and videos. The presentation contains a narrated PowerPoint slide set with embedded videos. There is a transcription of all audio narration so that the resource is usable for the hearing impaired.

We previously reported that Mycobacterium tuberculosis triggers macrophage necrosis in vitro at a threshold intracellular load of ~25 bacilli. This suggests a model for tuberculosis where bacilli invading lung macrophages at low multiplicity of infection proliferate to burst size and spread to naïve phagocytes for repeated cycles of replication and cytolysis. The current study evaluated that model in vivo, an environment significantly more complex than in vitro culture. In the lungs of mice infected with M. tuberculosis by aerosol we observed three distinct mononuclear leukocyte populations (CD11b(-) CD11c(+/hi), CD11b(+/lo) CD11c(lo/-), CD11b(+/hi) CD11c(+/hi)) and neutrophils hosting bacilli. Four weeks after aerosol challenge, CD11b(+/hi) CD11c(+/hi) mononuclear cells and neutrophils were the predominant hosts for M. tuberculosis while CD11b(+/lo) CD11c(lo/-) cells assumed that role by ten weeks. Alveolar macrophages (CD11b(-) CD11c(+/hi)) were a minority infected cell type at both time points. The burst size model predicts that individual lung phagocytes would harbor a range of bacillary loads with most containing few bacilli, a smaller proportion containing many bacilli, and few or none exceeding a burst size load. Bacterial load per cell was enumerated in lung monocytic cells and neutrophils at time points after aerosol challenge of wild type and interferon-γ null mice. The resulting data fulfilled those predictions, suggesting a median in vivo burst size in the range of 20 to 40 bacilli for monocytic cells. Most heavily burdened monocytic cells were nonviable, with morphological features similar to those observed after high multiplicity challenge in vitro: nuclear condensation without fragmentation and disintegration of cell membranes without apoptotic vesicle formation. Neutrophils had a narrow range and lower peak bacillary burden than monocytic cells and some exhibited cell death with release of extracellular neutrophil traps. Our studies suggest that burst size cytolysis is a major cause of infection-induced mononuclear cell death in tuberculosis.

Background: In patients with coronary artery disease (CAD), epicardial adipose tissue (EAT) has been shown to express increased levels of inflammatory cytokines (IL-1β, IL-6, MCP-1, TNFα) and decreased levels of anti-inflammatory and cardioprotective adipokines. However, it is not known whether or not inflammation in EAT is a primary cause or a secondary response to atherosclerosis. In order to better understand this pathophysiology, we tested the hypothesis that expression of certain genes in EAT would correlate with the degree of coronary atherosclerosis.

Purpose: The purpose of this study was to determine whether there is a difference in gene expression in epicardial fat of patients with and without coronary artery disease and if there is a difference, whether these differentially expressed genes participate in the inflammatory pathways.

Methods: EAT and paired subcutaneous adipose tissue (SAT) samples collected from cardiac surgery patients with and without coronary disease were fixed for microscopy and frozen for RNA extraction. RNA was hybridized to Affymetrix Human Gene 1.0 ST chips. We used an unbiased approach to identify genes highly and differentially expressed in EAT vs. SAT (FC>3.0). The probe intensities for these resultant genes were then correlated with the severity of atherosclerosis in each patient as determined by the Gensini score.

Results: 35 genes were differentially expressed in EAT at >3.0 fold change (p<0.05). Of these, 14 genes were significantly correlated with the degree of atherosclerosis, quantified by Gensini score. Integrin αvβ8 (ITGB8) and transglutaminase 2 (TGM2) were both more highly expressed in EAT than in SAT (p<0.009) for all patients. Expression of ITGB8 had the strongest positive correlation (r=0.94, p<0.01), while TGM2 had the strongest negative correlation (r=-0.80, p<0.01) (Fig. 1). Importantly, expression of neither ITGB8 nor TG2 in SAT correlated with the extent of atherosclerosis.

Conclusions: Using an unbiased whole genome approach, we identified ITGB8 and TG2 as genes whose expression is correlated with CAD severity. ITGB8 has been previously shown to be expressed by fibroblasts and functions to activate TGFβ. TGFβ signaling has also been correlated with advanced atherosclerosis. We speculate that EAT expression of ITGB8 may have pro-inflammatory effects, possibly by activating TGFβ, and stimulating recruitment of dendritic cells or T cells to secondary lymphoid organs in EAT. Whether or not this is the case is a goal of future studies.

Background: Throughout the world, baby boomers reaching their sixth, seventh, and eighth decade of life are requiring a significant number of joint replacements—hips and knees. Due to the increasing number of joint replacements, it is important to find a multi-modal approach (MMA) to control pain, reduce the amount of opioid consumption, and improve patient satisfaction.

Purpose: The purpose of this study was to evaluate the intraoperative, postoperative, and total opioid consumption of patients undergoing total hip and knee replacements in an effort to develop a multi-modal approach to decrease opioid consumption, minimize adverse effects secondary to narcotic administration, and to achieve better pain control. This MMA was achieved by administering oxycodone, gabapentin, celecoxib, and acetaminophen starting before surgical incision.

Methods: The study sample consisted of 192 patients undergoing total hip and knee replacements over a 10-month period between June 2012 and March 2013 at UMASS Memorial performed by five orthopedic surgeons. The main objective was to record intraoperative, postoperative, total opioid consumption, and patient satisfaction amongst these patients. Furthermore, the patients were subdivided based on the type of procedure (hip vs knee), type of anesthetic (general vs spinal), and the presence or absence of an indwelling catheter to deliver anesthetic (catheter vs no catheter).

Results: The data showed a large variability among the surgeons in regards to the amount of opioid used intraoperatively, postoperatively and total opioid consumption. In terms of type of anesthetic, the patients undergoing spinal anesthesia used statistically significantly less opioids intraoperatively but not postoperatively, compared to general anesthesia. As for catheter use with general and spinal anesthesia, surprisingly, there was no significant difference in opioid consumption compared to the non-catheter counterpart. Furthermore, there seems to be no correlation between body mass index (BMI) and intraoperative or postoperative opioid use. Patient satisfaction was another variable that showed no correlation with opioid use intraoperatively or postoperatively. In terms of age, the data suggests that older patients use less opioids postoperatively in both hip and knee replacements.

Conclusions: Our results quantitatively show spinal anesthesia to be far superior than general anesthesia in both joint replacements. Spinal anesthesia provides better pain control intraoperatively which allows one to use less opioids, thereby minimizing the adverse side effects of narcotic administration which include respiratory depression, urinary retention, nausea and post-operative ileus to name just a few. One surgeon’s patients required significantly less opioids intraoperatively compared to the rest of the surgeons. Further studies might warrant examining this surgeon’s technique or the demographics of his patient population to determine how better pain control and less opioid consumption could be achieved across all joints with all participating surgeons.

A brief overview of UMass Medical School's recent application of altmetrics in one collection in the medical school's institutional repository, eScholarship@UMMS.

Throughout the animal kingdom, steroid hormones have been implicated in the defense against microbial infection, but how these systemic signals control immunity is unclear. Here, we show that the steroid hormone ecdysone controls the expression of the pattern recognition receptor PGRP-LC in Drosophila, thereby tightly regulating innate immune recognition and defense against bacterial infection. We identify a group of steroid-regulated transcription factors as well as two GATA transcription factors that act as repressors and activators of the immune response and are required for the proper hormonal control of PGRP-LC expression. Together, our results demonstrate that Drosophila use complex mechanisms to modulate innate immune responses, and identify a transcriptional hierarchy that integrates steroid signalling and immunity in animals.

Background: The infant mortality rate (IMR), defined as the number of deaths in children under 1 year of age per 1000 live births, is regarded as a sensitive measure of population health (Blaxter). This reflects the overlap between those societal factors that impact infant mortality and those that affect the health of the larger community, such as SES, nutrition, living conditions, education, employment and access to health care. In 2003, Reidpath et al showed a strong linear relation between IMR and the disability adjusted life expectancy (DALE), a more comprehensive measure of population health. They concluded that either the IMR or the DALE could stand as a proxy for the measurement of population health.

Objectives: We proposed to study historic trends in the IMR of the city of Worcester, MA, the second largest city in New England with a population of 181,045 (census 2010), over a 100 year period. We evaluated trends in the overall infant mortality rate as well as by specific causes of death. We further looked at known changes in medical innovation as well as community living conditions that may have had an effect on these rates.

Methods: From August through September 2012, infant death certificates housed in the Worcester City Hall, Office of the City Clerk, were reviewed and entered into an Excel spreadsheet. The first year, 1906, was selected due to a particularly high IMR. Following 1906, years were chosen at 10-year intervals through 1976. Beginning in 1986, data was available through a downloadable file. Data collected included the record number, the date of death, the age of the infant in months and years, cause of death, city of residence, and place of birth of mother. Specific causes of death were transformed into 13 general categories. A subsequent comparative analysis was performed.

Results: A total of 2929 hard copy death certificates were reviewed and an additional 116 records were added through downloadable files. Because 1956 was the last year to include stillbirth in infant mortality records, analysis was conducted excluding numbers of stillbirths. In 1906, the overall IMR was 143 (per 1000 live births). By 1936, the total IMR had already dropped significantly to 52, a drop of 64%. By 2006, the IMR had dropped to 4.6, a decrease of almost 97%. Much of this drop reflected changes in the IMR due to infection, which dropped from 75 in 1906 to 15 in 1936 and to .4 by 2006. In total, the decrease in IMR due to infection was responsible for more than half of the total decrease in IMR, with 80% of the drop in infection-related IMR occurring before 1936. Over this time period, the IMR due to congenital malformations also slowly decreased from 8 in 1906, to 7.3 in 1976 and then to 2.0 in 1986 and .8 in 2006. Interestingly, 83% of the decreases in IMR due to malformation occurred after 1976. IMR due to prematurity was 34 in 1906, decreased to 14.7 in 1976 and further decreased to 6.4 in 1986 and to 3.1 in 2006. Again, 89% of the decreases in IMR due to prematurity occurred after 1976.

Conclusions: The IMR in Worcester has undergone a dramatic reduction over the past 100 years, driven in large part by great reductions in number of deaths from infectious causes. Interestingly, a large part of the reduction in IMR secondary to infection occurred by 1936, prior to the development and widespread availability of antibiotics and vaccines against infectious diseases starting in the 1940s. Changes in public health infrastructure, changes in hygiene, including water, sewage and housing, and access to better nutrition and education likely played a significant role in decreased infant mortality due to infection prior to the development of medical interventions. A number of medical developments are likely responsible for decreased rates of infant mortality due to malformations and prematurity seen after 1976. These include the advent of neonatal surgery in the 1950s, the introduction of Neonatal Intensive Care Units (NICUs) in the 1960s, the use of fetal heart monitors and fetal distress as an indication for delivery by cesarean section in the 1960s to 1970s, the development of amniocentesis (for lung maturity and genetic testing) and ultrasound (for dating) in the 1970s, Roe vs. Wade in 1973, the advent of alpha fetoprotein testing and folic acid supplementation in the 1980s, and corticosteroids for fetal lung maturity in the 1980s-1990s. The large decrease in IMR due to infectious causes over the last 100 years highlights IMR’s sensitive relationship to societal factors and suggests that deteriorations in living conditions during recent difficult economic times could result in high and increasing IMRs among vulnerable subpopulations. We propose that interventions addressing societal factors could have the greatest impact in preventing infant mortality in Worcester.

Background: Heart failure is a highly prevalent, morbid, and costly disease with a poor long-term prognosis. Evidence-based therapies utilized over the past 2 decades hold the promise of improved outcomes, yet few contemporary studies have examined survival trends in patients with acute heart failure.

Objectives: The primary objective of this population-based study was to describe trends in short and long-term survival in patients hospitalized with acute decompensated heart failure (ADHF). A secondary objective was to examine patient characteristics associated with decreased long-term survival.

Methods and Results: We reviewed the medical records of 9,748 patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004. Patients hospitalized with ADHF were more likely to be elderly and to have been diagnosed with multiple comorbidities in 2004 compared with 1995. Over this period, survival was significantly improved in-hospital, and at 1, 2, and 5 years post-discharge. Five-year survival rates increased from 20% in 1995 to 28% in 2004. Although survival improved substantially over time, older patients and patients with chronic kidney disease, chronic obstructive pulmonary disease, anemia, low body mass index, and low blood pressures had consistently lower post-discharge survival rates than patients without these comorbidities.

Conclusion: Between 1995 and 2004, patients hospitalized with ADHF have become older and increasingly comorbid. Although there has been a significant improvement in survival among these patients, their long-term prognosis remains poor, as fewer than 1 in 3 patients hospitalized with ADHF in 2004 survived more than 5 years.

Discusses double diabetes -- the coexistence of features of both type 1 and type 2 diabetes in the same individual -- with a comprehensive discussion of the various aspects of this disorder and a focus on the search for a treatment paradigm in children and adolescents.

Chitin is the second most common polysaccharide found in nature. It is present in crustacean shells, insect exoskeletons, parasitic nematode eggs and gut linings, and in the cell wall of fungi. The deacetylated derivative of chitin, chitosan, is less common but is particularly evident in certain species of fungi, such as Cryptococcus, and the cyst wall of Entamoeba. How mammals sense and respond to these polymers is not well understood, and conflicting reports on their immunological activity have led to some controversy. Despite this, promising translational applications that exploit the unique properties of chitin and chitosan are being developed.

BACKGROUND: Although popular clinically, the psychometric properties of motivation rulers for tobacco cessation are unknown. This study examined the psychometric properties of rulers assessing importance, readiness, and confidence in tobacco cessation.

METHODS: This observational study of current smokers was conducted at 10 US emergency departments (EDs). Subjects were assessed during their ED visit (baseline) and reassessed two weeks later. We examined intercorrelations between the rulers as well as their construct and predictive validity. Hierarchical multinomial logistic regressions were used to examine the rulers' predictive ability after controlling for covariables.

RESULTS: We enrolled 375 subjects. The correlations between the three rulers ranged from 0.50 (between Important and Confidence) to 0.70 (between Readiness and Confidence); all were significant (p < 0.001). Individuals in the preparation stage displayed the highest motivation-ruler ratings (all rulers F 2, 363 >/= 43; p < 0.001). After adjusting for covariables, each of the rulers significantly improved prediction of smoking behavior change. The strength of their predictive ability was on par with that of stage of change.

CONCLUSION: Our results provide preliminary support for the psychometric soundness of the importance, readiness, and confidence rulers.