SAGES masters program: the top 10 seminal articles for the laparoscopic left and sigmoid colectomy pathway for complex disease.

BACKGROUND: The SAGES University Colorectal Masters Program is a structured educational curriculum that is designed to aid practicing surgeons develop and maintain knowledge and technical skills for laparoscopic colorectal surgery. The Colorectal Pathway is based on three anchoring procedures (laparoscopic right colectomy, laparoscopic left and sigmoid colectomy for uncomplicated and complex disease, and intracorporeal anastomosis for minimally invasive right colectomy) corresponding to three levels of performance (competency, proficiency and mastery). This manuscript presents focused summaries of the top 10 seminal articles selected for laparoscopic left and sigmoid colectomy for complex benign and malignant disease. METHODS: A systematic literature search of Web of Science for the most cited articles on the topic of laparoscopic complex left/sigmoid colectomy yielded 30 citations. These articles were reviewed and ranked by the SAGES Colorectal Task Force and invited subject experts according to their citation index. The top 10 ranked articles were then reviewed and summarized, with emphasis on relevance and impact in the field, study findings, strength and limitations and conclusions. RESULTS: The top 10 seminal articles selected for the laparoscopic left/sigmoid colectomy for complex disease anchoring procedure include advanced procedures such as minimally invasive splenic flexure mobilization techniques, laparoscopic surgery for complicated and/or diverticulitis, splenic flexure tumors, complete mesocolic excision, and other techniques (e.g., Deloyers or colonic transposition in cases with limited colonic reach after extended left-sided resection). CONCLUSIONS: The SAGES Colorectal Masters Program top 10 seminal articles selected for laparoscopic left and sigmoid colectomy for complex benign and malignant disease anchoring procedure are presented. These procedures were the most essential in the armamentarium of practicing surgeons that perform minimally invasive surgery for complex left and sigmoid colon pathology.

Detection of Newly Secreted Antibodies Predicts Nonrecurrence in Primary Clostridioides difficile Infection.

Within 8 weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no clear clinical correlates or validated biomarkers that can predict recurrence during primary infection. This study demonstrated the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence. Forty-six hospitalized CDI patients were enrolled at Emory University Hospitals. Samples of serum and a novel matrix from circulating plasmablasts called "medium-enriched for newly synthesized antibodies" (MENSA) were collected during weeks 1, 2, and 4. Antibodies specific for 10 C. difficile antigens were measured in each sample. Among the 46 C. difficile-infected patients, 9 (19.5%) experienced recurrence within 8 weeks of primary infection. Among the 37 nonrecurrent patients, 23 (62%; 23/37) had anti-C. difficile MENSA antibodies specific for any of the three toxin antigens: TcdB-CROP, TcdBvir-CROP, and/or CDTb. Positive MENSA responses occurred early (within the first 12 days post-symptom onset), including six patients who never seroconverted. A similar trend was observed in serum responses, but they peaked later and identified fewer patients (51%; 19/37). In contrast, none (0%; 0/9) of the patients who subsequently recurred after hospitalization produced antibodies specific for any of the three C. difficile toxin antigens. Thus, patients with a negative early MENSA response against all three C. difficile toxin antigens had a 19-fold greater relative risk of recurrence. MENSA and serum levels of immunoglobulin A (IgA) and/or IgG antibodies for three C. difficile toxins have prognostic potential. These immunoassays measure nascent immune responses that reduce the likelihood of recurrence thereby providing a biomarker of protection from recurrent CDI. Patients who are positive by this immunoassay are unlikely to suffer a recurrence. Early identification of patients at risk for recurrence by negative MENSA creates opportunities for targeted prophylactic strategies that can reduce the incidence, cost, and morbidity due to recurrent CDI.

Development of a focal lesion phantom with clinically relevant lesion characteristics for image quality evaluation of breast ultrasound scanners.

PURPOSE: Contrast-detail (C-D) and anechoic-target (A-T) detectability are measures of an ultrasound scanner's ability to image lesions of varying contrast and size from background tissue and, as such, they are important tools for grading the imaging capabilities of ultrasound scanners. The objective of this study was to develop a range of contrast- and anechoic-detail phantoms with clinically relevant lesions, of various contrast and sizes, for performance testing of breast ultrasound equipment. METHODS: Tissue mimicking materials that represent the acoustic properties of breast fibroglandular tissue were produced and moulded to construct a range of C-D and A-T phantoms. Two phantom designs were produced, containing cylindrical and spherical targets. Both phantom types were constructed with contrast targets covering the range anechoic, -1, -2, -3 and -4 dB, with lesion diameters of 1-4 mm, positioned at four clinically relevant depths (10, 25, 40 and 55 mm). An image analysis program was developed to objectively analyse the lesion images and to determine the lesion-signal-noise-ratio (LSNR). RESULTS: Both phantoms were used to evaluate the performance of a breast ultrasound scanner. The use of cylindrical phantoms led to an artificially higher image quality performance compared with the more clinically relevant spherical lesion phantom, thus indicating the importance of using the appropriate targets in ultrasound phantoms. CONCLUSION: The spherical lesion phantoms, coupled with the quantitative metric of LSNR, provides a comprehensive approach for performance and quality control testing, as well as the evaluation of advanced ultrasound imaging modes and technologies.

Novel immunoassay for diagnosis of ongoing Clostridioides difficile infections using serum and medium enriched for newly synthesized antibodies (MENSA).

BACKGROUND: Clostridioides difficile infections (CDI) have been a challenging and increasingly serious concern in recent years. While early and accurate diagnosis is crucial, available assays have frustrating limitations. OBJECTIVE: Develop a simple, blood-based immunoassay to accurately diagnose patients suffering from active CDI. MATERIALS AND METHODS: Uninfected controls (N = 95) and CDI patients (N = 167) were recruited from Atlanta area hospitals. Blood samples were collected from patients within twelve days of a positive CDI test and processed to yield serum and PBMCs cultured to yield medium enriched for newly synthesized antibodies (MENSA). Multiplex immunoassays measured Ig responses to ten recombinant C. difficile antigens. RESULTS: Sixty-six percent of CDI patients produced measurable responses to C. difficile antigens in their serum or MENSA within twelve days of a positive CDI test. Fifty-two of the 167 CDI patients (31%) were detectable in both serum and MENSA, but 32/167 (19%) were detectable only in MENSA, and 27/167 (16%) were detectable only in serum. DISCUSSION: We describe the results of a multiplex immunoassay for the diagnosis of ongoing CDI in hospitalized patients. Our assay resolved patients into four categories: MENSA-positive only, serum-positive only, MENSA- and serum-positive, and MENSA- and serum-negative. The 30% of patients who were MENSA-positive only may be accounted for by nascent antibody secretion prior to seroconversion. Conversely, the serum-positive only subset may have been more advanced in their disease course. Immunocompromise and misdiagnosis may have contributed to the 34% of CDI patients who were not identified using MENSA or serum immunoassays. IMPORTANCE: While there was considerable overlap between patients identified through MENSA and serum, each method detected a distinctive patient group. The combined use of both MENSA and serum to detect CDI patients resulted in the greatest identification of CDI patients. Together, longitudinal analysis of MENSA and serum will provide a more accurate evaluation of successful host humoral immune responses in CDI patients.

Community Priority setting for Fetal Alcohol Spectrum Disorder Research in Australia.

INTRODUCTION: Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder caused by prenatal alcohol exposure (PAE). FASD research is a rapidly growing field that crosses multiple disciplines. To ensure research is relevant and meaningful for people living with FASD, their families, and the broader public there is a need to engage community members in setting priorities for research. OBJECTIVES: Our primary objective was to formally identify the views of people living with FASD, their parents/caregivers, service providers, and the general community on the research priorities for FASD and alcohol use in pregnancy in Australia. Our secondary objective was to provide an overview of current research in the highest priority areas identified. METHODS: The approach for this study involved two community surveys and a consensus workshop, followed by a rapid literature review. Survey responses (n = 146) were collected and grouped using qualitative thematic analysis. The themes identified were then ranked in a second survey (n = 45). The 22 highest ranked themes were considered in a workshop with 21 community members, and consensus on the top ten priority areas was sought. The priority areas were grouped into conceptually similar topics and rapid literature reviews were undertaken on each. RESULTS: A diverse range of priorities was identified within key areas of prevention, diagnosis, and therapy. On request from participants, separate priority lists were developed by Aboriginal and non-Aboriginal participants. CONCLUSION: There is need for a national network of researchers to take forward the research commenced by the Centre of Research Excellence, FASD Research Australia, in addressing community priorities. KEY WORDS: Community, priorities, FASD, rapid review, Australia.

Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17.

Linkage analysis of 15 Utah kindreds demonstrated that a gene responsible for von Recklinghausen neurofibromatosis (NF) is located near the centromere on chromosome 17. The families also gave no evidence for heterogeneity, indicating that a significant proportion of NF cases are due to mutations at a single locus. Further genetic analysis can now refine this localization and may lead to the eventual identification and cloning of the defective gene responsible for this disorder.

The effect of pre-operative counselling on smoking patterns in patients undergoing forefoot surgery.

BACKGROUND: Smoking contributes to higher surgical complication rates. Previous studies assessing smoking cessation interventions examined the provision of comprehensive packages. The use of surgery as an incentive to complement brief advice has not been fully evaluated. METHODS: Smokers were counselled and referred to their general practitioners for specific cessation strategies. Smoking status was recorded prior to surgery, on admission and in post-operative clinics. A telephone survey at a mean of 12 months post-operation ascertained long-term behavioural changes. RESULTS: Ninety-seven patients underwent surgery with twenty-five recorded as smokers. Sixteen stopped smoking pre-operatively; a further four reduced their intake, as a direct consequence of counselling. No patients were previously aware of the detrimental effects of smoking associated with foot surgery. CONCLUSIONS: Surgery provides an incentive for smoking cessation, maintained post-operatively. Although forefoot fusions and arthrodeses were used in our study, the results are transferable to other branches of orthopaedic surgery.

The use of post-operative reverse camber shoes following scarf osteotomy.

BACKGROUND: Reverse camber shoes are a popular choice for immobilization following scarf osteotomy. There are no reports in the literature giving guidance on the duration of shoe use. METHODS: Seventy-eight patients were reviewed. All had been advised to remain in reverse camber shoes until point of radiographic follow up. Data regarding time spent in shoes, associated adverse symptoms of shoes, and complications were recorded. RESULTS: Three groups emerged. Group 1 (65 patients) wore the shoes for the instructed period of time. Group 2 (six patients) were those who removed the shoes early. Group 3 (seven patients) were those who wore the shoes following review. There were no differences in complication rates between the groups. CONCLUSION: The use of post-op shoes is for symptom control. Our practice now is to advise patients to wear their shoes for as long as they feel necessary rather than giving them a prescriptive time limit.

Prevalence of recreational drug use reported by men who have sex with men attending sexual health clinics in Manchester, UK.

Recreational drug use (RDU) has been reported to be disproportionately higher in men who have sex with men (MSM) when compared to their heterosexual counterparts. To identify RDU, links to risky sexual practices and infections for MSM attending three sexual health clinics across Manchester, United Kingdom, a retrospective case note review was conducted using a random powered sample of service users attending three sites during 2014. Three hundred and fifty-seven case notes were reviewed across three sites. Eighteen per cent of service users reported any type of RDU. Use of at least one of the three drugs associated with chemsex (crystal methamphetamine, mephedrone, gamma hydroxybutyrate/gamma butyrolactone) was reported by 3.6%. A statistically significant difference was identified between non-drug users and any-drug users reporting: group sex (odds ratio [OR] 5.88, p = 0.013), condomless receptive anal intercourse (CRAI) (OR 2.77, p = 0.003) and condomless oral intercourse (OR 2.52, p = 0.016). A statistically significant difference was identified between chemsex-related drug user and non-drug user groups reporting: group sex (OR 13.05, p = 0.023), CRAI (OR 3.69, p = 0.029) and condomless insertive anal intercourse (OR 1.27, p = 0.039). There was also a statistically higher incidence of gonorrhoea infection in chemsex-related drug use compared with those not using drugs (p = 0.002, OR 6.88). This study identifies that substance use is common in MSM attending sexual health clinics in Manchester. High-risk sexual practices and certain sexually transmitted infections are more common in MSM reporting RDU.

Sulfhydryl groups of native myosin and of the myosin heavy chains from Physarum polycephalum compared to vertebrate skeletal, smooth, and non-muscle myosins.

Although a previously reported analysis of Physarum myosin detected no cysteine residues in the molecule, the myosin ATPase activity was inhibited by p-chloromercuribenzoate. We have re-examined this apparently contradictory finding. We found highly purified plasmodial myosin to be very sensitive to N-ethylmaleimide inhibition of the K+, Ca2+ -activated ATPase. An estimate of the number of reactive sulfhydryls of the native myosin using Ellman's reagent showed only 1.5 mol 11 min-reactive sulfhydryl/mol as compared to 4.5 for chicken breast myosin in 5 min. 3H- and 14C-labelled N-ethylmaleimide was used to estimate the total sulfhydryls of the SDS-denatured heavy chains. Plasmodial myosin heavy chains bound 10-13% of the N-ethylmaleimide bound by chicken breast myosin heavy chains. Smooth muscle myosin heavy chains as well as heavy chains of embryonic chicken presumptive myoblasts had 65-70% of the reactive groups of chicken myotube myosin heavy chains. Amino acid analyses of purified Physarum myosin showed that some preparations contained cysteic acid residues even before performic oxidation. After the performic oxidation a mean value of 3 mol cysteic acid per 10(5) g Physarum myosin was found, or less than half that reported for striated muscle myosin. Our results show that in the sulfhydryl-poor plasmodial myosin each heavy chain contains at least two sulfhydryls, and probably more, but that there is variable oxidation of the total sulfhydryls. It has been reported that plasmodial myosin lacks rapidly reacting sulfhydryls groups when tested with an ATP analogue which reacts with light chains of vertebrate muscle myosins. Therefore, the 1-2 sulfhydryls of plasmodial myosin which react rapidly with Ellman's reagent appear to be on the heavy chain. Our results also suggest that during development of myotubes changes occur in the myosin heavy chains.

Heparin after percutaneous intervention (HAPI): a prospective multicenter randomized trial of three heparin regimens after successful coronary intervention.

OBJECTIVES: The purpose of this study was to determine the incidence of bleeding, vascular, and ischemic complications using three different heparin regimens after successful intervention. BACKGROUND: The ideal dose and duration of heparin infusion after successful coronary intervention is unknown. METHODS: Patients were randomized to one of three heparin strategies after coronary intervention: Group 1 (n = 157 patients) received prolonged (12 to 24 h) heparin infusion followed by sheath removal; Group 2 (n = 120 patients) underwent early removal of sheaths, followed by reinstitution of heparin infusion for 12 to 18 h; Group 3 (n = 137 patients) did not receive any further heparin after intervention with early sheath removal. The primary end point of the study was the combined incidence of in-hospital bleeding and vascular events. Secondary end points included in-hospital ischemic events, length of stay, cost and one-month outcome. RESULTS: After successful coronary intervention, 414 patients were randomized. Unstable angina or postinfarction angina was present in 83% of patients before intervention. The combined incidence of bleeding and vascular events was 21% in Group 1, 14% in Group 2 and 8% in Group 3 (p = 0.01). The overall incidence of in-hospital ischemic complications was 2.2%; there were no differences between groups. Length of hospital stay was shorter (p = 0.033) and adjusted hospital cost was lower (p < 0.001) for Group 3. At 30 days, the incidence of delayed cardiac and vascular events was similar for all three groups. CONCLUSIONS: Heparin infusion after successful coronary intervention is associated with more minor bleeding and vascular injury, prolonged length of stay and increased cost. In-hospital and one-month ischemic events rarely occur after successful intervention, irrespective of heparin use. Routine postprocedure heparin is not recommended, even in patients who present with unstable ischemic syndromes.

Prophylaxis of upper gastrointestinal tract bleeding in mechanically ventilated patients. A randomized study comparing the efficacy of sucralfate, cimetidine, and antacids.

Sixty-two mechanically ventilated patients were randomized into three study groups to compare the efficacy of sucralfate vs cimetidine and antacid regimens for the prevention of upper gastrointestinal tract bleeding. Only five study patients (8%) developed bright-red blood per nasogastric tube; four patients received the antacid regimen and one received cimetidine. None of the patients receiving sucralfate developed acute upper gastrointestinal tract bleeding. Bleeding was not severe enough in any patient to require endoscopy or surgery. There were no significant differences in the three groups when several major risk factors for gastrointestinal tract bleeding were analyzed, including sepsis, hypotension, steroid use, adult respiratory distress syndrome, gastric pH of 4 or less, previous peptic ulcer disease, peritonitis, and jaundice. A significantly higher incidence of acute renal failure was noted in the antacid-treated group when compared with the cimetidine and sucralfate groups. We find preliminary evidence that sucralfate is as efficacious as and more cost-effective than either cimetidine or antacids for prophylaxis of stress-related gastrointestinal tract bleeding in the critically ill ventilator-dependent patient.

Rapid and sensitive procedure for assigning idiotypic determinants to heavy or light chains: application to idiotopes associated with the major cross-reactive idiotype of A/J anti-phenylarsonate antibodies.

A rapid and sensitive procedure is described for assigning idiotypic determinants to heavy or light polypeptide chains. Heavy and light chains are resolved by electrophoresis in the presence of sodium dodecyl sulfate. The electrophoretically resolved polypeptides are then transferred to nitrocellulose filters. Filters containing bound heavy and light chains are incubated with 125I-labelled anti-idiotypic antibody, and idiotype-anti-idiotype reactivity visualized by autoradiography. This procedure is illustrated with three monoclonal anti-idiotopic antibodies which recognize determinants associated with the major cross-reactive idiotype family of A/J anti-phenylarsonate antibodies. All three anti-idiotopic antibodies are shown to react with electrophoretically resolved idiotype heavy chain, but not with idiotype light chain.

Relationship between AIDS latency period and AIDS survival time in homosexual and bisexual men.

We identified 277 homosexual and bisexual men diagnosed with acquired immune deficiency syndrome (AIDS) whose estimated human immunodeficiency virus (HIV) seroconversion dates, ranging from 1977-85, could be well approximated. These men were from a cohort of 6,705 homosexual and bisexual men originally recruited for studies of sexually transmitted hepatitis B in San Francisco in 1978-80. We compared the time from HIV seroconversion to the initial disease diagnostic of AIDS (AIDS latency period) with the time from first AIDS diagnosis to death (AIDS survival time) and found no significant overall correlation between latency period and survival time. Both Kaplan-Meier and Cox proportional hazard stepwise analyses found the initial AIDS diagnosis to be significantly associated with latency period, with individuals first diagnosed with Kaposi's sarcoma (KS) having a shorter latency but longer survival than those first diagnosed with Pneumocystis carinii pneumonia (PCP) or other AIDS diagnoses. Individuals with KS tended to be diagnosed earlier in the epidemic compared to those with PCP and other non-KS diagnoses. The AIDS survival time was significantly associated with the initial AIDS diagnosis but not with the estimated year of seroconversion, the year of first AIDS diagnosis, age at seroconversion, or racial/ethnic group. The information presented here on the relationship between the AIDS latency period and survival times suggests a model for the pathogenesis of HIV infection in which there is continual deterioration of the immune system. The wider use of antiviral and prophylactic therapies both preceding and following a diagnosis of AIDS may change this model as both latency and survival times are improved.

Clinical trials of WR-2721 and cis-platinum.

WR-2721 is an aminothiol compound; in the animal model it protects against the nephrotoxicity, neurotoxicity, and hematologic toxicity of cis-platinum. We initiated Phase I trials of WR-2721 and cis-platinum to determine toxicity when WR-2721 was given prior to escalating doses of cis-platinum. With mannitol diuresis and WR-2721, transient nephrotoxicity occurred in 9 of 30 (27%) patients treated with cis-platinum 150 mg/m2 and 7% of patients given with cis-platinum 120 mg/m2. Bone marrow suppression was mild and infrequent. Mild to moderate peripheral neuropathies occurred in 26% of patients courses following a mean cumulative cis-platinum dose of 725 mg/m2. Objective partial responses were observed in 53 of 118 (45%) patients with measurable disease. Antitumor responses were observed in 25 of 53 patients with metastatic melanoma, 12 of 22 patients with locally recurrent or metastatic head and neck cancer, and 7 of 13 patients with metastatic breast cancer refractory to conventional chemotherapy. Controlled studies of WR-2721 and cis-platinum will be performed in the Eastern Cooperative Oncology Group in these disease sites to better define the activity of this regimen and its toxicity.

Prospective evaluation of a stiff shaft glide wire compared with the standard straight wire in crossing severely stenotic aortic valves.

In this prospective randomized study of the use of the Terumo glide wire compared with the standard straight wire for crossing of severely stenotic aortic valves, the glide wire was shown to significantly decrease the fluoroscopy time of the procedure and to lower by 3.4 times the need for crossover to the alternative technique.

Further linkage data on Norrie disease.

We obtained a LOD score of +1.61 using DNA marker L1.28 in 5 generations of a family with Norrie disease, raising the total LOD score to +5.42. There have been no recombinations between the 2 loci in any family to date, making the marker useful for genetic counseling.

Sister chromatid exchange: variation by age, sex, smoking, and breast cancer status.

Variation in sister chromatid exchange (SCE) frequency in lymphocytes of 125 persons was compared using a multivariate general linear model. The study was performed to determine whether SCE frequency differs with respect to age, sex, smoking, and breast cancer status. Study subjects were divided into: members of two branches of families having an excess of cancer (primarily breast) including a brother and sister in one family who developed nonbreast malignancies within 1 yr of the study; women in both families successfully treated for breast cancer (all at least 5 yr posttreatment); and women from the general population with confirmed breast cancer. Controls consisted of spouses who married into the high-risk kindreds, hospital personnel, and others (primarily tradesmen without history of occupational exposure). Results show that: (1) Women with active breast cancer have a significantly higher mean SCE frequency than control women or women greater than 5 yr posttreatment for breast cancer; (2) Cigarette smokers show a significantly higher number of SCEs than was observed in nonsmokers; (3) The increase in SCE level in smokers is dose-related to exposure as measured by cumulative pack-years; (4) SCE values in both high-risk families are not significantly different from controls; (5) Neither the age nor sex of the individual affects SCE frequency; and (6) The observed distribution of exchanges agrees with that expected based on the proportion of the genome represented by each chromosome group.

Cardiac disease in the elderly population.

Cardiovascular disease is the prime cause of disability and death in the elderly population. This article provides a brief review of cardiac physiology in this group as well as a discussion of the acute presentation of myocardial ischemia and infarction, congestive heart failure, vascular dysfunction, and complications of valve replacement.

Dot enzyme-linked immunosorbent assay (Dot-ELISA): comparison with standard ELISA and complement fixation assays for the diagnosis of human visceral leishmaniasis.

The dot enzyme-linked immunosorbent assay (Dot-ELISA), standard ELISA and the complement fixation (CF) tests were compared in the serodiagnosis of African visceral leishmaniasis (kala-azar). Assay sensitivity was determined using sera from 44 patients with parasitologically confirmed kala-azar. Using the Dot-ELISA, 42 of 44 patients (95%) were positive at a reciprocal titer of greater than or equal to 32 (titer range 512-524 288). In the standard ELISA technique, 43 of 44 patients (98%) were positive (titer range 32-32 768). At a reciprocal titer of greater than or equal to 8 in the CF test, 35 patients (80%) were positive, 1 (2%) was negative and 8 patients (18%) showed anticomplementary (AC) activity (titer range 8-2048). Specificity, determined using 33 sera from healthy individuals not living in endemic areas, was 97% in both the Dot-ELISA and the standard ELISA (32 of 33 sera); in he CF test, all sera were negative except 1 (3%) which showed AC activity. Sera from patients with Chagas' disease cross-reacted in the dot-ELISA up to a titer of 512. In the standard ELISA, cross-reactions occurred mainly using sera from patients with Chagas' disease, malaria and syphilis, and to a lesser extent with sera from amebiasis, schistosomiasis and trichinosis patients. Overall titer agreement in replicate experiments was highest in the Dot-ELISA (89%), followed by the standard ELISA (80%) and the CF test (72%).