Chronic variable stress leads to sex specific gut microbiome alterations in mice.

Stress has been implicated in the incidence and severity of psychiatric and gastrointestinal disorders. The immune system is capable of modulating the activity and composition of the gut following stress and vice versa. In this study we sought to examine the sequential relationship between immune signaling and microbiome composition occurring in male and female mice over time using a variable stress paradigm. Tissue was collected prior to, during, and after the stress paradigm from the same mice. Cytokines from plasma and brain were quantified using a multiplexed cytokine assay. Fecal samples were collected at the same timepoints and 16S rRNA amplicon sequencing was performed to determine the relative abundance of microbiota residing in the guts of stressed and control mice. We found sex differences in the response of the gut microbiota to stress following 28 days of chronic variable stress but not 6 days of sub-chronic variable stress. Immune activation was quantified in the nucleus accumbens immediately following Sub-chronic variable when alterations of gut composition had not yet occurred. In both sexes, 28 days of stress induced significant changes in the proportion of Erysipelotrichaceae and Lactobacillaceae, but in opposite directions for male and female mice. Alterations to the gut microbiome in both sexes were associated with changes in cytokines related to eosinophilic immune activity. Our use of an animal stress model reveals the immune mechanisms that may underly changes in gut microbiome composition during and after stress. This study reveals potential drug targets and microbiota of interest for the intervention of stress related conditions.

Association of active smoking on 30-day wound events and additional morbidity and mortality following inguinal hernia repair with mesh: an analysis of the ACHQC database.

BACKGROUND: To date, there is limited data on the association of active smoking and 30-day wound events following inguinal hernia repair (IHR) with mesh. We aimed to determine if active smoking at the time of IHR with mesh was associated with worse 30-days wound events and additional morbidity outcomes using the Abdominal Core Health Quality Collaborative (ACHQC) database. METHODS: All adult patients undergoing elective, IHR with mesh who had 30-day follow-up data available were identified within the ACHQC database. Smokers were defined as having used nicotine within the 30 days prior to surgery. A 1:1 propensity score matched analysis was performed comparing smokers to non-smokers, controlling for factors previously shown to be associated with postoperative wound events. The effect of smoking on 30-day wound events and additional morbidity outcomes following IHR with mesh was investigated using Chi-square or Fisher's exact test for categorical data and Wilcoxon ranked test for continuous data. RESULTS: A total of 17,543 patients met inclusion criteria; 1855 (11%) were active smokers at the time of minimally invasive IHR with mesh. A total of 3694 patients were used for the matched analysis. There were no statistically significant differences between the non-smokers and smokers with respect to the incidence of surgical site infection (p = 0.10), surgical site occurrences (p = 0.22), or surgical site occurrences requiring procedural intervention (p = 0.64). Non-smokers were significantly more likely to be readmitted to the hospital and had significantly less improvement in all pain domains following IHR with mesh. CONCLUSIONS: Active smoking at the time of IHR with mesh is not associated with worse 30-day wound or additional morbidity and mortality outcomes. Based on these results, preoperative smoking cessation for all patients undergoing IHR may not reduce 30-day morbidity.

Ventral hernia repair: an increasing burden affecting abdominal core health.

PURPOSE: To estimate the annual volume and cost of ventral hernia repair (VHR) performed in the United States. METHODS: A retrospective cohort study was performed using the National Inpatient Sample (NIS) and the Nationwide Ambulatory Surgery Sample (NASS) for 2016-2019. Patients over the age of 18 who underwent open (OVHR) or minimally invasive ventral hernia repair (MISVHR) were identified. NIS procedural costs were estimated using cost-to-charge ratios; NASS costs were estimated using the NIS cost-to-charge ratios stratified by payer status. Costs were adjusted for inflation to 2021 dollars using US Bureau of Labor Statistics Consumer Price Index. RESULTS: On average 610,998 VHRs were performed per year. Most were outpatient (67.3% per year), and open (70.7%). MIS procedures increased from 25.8% to 32.8% of all VHRs. Inpatient OVHR had significantly higher associated cost than MISVHR [$35,511 (34,100-36,921) vs. $21,165 (19,664-22,665 in 2019]. Outpatient MISVHR was more expensive than OVHR [$11,558 (11,174-11,942 MIS vs. $6807 (6620-6994) OVHR in 2019]. The estimated cost of an inpatient MISVHR remained similar between 2016 and 2019, from $20,076 (13,374-20,777) to $21,165 (19,664-22,665) and increased slightly from $9975 (9639-10,312) to $11,558 (11,174-11,942) in the outpatient setting. The estimated cost of an inpatient OVHR increased from $31,383 (30,338-32,428) to $35,511 (34,100-36,921), while outpatient costs increased from $6018 (5860-6175) to $6807 (6620-6994). VHR costs decreased slightly over the study period to a mean cost of $9.7 billion dollars in 2019. CONCLUSION: Compared to 2006 national data, VHRs in the United States have almost doubled to 611,000 per year with an estimated annual cost of $9.7 billion. A 1% decrease in VHR achieved through recurrence reduction or hernia prophylaxis could save the US healthcare system at least $139.9 million annually.

Retromuscular drain versus no drain in robotic retromuscular ventral hernia repair: a propensity score-matched analysis of the abdominal core health quality collaborative.

BACKGROUND: Drains may be placed during robotic retromuscular ventral hernia repair (rVHR) to decrease wound morbidity, but their use is controversial. We aimed to assess the impact of retromuscular drain placement on wound morbidity after robotic rVHR. METHODS: Patients with and without drains after robotic rVHR in the Abdominal Core Health Quality Collaborative (ACHQC) registry were compared using a propensity score-matched analysis. Outcomes included surgical site occurrences (SSO), surgical site infections (SSI), and surgical site occurrences requiring procedural interventions (SSOPI) at 30 days. RESULTS: Propensity score matching compared 580 patients with drains to 580 without drains. The groups were well matched with respect to hernia width (drain: 8.0 cm [IQR 6.0; 10.0] vs no drain: 8.0 cm [IQR 5.0; 10.0]; P = 0.399) and transversus abdominis release (drain: 409 (70.5%) vs no drain: 408 (70.3%); P = 0.949). At 30 days, patients with drains had fewer seromas than those without drains (22 (3.8%) vs 88 (15.2%); P < 0.0001). Rates of SSIs and SSOPIs were similar between the two groups at 30 days. Logistic regression analysis showed drain placement lowered the risk of an SSO compared to no drain placement (OR 0.32, CI 0.21-0.47; P < 0.0001). Hospital stay was longer for patients with drains than those without drains (2.0 days [IQR 1.0; 3.0] vs 1.0 day [IQR 1.0; 2.0], respectively; P < .0001). CONCLUSION: Drain placement during robotic rVHR is associated with decreased postoperative seroma occurrence.

Surgery for Complicated Stomal Prolapse: Is the Altemeier Technique an Option? A Report of Three Cases / Cirurgia para prolapso de estoma complicado: A técnica de Altemeier é uma opção? Um relato de três casos

Abstract Introduction The incidence of stomal prolapse ranges from 2% to 22%. The risk factors include colostomy, the short length of the stoma, obesity, emergency surgery, and the improper (or even absence of) marking of the preoperative site for the stoma. Complicated stomal prolapse associated with severe mucosal irritation, ischemic changes, or bleeding requires surgical intervention. Objective To describe the use of the Altemeier technique in the management of cases of complicated prolapsed stoma after failure of the local medical measures and manual reduction. Methods Case series of three patients with past history of abdominoperineal resection of rectal cancer and permanent end colostomy presented with irreducible prolapse of the stoma. After the failure of the local measures and manual reduction, urgent surgical intervention using the modified Altemeier technique was necessary. Results The modified Altemeier technique is simple, presents low risk of operative and postoperative complications, besides enabling an early recovery, with a lower risk of recurrence during the first 6 months after the repair. Conclusion Themodified Altemeier technique may be a valid therapeutic modality in the setting of complicated prolapsed stoma.

Resumo Introdução A incidência de prolapso de estoma varia de 2 a 22%. Os fatores de risco incluem colostomia, comprimento curto do estoma, obesidade, cirurgias de emergência, e marcação não adequada (ou atémesmo ausente) do sítio pré-operatório para o estoma. Prolapso de estoma complicado e associado a irritação grave de mucosa, alterações isquêmicas, ou sangramento requer intervenção cirúrgica. Objetivo Descrever o uso da técnica de Altemeier para o manejo de prolapso de estoma complicado após fracasso das medidas médicas locais e da redução manual. Métodos Série de casos de três pacientes com histórico de ressecção abdominoperineal de câncer retal e colostomia terminal permanente apresentaram prolapso irredutível do estoma. Com o fracasso das medidas locais e da redução manual, fezse necessária intervenção cirúrgica de emergência usando a técnica de Altemeier modificada. Resultados A técnica de Altemeier modificada é simples e apresenta risco baixo de complicações operatórias e pós-operatórias, além de possibilitar uma recuperação precoce, com menor risco de recorrência durante os 6 primeiros meses após o reparo. Conclusão A técnica de Altemeier modificada pode ser uma modalidade terapêutica válida em casos de prolapso de estoma complicado.

Novel Disulfide-Bridged Bioresponsive Antisense Oligonucleotide Induces Efficient Splice Modulation in Muscle Myotubes in Vitro.

Splice-modulating antisense therapy has shown tremendous potential in therapeutic development in recent years with four FDA-approved antisense drugs since 2016. However, an efficient and nontoxic antisense oligonucleotide (AO) delivery system still remains as a major obstacle in nucleic acid therapeutics field. Vitamin-E (α-tocopherol) is an essential dietary requirement for human body. This fat-soluble compound is one of the most important antioxidants which involves in numerous biological pathways. In this study, for the first time, we explored the scope of using α-tocopherol-conjugated bioresponsive AOs to induce splice modulation in mouse muscle myotubes in vitro. Our results showed that the bioresponsive construct efficiently internalized into the cell nucleus and induced exon 23 skipping in mdx mouse myotubes. Based on our exciting new results, we firmly believe that our findings could potentially benefit toward establishing a delivery approach to advance the field of splice-modulating AO therapy.

Author Correction: Systematic evaluation of 2'-Fluoro modified chimeric antisense oligonucleotide-mediated exon skipping in vitro.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cerebral Venous Thrombosis After a Possible Inadvertent Dural Puncture for Labor Epidural Analgesia.

Pregnancy is a hypercoagulable state that increases the risk of thrombotic complications. A 32-year-old gravida 4 para 3 (G4P3) had a dural puncture during epidural catheter placement for labor analgesia. A positional headache started after delivery and continued for several days. A week after the delivery, she developed non-positional headaches along with seizures. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) lead to the diagnosis of cerebral venous thrombosis (CVT). A factor V Leiden mutation was also found; that was suspected to contribute to the development of CVT along with dural puncture and pregnancy. CVT can present with non-positional headaches a week after the dural puncture.

Systematic evaluation of 2'-Fluoro modified chimeric antisense oligonucleotide-mediated exon skipping in vitro.

Antisense oligonucleotide (AO)-mediated splice modulation has been established as a therapeutic approach for tackling genetic diseases. Recently, Exondys51, a drug that aims to correct splicing defects in the dystrophin gene was approved by the US Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy (DMD). However, Exondys51 has relied on phosphorodiamidate morpholino oligomer (PMO) chemistry which poses challenges in the cost of production and compatibility with conventional oligonucleotide synthesis procedures. One approach to overcome this problem is to construct the AO with alternative nucleic acid chemistries using solid-phase oligonucleotide synthesis via standard phosphoramidite chemistry. 2'-Fluoro (2'-F) is a potent RNA analogue that possesses high RNA binding affinity and resistance to nuclease degradation with good safety profile, and an approved drug Macugen containing 2'-F-modified pyrimidines was approved for the treatment of age-related macular degeneration (AMD). In the present study, we investigated the scope of 2'-F nucleotides to construct mixmer and gapmer exon skipping AOs with either 2'-O-methyl (2'-OMe) or locked nucleic acid (LNA) nucleotides on a phosphorothioate (PS) backbone, and evaluated their efficacy in inducing exon-skipping in mdx mouse myotubes in vitro. Our results showed that all AOs containing 2'-F nucleotides induced efficient exon-23 skipping, with LNA/2'-F chimeras achieving better efficiency than the AOs without LNA modification. In addition, LNA/2'-F chimeric AOs demonstrated higher exonuclease stability and lower cytotoxicity than the 2'-OMe/2'-F chimeras. Overall, our findings certainly expand the scope of constructing 2'-F modified AOs in splice modulation by incorporating 2'-OMe and LNA modifications.

Upper gastrointestinal bleeding in Egyptian patients with cirrhosis: Post-therapeutic outcome and prognostic indicators.

BACKGROUND AND AIM: Upper gastrointestinal bleeding (UGIB) is a serious complication of portal hypertension in cirrhotic patients. The objective of this study is to identify the risk factors for morbidity and mortality occurring after an UGIB attack. METHODS: A total of 1097 UGIB attacks in 690 patients with liver cirrhosis were studied. Their clinical, laboratory, and endoscopic data were reviewed. RESULTS: Mean age 53.2 ± 10.6 (20-90) years, 78% men and the main cause of liver disease was hepatitis C (94.9%). Complications occurred after 467 attacks (42.6%): hepatic encephalopathy 31.4%, spontaneous bacterial peritonitis 18%, renal impairment 13.2%, and re-bleeding in 7.8%, while 199 patients (18.1%) died. Complications followed 78.4% of bleeding from gastric varices, 75% of post-interventional ulcers, 10.8% of peptic ulcers, and 5.9% of telangiectasias. By univariate analysis: packed red blood cells units transfused, transaminases, Child-Pugh (CP), model of end-stage liver disease (MELD), and albumin-bilirubin (ALBI) scores, beside the presence of hepatocellular carcinoma (HCC), previous hemorrhage in the previous 6 months, and the source of bleeding, were associated with occurrence of complications. By multivariate analysis, independent predictors of complications were CP, MELD, and ALBI scores (odds ratio, 95% confidence interval: 5.63, 3.55-8.93; 1.15, 1.11-1.19; and 2.11, 1.4-3.19, respectively) beside the presence of HCC (4.89, 2.48-9.64). Mortality predictors were packed red blood cells units transfused (1.11, 1.01-1.24), CP (5.1, 1.42-18.25) MELD (1.27, 1.21-1.32) scores, and presence of HCC (6.62, 2.93-14.95). CONCLUSION: High CP, MELD, and ALBI scores beside the presence of HCC could predict poor outcome of UGIB. In the absence of these risk factors, early discharge could be considered if the source of bleeding is peptic ulcer or telangiectasia.

Urinary neutrophil gelatinase-associated lipocalin for diagnosis of spontaneous bacterial peritonitis.

Cirrhotic patients with ascites are at high risk of developing spontaneous bacterial peritonitis (SBP). After exclusion of patients with acute kidney injury (AKI) or other infections, urinary neutrophil gelatinase-associated lipocalin (NGAL) levels were compared between two matched groups of Egyptian cirrhotic patients with ascites, mostly secondary to hepatitis C infection (98%). Group 1 had SBP (n = 41) and group 2 did not (n = 45). By univariate analysis, urinary-NGAL, high total bilirubin, serum creatinine, international normalised ratio and the Model of End-Stage Liver Disease (MELD) score and low platelet count were all significantly correlated with the presence of SBP, but only urinary-NGAL could independently predict development of SBP (P = 0.001). Urinary-NGAL at a cut-off value of 1225 pg/mL, showed a sensitivity of 95% and a specificity of 76%, and is therefore a most useful tool.

Antisense Oligonucleotides Targeting Angiogenic Factors as Potential Cancer Therapeutics.

Cancer is one of the leading causes of death worldwide, and conventional cancer therapies such as surgery, chemotherapy, and radiotherapy do not address the underlying molecular pathologies, leading to inadequate treatment and tumor recurrence. Angiogenic factors, such as EGF, PDGF, bFGF, TGF-ß, TGF-α, VEGF, endoglin, and angiopoietins, play important roles in regulating tumor development and metastasis, and they serve as potential targets for developing cancer therapeutics. Nucleic acid-based therapeutic strategies have received significant attention in the last two decades, and antisense oligonucleotide-mediated intervention is a prominent therapeutic approach for targeted manipulation of gene expression. Clinical benefits of antisense oligonucleotides have been recognized by the U.S. Food and Drug Administration, with full or conditional approval of Vitravene, Kynamro, Exondys51, and Spinraza. Herein we review the scope of antisense oligonucleotides that target angiogenic factors toward tackling solid cancers.

Effects of acute rejection vs new-onset diabetes after transplant on transplant outcomes in pediatric kidney recipients: analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database.

Improving long-term transplant and patient survival is still an ongoing challenge in kidney transplant medicine. Our objective was to identify the subsequent risks of new-onset diabetes after transplant (NODAT) and acute rejection (AR) in the first year post-transplant in predicting mortality and transplant failure. A total of 4687 patients without preexisting diabetes (age 2-20 years, 2004-2010) surviving with a functioning transplant for longer than 1 year with at least one follow-up report were identified from the OPTN/UNOS database as of September 2014. Study population was stratified into four mutually exclusive groups: Group 1, patients with a history of AR; Group 2, NODAT+; Group 3, NODAT+ AR+; and Group 4, the reference group (neither). Multivariate regression was used to analyze the relative risks for the outcomes of transplant failure and mortality. The median follow-up time was 1827 days after 1 year post-transplant. AR was associated with an increased risk of adjusted graft and death-censored graft failure (HR 2.87, CI 2.48-3.33, P < .001 and HR 2.11, CI 1.81-2.47, P < .001), respectively. NODAT and AR were identified in 3.5% and 14.5% of all study patients, respectively. AR in the first year post-transplant was a major risk factor for overall and death-censored graft failure, but not mortality. However, NODAT was not a risk factor on graft survival or mortality.

Anti-parallel triplexes: Synthesis of 8-aza-7-deazaadenine nucleosides with a 3-aminopropynyl side-chain and its corresponding LNA analog.

The phosphoramidites of DNA monomers of 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine (Y) and 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine LNA (Z) are synthesized, and the thermal stability at pH 7.2 and 8.2 of anti-parallel triplexes modified with these two monomers is determined. When, the anti-parallel TFO strand was modified with Y with one or two insertions at the end of the TFO strand, the thermal stability was increased 1.2°C and 3°C at pH 7.2, respectively, whereas one insertion in the middle of the TFO strand decreased the thermal stability 1.4°C compared to the wild type oligonucleotide. In order to be sure that the 3-aminopropyn-1-yl chain was contributing to the stability of the triplex, the nucleobase X without the aminopropynyl group was inserted in the same positions. In all cases the thermal stability was lower than the corresponding oligonucleotides carrying the 3-aminopropyn-1-yl chain, especially at the end of the TFO strand. On the other hand, the thermal stability of the anti-parallel triplex was dramatically decreased when the TFO strand was modified with the LNA monomer analog Z in the middle of the TFO strand (ΔTm=-9.1°C). Also the thermal stability decreased about 6.1°C when the TFO strand was modified with Z and the Watson-Crick strand with adenine-LNA (A(L)). The molecular modeling results showed that, in case of nucleobases Y and Z a hydrogen bond (1.69 and 1.72Ǻ, respectively) was formed between the protonated 3-aminopropyn-1-yl chain and one of the phosphate groups in Watson-Crick strand. Also, it was shown that the nucleobase Y made a good stacking and binding with the other nucleobases in the TFO and Watson-Crick duplex, respectively. In contrast, the nucleobase Z with LNA moiety was forced to twist out of plane of Watson-Crick base pair which is weakening the stacking interactions with the TFO nucleobases and the binding with the duplex part.

Thermal stability of G-rich anti-parallel DNA triplexes upon insertion of LNA and α-L-LNA.

G-rich anti-parallel DNA triplexes were modified with LNA or α-L-LNA in their Watson-Crick and TFO strands. The triplexes were formed by targeting a pyrimidine strand to a putative hairpin formed by Hoogsteen base pairing in order to use the UV melting method to evaluate the stability of the triplexes. Their thermal stability was reduced when the TFO strand was modified with LNA or α-L-LNA. The same trend was observed when the TFO strand and the purine Watson-Crick strand both were modified with LNA. When all triad components were modified with α-L-LNA and LNA in the middle of the triplex, the thermal melting was increased. When the pyrimidine sequence was modified with a single insertion of LNA or α-L-LNA the ΔTm increased. Moreover, increasing the number of α-L-LNA in the pyrimidine target sequence to six insertions, leads to a high increase in the thermal stability. The conformational S-type structure of α-L-LNA in anti-parallel triplexes is preferable for triplex stability.

Prediction of cardiac complications after liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) stresses the cardiovascular system, and cardiac complications after OLT are common. METHODS: Hundred ninety-seven patients (>or=40 years) who had OLT from 2002 to 2007 were reviewed to identify predictors of cardiac complications within 6 months after transplantation. RESULTS: Median age was 56 years (40-75 years); 69% men. Reasons for OLT were hepatitis C virus (HCV) 45.5%, alcohol 22%, hepatocellular carcinoma (HCC) 8%, primary biliary cirrhosis 10%, and others 14.5%. Eighty-two patients suffered one or more cardiac complications within 6 months after OLT (pulmonary edema=61 [overt heart failure=7], arrhythmia=13, pulmonary hypertension=7, pericardial effusion=2, and right atrial thrombus=1). Cardiac causes were the leading cause of death (n=5; 23.8% of all mortality). By multivariate analysis, after adjusting for age and sex, independent predictors were adverse intraoperative cardiovascular events (adjusted odds ratio; 95% confidence interval: 5.89, 1.82-19.14), history of cardiac disease (2.42, 0.89-6.6), and i-MELD (integrated model for end-stage liver disease) score (1.08, 1.02-1.14), whereas adverse intraoperative cardiovascular events (5.73, 1.96-16.78) and i-MELD (1.07, 1.01-1.13) predicted pulmonary edema. None of the following variables predicted complications: age, sex, OLT indication, body mass index, blood pressure, alcohol and smoking history, pre-OLT investigations (chest X-ray, electrocardiogram, echocardiography, coronary angiography, pulmonary arterial pressure, and 2-methoxy isobutyl isonitrile scan), immunosuppressive treatment, or intraoperative variables (transfusion amount, cadaveric vs. living graft or cold ischemia and rewarming times). CONCLUSIONS: Cardiac complications after OLT are common and were the leading cause of death after surgery. Adverse intraoperative cardiovascular events, previous cardiac disease, and advanced liver disease as quantified by i-MELD score predicted postoperative cardiac complications.

Cirrhotic cardiomyopathy.

Liver cirrhosis is associated with several cardiovascular abnormalities. Despite an increased baseline cardiac output, cirrhotic patients have a suboptimal ventricular response to stress. This phenomenon is called cirrhotic cardiomyopathy. The pathogenesis of this syndrome is multifactorial and includes diminished beta-adrenergic receptor signal transduction, cardiomyocyte cellular plasma membrane dysfunction, and increased activity or levels of cardiodepressant substances such as cytokines, endogenous cannabinoids, and nitric oxide. Although cirrhotic cardiomyopathy is usually clinically mild or silent, overt heart failure can be precipitated by stresses such as liver transplantation or transjugular intrahepatic portosystemic shunt insertion. Moreover, cirrhotic cardiomyopathy may play a role in the pathogenesis of hepatorenal syndrome. Treatment of this condition is mainly supportive. Orthotopic liver transplantation appears to improve or normalize the condition, generally after a period of several months.

Cirrhotic cardiomyopathy.

Cirrhotic cardiomyopathy is the term used to describe a constellation of features indicative of abnormal heart structure and function in patients with cirrhosis. These include systolic and diastolic dysfunction, electrophysiological changes, and macroscopic and microscopic structural changes. The prevalence of cirrhotic cardiomyopathy remains unknown at present, mostly because the disease is generally latent and shows itself when the patient is subjected to stress such as exercise, drugs, hemorrhage and surgery. The main clinical features of cirrhotic cardiomyopathy include baseline increased cardiac output, attenuated systolic contraction or diastolic relaxation in response to physiologic, pharmacologic and surgical stress, and electrical conductance abnormalities (prolonged QT interval). In the majority of cases, diastolic dysfunction precedes systolic dysfunction, which tends to manifest only under conditions of stress. Generally, cirrhotic cardiomyopathy with overt severe heart failure is rare. Major stresses on the cardiovascular system such as liver transplantation, infections and insertion of transjugular intrahepatic portosystemic stent-shunts (TIPS) can unmask the presence of cirrhotic cardiomyopathy and thereby convert latent to overt heart failure. Cirrhotic cardiomyopathy may also contribute to the pathogenesis of hepatorenal syndrome. Pathogenic mechanisms of cirrhotic cardiomyopathy are multiple and include abnormal membrane biophysical characteristics, impaired beta-adrenergic receptor signal transduction and increased activity of negative-inotropic pathways mediated by cGMP. Diagnosis and differential diagnosis require a careful assessment of patient history probing for excessive alcohol, physical examination for signs of hypertension such as retinal vascular changes, and appropriate diagnostic tests such as exercise stress electrocardiography, nuclear heart scans and coronary angiography. Current management recommendations include empirical, nonspecific and mainly supportive measures. The exact prognosis remains unclear. The extent of cirrhotic cardiomyopathy generally correlates to the degree of liver insufficiency. Reversibility is possible (either pharmacological or after liver transplantation), but further studies are needed.

Transverse colon diverticulitis simulating inguinal hernia strangulation: a first report.

BACKGROUND: Strangulation is the most serious complication of inguinal hernia. Diverticulitis, a common condition, is usually localized in the left colon. The association of complicated inguinal hernia and diverticulitis is rare. METHODS: We report the case of a 73-year-old male patient who presented with a suspicion of strangulated inguinal hernia. RESULTS: CT and operative findings showed transverse colon diverticulitis lodged in an incarcerated inguinal hernia without signs of strangulation. Surgical hernia repair was undertaken while the treatment of diverticulitis was conservative. Follow-up was uneventful. CONCLUSION: This is a first report of documented transverse colon diverticulitis simulating inguinal hernia strangulation.

Pilot detection study of alpha(1) antitrypsin deficiency in a targeted population.

Screenings for the genetic disorder alpha(1) antitrypsin deficiency (AAT Deficiency) have been one of two models: large screenings of general populations and small targeted detection programs in high-risk groups. The most appropriate screening and detection methodologies in terms of target populations, subject participation and yield of positive tests, however, have not been well defined. The major objective of this pilot study was to evaluate the effectiveness in terms of participation of two different AAT Deficiency detection programs using a self-administered fingerstick blood test. Individuals ages 30-60 under the care of a pulmonary physician and with a diagnosis of emphysema, COPD, chronic bronchitis, or bronchiectasis were the targeted population. Participants were offered AAT Deficiency testing in the pulmonary physician's office compared with testing offered through mail. Participation (i.e., frequency of subject participation in the detection program) of two different AAT Deficiency detection programs. Non-participation was due to fear of self-administered testing and research studies; women were more likely to participate than men. Eligible subjects were significantly more likely to participate when offered testing by their pulmonary physician in-office (83%) than mail-only (42%) (P < 0.02). Although self-administered genetic testing is available, highest participation in AAT Deficiency detection program was found when offered directly by the physician. This finding may have implications for screening and detection of other genetic diseases. Future studies need to evaluate the yield (i.e., frequency of positive tests) of these detection methodologies in highly targeted populations.