Use of sugammadex in prevention of post-operative urinary retention in minimally invasive hernia surgery.

PURPOSE: Post-operative urinary retention (POUR) is a known complication of hernia surgery. Minimally invasive inguinal hernia repair (IHR) is typically done under general anesthesia with neuromuscular blockade (NMB), which is commonly reversed with an anticholinesterase inhibitor paired with an anticholinergic agent. Sugammadex is a unique NMB reversal agent that does not have to be paired with an anticholinergic. We sought to explore the role of sugammadex in reducing the rate of POUR following these procedures. METHODS: Data were collected retrospectively at a single institution between February 2016 and October 2019. We identified and studied patients who underwent minimally invasive IHR and received either sugammadex or neostigmine/glycopyrrolate for NMB reversal. The primary endpoint was POUR requiring bladder catheterization. Secondary endpoints included post-operative and 30-day readmissions. RESULTS: 274 patients were included in this study (143 received neostigmine and glycopyrrolate, 131 sugammadex). The sugammadex patients were on average 5 years older than the neostigmine/ glycopyrrolate patients (63.2 vs 58.2, p = 0.003), and received less median intravenous fluids (IVF) (900 ml vs 1000 ml; p = 0.015). There was a significant difference in the rate of POUR between the sugammadex and neostigmine/glycopyrrolate patients (0.0% vs 8.4%, p ≤ 0.001). The difference remained significant after controlling for age and IVF. The odds of POUR for those who received neostigmine/glycopyrrolate were 25 × higher than the odds of those who received sugammadex. CONCLUSION: The results of this study reflect the protective role of sugammadex against POUR in minimally invasive IHR cases.

SP rTaTME: initial clinical experience with single-port robotic transanal total mesorectal excision (SP rTaTME).

BACKGROUND: The technical difficulty and steep learning curve of transanal total mesorectal excision (taTME) has limited widespread adoption. The single-port (SP) daVinci robot is designed to facilitate single-incision and natural-orifice transluminal endoscopic surgery (NOTES). This paper describes the first clinical experience of single-port robotic taTME (SP rTaTME). METHODS: This was a prospective study on consecutive patients with rectal cancer who underwent SP rTaTME proctosigmoidectomy with handsewn coloanal anastomosis in December 2018 and January 2019. The primary outcome was technical feasibility of the procedure. The secondary outcomes include blood loss, intraoperative complications, length of hospital stay, quality of the TME specimen, short- and long-term morbidity and mortality, as well as short-term oncologic follow -up. RESULTS: There were two patients, a 48-year-old male and a 38-year-old female. Both operations were completed successfully without complications or conversion. Estimated blood loss was 200 mL and 130 mL. In both cases the TME was completed transanally using the SP robot. In the first patient, the abdominal portion was completed through an abdominal single-incision; in the second patient the operation was entirely performed transanally as a pure NOTES procedure. In both cases, the final pathology report showed a complete TME with negative margins. Patients were discharged on postoperative day 3 and 4,respectively. There was no long-term morbidity or mortality. CONCLUSIONS: SP rTaTME is feasible and can be safely performed. It provides excellent optics and dexterity to work in a limited space. Future studies are required to further define the safety profile and the ultimate utility of the SP robot for taTME.

First clinical experience with single-port robotic transanal minimally invasive surgery (SP rTAMIS) for benign rectal neoplasms.

BACKGROUND: The new da Vinci Single-Port (SP) robot is a single-arm four-channel robotic system well suited for endoluminal surgery. We report our initial experience performing SP robotic transanal minimally invasive surgery (SP rTAMIS) for rectal neoplasms. METHODS: Under Institutional Review Board approval, two patients with rectal neoplasms were prospectively enrolled for elective SP rTAMIS. The primary endpoint was to report the safety and feasibility of successful procedure completion with the SP robot. Secondary endpoints included patient characteristics and perioperative metrics. RESULTS: Both patients underwent successful SP rTAMIS resection of rectal neoplasms without intraoperative complications or conversions. The lesions were 4.0 cm and 3.0 cm in size, located 6 cm and 7 cm cephalad to the anorectal ring. Excisions were full thickness with no piecemeal extractions or specimen fragmentation. Estimated blood loss was 0 mL and 30 mL. The mean excised area was 13.4 cm2 (22.7 cm2 and 9.0 cm2). The mean docking time was 5.25 min (range 2-8 min) and mean console time was 122.5 min (98 min and 147 min). Patients tolerated a liquid diet on postoperative day (POD) 0 and were discharged on POD 1 after tolerating a low residue diet and having bowel function. Pathology showed two adenomas with negative margins. There was no immediate or delayed morbidity or mortality. CONCLUSIONS: Our initial experience indicates that SP rTAMIS is a safe and feasible approach for local excision of rectal lesions. While SP rTAMIS is very promising, more experience with this approach is necessary to determine its widespread applicability.

rSILS: initial clinical experience with single-port robotic (SPr) right colectomy.

BACKGROUND: The da Vinci Single-Port (SP) robot is a novel platform designed to facilitate single-incision robotic surgery (rSILS). The objective of this study was to describe our initial experience using this platform for SP robotic (SPr) right colectomy. METHODS: Under a Food and Drug Administration-regulated feasibility study and Institutional Review Board approval, a patient with cecal adenocarcinoma underwent an SPr right colectomy. The primary endpoint was the safety and feasibility of the first SPr right colectomy performed in the USA. Secondary endpoints included perioperative metrics, morbidity and mortality. RESULTS: An SPr Standard right colectomy was performed through a 4-cm single incision without the need for conversion or additional port placement. Estimated blood loss was 100 mL and there were no intraoperative complications. The robot was docked once with a docking time of 19 min. Total console time was 116 min and operative time was 219 min. The patient tolerated clear liquids on postoperative day (POD) 0 and a low-residue diet on POD 1. The patient had flatus and a bowel movement on POD 1. She was discharged home on POD 3. Final pathology showed pT3N0 cecal adenocarcinoma with negative margins and 0/24 lymph nodes positive for disease. CONCLUSIONS: Our initial experience demonstrates that an SPr right colectomy is feasible and can be safely completed. We completed an oncologic resection of a cecal adenocarcinoma without complications. The SP robot facilitates the utilization of robotic technology in a single-incision platform to perform colorectal procedures and offers promising benefits in the advancement of robotic surgery.

Antimicrobial light-activated materials: towards application for food and environmental safety.

AIMS: To produce light-activated antimicrobial materials composed of the photodynamic dye phloxine B incorporated into paper or cellulose membranes and to investigate ability of these materials to decrease bacterial loads on their surfaces as well as on food surfaces that were in contact with these materials under illumination with regular white light. METHODS AND RESULTS: Antimicrobial cellulose-based materials with incorporated phloxine B were produced using a layer-by-layer deposition method. Antimicrobial properties of the materials were tested in model systems as well as for decontamination of food and food contact surfaces. Pseudomonas aeruginosa, Listeria monocytogenes and Bacillus anthracis were efficiently killed by exposure of the bacterial suspension to the dye-containing material under illumination with white light, but Salmonella Typhimurium and Escherichia coli O157:H7 were only partially affected. Application of the materials for decontamination of food surfaces artificially contaminated with L. monocytogenes was shown to be ineffective, while the self-decontamination of the material surface by exposure to white light resulted in eradication of L. monocytogenes cells from the material surface. CONCLUSIONS: The developed materials showed significant self-decontaminating ability when under illumination; however, decontamination of food surfaces in contact with the developed materials was not achieved. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrates the antibacterial activity of materials with incorporated photodynamic dyes when under illumination with regular-intensity white light. Possible uses of the light-activated antimicrobial materials for food processing, as food contact surfaces, and surfaces in public areas to prevent cross-contamination are discussed.

Biological complexity and drug discovery: a practical systems biology approach.

Drugs fail in clinical studies most often from lack of efficacy or unexpected toxicities. These failures result from an inadequate understanding of drug action and follow, in part, from our dependence on drug discovery technologies that do not take into account the complexity of human disease biology. Biological systems exhibit many features of complex engineering systems, including modularity, redundancy, robustness, and emergent properties. Addressing these features has contributed to the successful design of an improved biological assay technology for inflammation drug discovery. This approach, termed Biologically Multiplexed Activity Profiling (BioMAP), involves the statistical analysis of protein datasets generated from novel complex primary human cell-based assay systems. Compound profiling in these systems has revealed that a surprisingly large number of biological mechanisms can be detected and distinguished. Features of these assays relevant to the behaviour of complex systems are described.

Rules of chemokine receptor association with T cell polarization in vivo.

Current concepts of chemokine receptor (CKR) association with Th1 and Th2 cell polarization and effector function have largely ignored the diverse nature of effector and memory T cells in vivo. Here, we systematically investigated the association of 11 CKRs, singly or in combination, with CD4 T cell polarization. We show that Th1, Th2, Th0, and nonpolarized T cells in blood and tissue can express any of the CKRs studied but that each CKR defines a characteristic pool of polarized and nonpolarized CD4 T cells. Certain combinations of CKRs define populations that are markedly enriched in major subsets of Th1 versus Th2 cells. For example, although Th0, Th1, and Th2 cells are each found among blood CD4 T cells coordinately expressing CXCR3 and CCR4, Th1 but not Th2 cells can be CXCR3(+)CCR4(-), and Th2 but only rare Th1 cells are CCR4(+)CXCR3(-). Contrary to recent reports, although CCR7(-) cells contain a higher frequency of polarized CD4 T cells, most Th1 and Th2 effector cells are CCR7(+) and thus may be capable of lymphoid organ homing. Interestingly, Th1-associated CKRs show little or no preference for Th1 cells except when they are coexpressed with CXCR3. We conclude that the combinatorial expression of CKRs, which allow tissue- and subset-dependent targeting of effector cells during chemotactic navigation, defines physiologically significant subsets of polarized and nonpolarized T cells.

Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential.

Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. IL-12 enhances this dendritic cell-dependent upregulation, while IL-4 inhibits it. In blood, 35-56% of Bonzo+ CD4 T cells are Th1 cells, and 60-65% of Bonzo+ CD8 T cells are Tc1 cells, while few Bonzo+ cells are type 2 T cells. Almost all Bonzo+ Tc1 cells contain preformed granzyme A and display cytotoxic effector phenotype. Most Bonzo+ T cells lack L-selectin and/or CCR7, homing receptors for lymphoid tissues. Instead, Bonzo+ T cells are dramatically enriched among T cells in tissue sites of inflammation, such as rheumatoid joints and inflamed livers. Bonzo may be important in trafficking of effector T cells that mediate type 1 inflammation, making it a potential target for therapeutic modulation of inflammatory diseases.

CCR7 expression and memory T cell diversity in humans.

CCR7, along with L-selectin and LFA-1, mediates homing of T cells to secondary lymphoid organs via high endothelial venules (HEV). CCR7 has also been implicated in microenvironmental positioning of lymphocytes within secondary lymphoid organs and in return of lymphocytes and dendritic cells to the lymph after passage through nonlymphoid tissues. We have generated mAbs to human CCR7, whose specificities correlate with functional migration of lymphocyte subsets to known CCR7 ligands. We find that CCR7 is expressed on the vast majority of peripheral blood T cells, including most cells that express adhesion molecules (cutaneous lymphocyte Ag alpha(4)beta(7) integrin) required for homing to nonlymphoid tissues. A subset of CD27(neg) memory CD4 T cells from human peripheral blood is greatly enriched in the CCR7(neg) population, as well as L-selectin(neg) cells, suggesting that these cells are incapable of homing to secondary lymphoid organs. Accordingly, CD27(neg) T cells are rare within tonsil, a representative secondary lymphoid organ. All resting T cells within secondary lymphoid organs express high levels of CCR7, but many activated cells lack CCR7. CCR7 loss in activated CD4 cells accompanies CXC chemokine receptor (CXCR)5 gain, suggesting that the reciprocal expression of these two receptors may contribute to differential positioning of resting vs activated cells within the organ. Lymphocytes isolated from nonlymphoid tissues (such as skin, lung, or intestine) contain many CD27(neg) cells lacking CCR7. The ratio of CD27(neg)/CCR7(neg) cells to CD27(pos)/CCR7(pos) cells varies from tissue to tissue, and may correlate with the number of cells actively engaged in Ag recognition within a given tissue.

Management of the agitated patient.

Unfortunately, although delirium is common in the general hospital, the diagnosis is frequently missed. As delirium often indicates a serious, sometimes life-threatening, medical or surgical condition, successful management and subsequent prevention of morbidity and mortality require prompt recognition and early intervention. Failure to recognize, diagnose, and treat delirium and the underlying pathology can result in death. This article presents current thinking on the management of delirium and related agitation in the general medical hospital.

Depression in Korean immigrants with hepatitis B and related liver diseases.

The authors evaluated 50 Korean immigrants who had chronic viral hepatitis or who were healthy carriers for the hepatitis B virus in terms of the relationships between their depression scores, psychosocial stressors, social support, and biological markers of dysfunction. All participants completed a questionnaire, describing their worries and concerns, and the shortform of the Beck Depression Inventory (BDI-sf). Hepatic transaminases, albumin levels, and prothrombin times were measured during routine clinic follow-up visits and were abstracted from the medical record. Values recorded within 3 months before and within 3 months after the psychiatric interview were correlated with BDI scores. BDI-sf total scores were significantly associated with transaminase elevations (P<0.001) both before and after BDI-sf administration. BDI scores were not associated with other measures of liver dysfunction or other medical causes of depression. Patients with higher BDI-sf total scores had more psychosocial stressors (P = 0.008) and lower Global Assessment of Functioning (GAF) scores (P = 0.000).

Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity.

The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4(+) and CD8(+) T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9(-). TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.

Preparatory education for informed decision-making in prostate cancer early detection and treatment.

Patients are expected to assume increased responsibility for self-management in health care. However, little attention has been directed to the problem of preparing individuals to play a more active role in the physician-patient relationship. Preparatory education about prostate cancer early detection and treatment is needed to enable patients to recognize the importance of their role in medical decision-making, voice personal values and preferences related to health care choices, and make informed choices under conditions of uncertainty about possible outcomes. Effective decision aids are needed to facilitate shared decision-making in the context of the physician-patient relationship along the continuum of prostate cancer care. Decision aids for patients have taken the form of informational booklets, scripted telephone counseling, decision boards, educational videotapes, interactive videodiscs, computer programs, and Internet Web sites. The impact of preparatory education and the use of decision aids should be evaluated in terms of change in knowledge and understanding, shifts in decision preferences, health care utilization, and satisfaction with care. The need for this type of patient interaction will grow as technology increases patient access to health care information.

Communicating effectively with the patient and family about treatment options for prostate cancer.

To help the patient with prostate cancer, his family, and his friends, in coping with the diagnosis and its treatment, health care providers need to understand the controversies about treatment options and the impact that such controversies have on medical decision-making. To update health care providers, the authors reviewed all pertinent citations in the medicine database from 1966 to 2000, and in other relevant publications. These resources are also available to our patients through the Internet and other avenues, such as books and magazines. It is the role of the physician to counsel patients about their individual circumstances to allow them to make the best individualized treatment option. Patients who have appropriate information and are actively involved with the decision-making process are, in general, psychologically healthier. Though watchful waiting has no side effects, men must cope psychologically with issues of long-term cancer survivorship. With early detection, men can choose between different treatment options (eg, radiation versus radical prostatectomy). Urinary incontinence, sexual dysfunction, and fatigue are major emotional and physical stressors for this population. Providers of care need to be aware of the psychosocial sequelae of prostate cancer and treatment-related side effects and assist their patients in processing ever-growing data on the management of prostate cancer that technology brings.

A novel chemokine ligand for CCR10 and CCR3 expressed by epithelial cells in mucosal tissues.

Mucosae-associated epithelial chemokine (MEC) is a novel chemokine whose mRNA is most abundant in salivary gland, with strong expression in other mucosal sites, including colon, trachea, and mammary gland. MEC is constitutively expressed by epithelial cells; MEC mRNA is detected in cultured bronchial and mammary gland epithelial cell lines and in epithelia isolated from salivary gland and colon using laser capture microdissection, but not in the endothelial, hemolymphoid, or fibroblastic cell lines tested. Although MEC is poorly expressed in skin, its closest homologue is the keratinocyte-expressed cutaneous T cell-attracting chemokine (CTACK; CCL27), and MEC supports chemotaxis of transfected lymphoid cells expressing CCR10, a known CTACK receptor. In contrast to CTACK, however, MEC also supports migration through CCR3. Consistent with this, MEC attracts eosinophils in addition to memory lymphocyte subsets. These results suggest an important role for MEC in the physiology of extracutaneous epithelial tissues, including diverse mucosal organs.

Constant observation practices in the general hospital setting: a national survey.

The authors conducted a national survey of 355 general medical/surgical hospitals to assess constant observation (CO) practices. The authors assessed overall use, expense, staffing patterns, funding strategies, and cost-saving interventions. Virtually all responding hospitals (N = 102) reported using some form of CO. Several hospitals reported significant decreases in CO expenditures after the implementation of cost-saving interventions (the largest annual decrease reported was $340,000). Cost-saving interventions included utilizing consolidated bed spaces, relocating patients near nursing stations, placing at-risk patients in bed enclosure devices, and regularly assisting patients to the toilet. In addition, less costly personnel were hired, and volunteers and/or patient family members provided CO (or were required to assist with the cost of CO). Finally, hospital staff were educated about the costs and the appropriate use of CO. They were also taught to recognize and effectively treat delirium.

African-American men and intention to adhere to recommended follow-up for an abnormal prostate cancer early detection examination result.

OBJECTIVES: To assess the intention of African-American men to have the recommended follow-up in the event of an abnormal prostate cancer early detection examination and to identify the variables that help to explain adherence intention. METHODS: In the spring of 1995, we selected a random sample of 548 African-American men who were patients at the University of Chicago Health Service. The sample included men who were 40 to 70 years of age, did not have a personal history of prostate cancer, and had a working telephone number. A total of 413 men who completed the telephone survey received an invitation to consider undergoing a prostate cancer early detection examination. The survey provided data on personal background characteristics, knowledge, attitudes, and beliefs related to prostate cancer and early detection. Respondents were asked whether they would choose to have the recommended follow-up in the event of an abnormal early detection examination result. Univariate and multivariate analyses of intention to have follow-up were performed. RESULTS: An intention to have the recommended follow-up was reported by 77% of the survey respondents. The results of multivariate analyses revealed that the intention to have the follow-up was positively associated with education beyond high school (odds ratio [OR] 1.9); perceived self-efficacy related to prostate cancer screening (OR 2.1); the belief that prostate cancer can be cured (OR 3.3); the belief that prostate cancer screening should be done in the absence of prostate problems (OR 2.3); and physician support for prostate cancer screening (OR 2.1). CONCLUSIONS: African-American men who have a high school education or less may be at risk of nonadherence to recommended follow-up. Adherence also may be low among men who do not have favorable views of early detection or do not perceive strong physician support for early detection. Research is needed to determine whether intention and other factors predict actual adherence to follow-up in this population group.

Biopsychosocial aspects of prostate cancer.

Prostate cancer early detection choices and treatment options are fraught with controversy. To update the consultation-liaison psychiatrist who works with at-risk men, the authors reviewed all pertinent citations in the medicine database from 1966 to 1998 and in other relevant publications. Though watchful waiting for early-stage prostate cancer has no side effects, men must cope psychologically with issues of long-term cancer survivorship. Men can choose between different treatment options (e.g., radiation vs. radical prostatectomy) with early detection. Urinary incontinence, sexual dysfunction, and fatigue are major emotional and physical stressors for this population. Consultation-liaison psychiatrists and physicians need to be aware of the psychosocial sequelae of both prostate cancer and treatment-related side effects.

Leukocyte arrest during cytokine-dependent inflammation in vivo.

Leukocyte rolling along the walls of inflamed venules precedes their adhesion during inflammation. Rolling leukocytes are thought to arrest by engaging beta2 integrins following cellular activation. In vitro studies suggest that chemoattractants may instantaneously activate and arrest rolling leukocytes. However, how leukocytes stop rolling and become adherent in inflamed venules in vivo has remained rather mysterious. In this paper we use a novel method of tracking individual leukocytes through the microcirculation to show that rolling neutrophils become progressively activated while rolling down the venular tree. On average, leukocytes in wild-type mice roll for 86 s (and cover 270 microm) before becoming adherent with an efficiency around 90%. These rolling leukocytes exhibit a gradual beta2 integrin-dependent decrease in rolling velocity that correlates with an increase in intracellular free calcium concentration before arrest. Similar tracking analyses in gene-targeted mice demonstrate that the arrest of rolling leukocytes is very rare when beta2 integrins are absent or blocked by a mAb. Arrest is approximately 50% less efficient in the absence of E-selectin. These data suggest a model of leukocyte recruitment in which beta2 integrins play a critical role in stabilizing leukocyte rolling during a protracted cellular activation period before arrest and firm adhesion.

St. John's Wort.

OBJECTIVE: The objective of this article is to review the current knowledge of the pharmacology, sites of action, and therapeutic effectiveness of St. John's Wort. METHOD: The method used was a review of the available literature, using keywords to search the medline database. Bibliographies of the papers, thus obtained, were searched for further documents not referenced by medline. We reviewed papers from this collection. RESULTS: This review reveals that most of the available data on efficacy and safety of St. John's Wort involve its use in mild to moderate depression. Much, but not all of the prevailing opinion is positive. Nevertheless, the quality of therapeutic trials vary so greatly that definitive conclusions are not possible. Both the source and mode of St. John's Wort's therapeutic effect are unclear. We need further controlled studies of effectiveness, safety, and mode of action. In addition to its use in depression, there are reports suggesting possible therapeutic effects in other conditions such as certain malignancies and infections, but these are far too preliminary to permit any conclusions.