High rate of incisional hernia observed after mass closure of burst abdomen.

PURPOSE: This study investigated the long-term development of incisional hernia after implementation of a standardized surgical treatment strategy for burst abdomen in abdominal midline incisions with a continuous mass closure technique. METHODS: The study was a single-center, observational study evaluating all patients treated for burst abdomen between June 2014 and April 2019 with a long-term follow-up in October 2020. In June 2014, a standardized surgical treatment for burst abdomen involving a monofilament, slowly absorbable suture in a continuous mass-closure stitch with large bites of 3 cm and small steps of 5 mm was introduced. The occurrence of incisional hernia was investigated and defined as a radiological-, clinical-, or intraoperative finding of a hernia in the abdominal midline incision at follow-up. RESULTS: Ninety-four patients suffered from burst abdomen during the study period. Eighty patients were eligible for follow-up. The index surgery prior to burst abdomen was an emergency laparotomy in 78% (62/80) of the patients. Nineteen patients died within the first 30 postoperative days and 61 patients were available for further analysis. The long-term incisional hernia rate was 33% (20/61) with a median follow-up of 17 months (min 4, max 67 months). CONCLUSION: Standardized surgery for burst abdomen with a mass-closure technique using slow absorbable running suture results in high rates of long-term incisional hernias, comparable to the hernia rates reported in the literature among this group of patients.

Reduced rate of incisional hernia after standardized fascial closure in emergency laparotomy.

PURPOSE: Emergency laparotomy is a high-risk procedure, and incisional hernia is a common complication. This study aimed to investigate whether a standardized fascial closure technique, using slowly absorbable monofilament suture in a ratio of at least 1:4, could reduce the long-term occurrence of incisional hernia after emergency laparotomy. METHODS: The single-center study was conducted as a questionnaire study including all patients who had an emergency laparotomy at Copenhagen University Hospital Herlev from May 2009 to May 2013 and June 2014 to November 2015. The historic cohort was used as a control. In the historic cohort of 2009-2013, different fascial closing techniques were used according to the preference of the individual surgeon. On June 1, 2014, we introduced a standardized method of fascial closure. RESULTS: A total of 465 patients met our inclusion criteria. The response rate was 77%. In all, 104 patients developed an incisional hernia: 77(27.0%) in the historic group and 27(15.0%) in the 2014-2015 group (p = 0.02). At long-term follow-up, 104 patients had undergone elective incisional herniotomy or had an incisional hernia confirmed by a medical doctor. The rate of incisional hernia was reduced from 27.0 to 15.0% (p = 0.02) comparing years 2009-2013 with 2014-2015. CONCLUSIONS: This study suggests that development of incisional hernia may be reduced significantly if a standardized technique is applied using slowly absorbable monofilament suture in a ratio of at least 1:4 in emergency laparotomies.

The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon.

Toll-like receptor 9 (TLR9) agonists are being developed for treatment of colorectal and other cancers, yet the impact of these drugs on human intestines remains unknown. This, together with the fact that there are additional potential indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703 (60 mg s.c.) twice weekly for 4 weeks in a single-arm, phase 1b/2a study. Within sigmoid mucosa, global transcriptomic analyses revealed 248 modulated genes (false discovery rate<0.05) including many type I interferon (IFN)-stimulated genes. MGN1703 increased the frequencies of cells exhibiting MX1 (P=0.001) and ISG15 (P=0.014) protein expression. No changes were observed in neutrophil infiltration (myeloperoxidase; P=0.97). No systematic effect on fecal microbiota structure was observed (analysis of similarity Global R=-0.105; P=0.929). TLR9 expression at baseline was inversely proportional to the change in integrated HIV DNA during MGN1703 treatment (P=0.020). In conclusion, MGN1703 induced a potent type I IFN response, without a concomitant general inflammatory response, in the intestines.

Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): Immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs.

OBJECTIVES: The REDUC clinical study Part B investigated Vacc-4x/rhuGM-CSF therapeutic vaccination prior to HIV latency reversal using romidepsin. The main finding was a statistically significant reduction from baseline in viral reservoir measurements. Here we evaluated HIV-specific functional T-cell responses following Vacc-4x/rhuGM-CSF immunotherapy in relation to virological outcomes on the HIV reservoir. METHODS: This study, conducted in Aarhus, Denmark, enrolled participants (n = 20) with CD4>500 cells/mm3 on cART. Six Vacc-4x (1.2 mg) intradermal immunizations using rhuGM-CSF (60 µg) as adjuvant were followed by 3 weekly intravenous infusions of romidepsin (5 mg/m2). Immune responses were determined by IFN-γ ELISpot, T-cell proliferation to p24 15-mer peptides covering the Vacc-4x region, intracellular cytokine staining (ICS) to the entire HIVGag and viral inhibition. RESULTS: The frequency of participants with CD8+ T-cell proliferation assay positivity was 8/16 (50%) at baseline, 11/15 (73%) post-vaccination, 6/14 (43%) during romidepsin, and 9/15 (60%)post-romidepsin. Participants with CD8+ T-cell proliferation assay positivity post-vaccination showed reductions in total HIV DNA post-vaccination (p = 0.006; q = 0.183), post-latency reversal (p = 0.005; q = 0.183), and CA-RNA reductions post-vaccination (p = 0.015; q = 0.254). Participants (40%) were defined as proliferation 'Responders' having ≥2-fold increase in assay positivity post-baseline. Robust ELISpot baseline responses were found in 87.5% participants. No significant changes were observed in the proportion of polyfunctional CD8+ T-cells to HIVGag by ICS. There was a trend towards increased viral inhibition from baseline to post-vaccination (p = 0.08). CONCLUSIONS: In this 'shock and kill' approach supported by therapeutic vaccination, CD8+ T-cell proliferation represents a valuable means to monitor functional immune responses as part of the path towards functional HIV cure.

Complications after emergency laparotomy beyond the immediate postoperative period - a retrospective, observational cohort study of 1139 patients.

Mortality and morbidity occur commonly following emergency laparotomy, and incur a considerable clinical and financial healthcare burden. Limited data have been published describing the postoperative course and temporal pattern of complications after emergency laparotomy. We undertook a retrospective, observational, multicentre study of complications in 1139 patients after emergency laparotomy. A major complication occurred in 537/1139 (47%) of all patients within 30 days of surgery. Unadjusted 30-day mortality was 20.2% and 1-year mortality was 34%. One hundred and thirty-seven of 230 (60%) deaths occurred between 72 h and 30 days after surgery; all of these patients had complications, indicating that there is a prolonged period with a high frequency of complications and mortality after emergency laparotomy. We conclude that peri-operative, enhanced recovery care bundles for preventing complications should extend their focus on continuous complication detection and rescue beyond the first few postoperative days.

30-Day, 90-day and 1-year mortality after emergency colonic surgery.

PURPOSE: Emergency surgery is an independent risk factor in colonic surgery resulting in high 30-day mortality. The primary aim of this study was to report 30-day, 90-day and 1-year mortality rates after emergency colonic surgery, and to report factors associated with 30-day, 90-day and 1-year mortality. Second, the aim was to report 30-day postoperative complications and their relation to in-hospital mortality. METHODS: All patients undergoing acute colonic surgery in the period from May 2009 to April 2013 at Copenhagen University Hospital Herlev, Denmark, were identified. Perioperative data was collected from medical journals. RESULTS: 30-day, 90-day and 1-year mortality was 21, 30 and 41%, respectively. Age >70 years, Performance status ≥3 and resection with stoma were independent factors associated with 30-day mortality. Age >70 years, Performance status ≥3, resection with stoma and malignant disease were independent risk factors associated with 90-day mortality. Age >70 years, Performance status ≥3, resection with stoma and malignant disease were independent factors associated with 1-year mortality. Overall, 30-day complication rate was 63%, with cardiopulmonary complications leading to most postoperative deaths. CONCLUSION: Mortality and complication rates after emergency colonic surgery are high and associated with patient related risk factors that cannot be modified, but also treatment related outcomes that are modifiable. An increased focus on medical and other preventive measures should be explored in the future.

Innate DNA sensing is impaired in HIV patients and IFI16 expression correlates with chronic immune activation.

The innate immune system has been recognized to play a role in the pathogenesis of HIV infection, both by stimulating protective activities and through a contribution to chronic immune activation, the development of immunodeficiency and progression to AIDS. A role for DNA sensors in HIV recognition has been suggested recently, and the aim of the present study was to describe the influence of HIV infection on expression and function of intracellular DNA sensing. Here we demonstrate impaired expression of interferon-stimulated genes in responses to DNA in peripheral blood monuclear cells from HIV-positive individuals, irrespective of whether patients receive anti-retroviral treatment. Furthermore, we show that expression levels of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic guanosine monophosphate-adenosine monophosphate synthase were increased in treatment-naive patients, and for IFI16 expression was correlated with high viral load and low CD4 cell count. Finally, our data demonstrate a correlation between IFI16 and CD38 expression, a marker of immune activation, in CD4(+) central and effector memory T cells, which may indicate that IFI16-mediated DNA sensing and signalling contributes to chronic immune activation. Altogether, the present study demonstrates abnormal expression and function of cytosolic DNA sensors in HIV patients, which may have implications for control of opportunistic infections, chronic immune activation and T cell death.

Dynamics of 103K/N and 184M/V HIV-1 drug resistant populations: relative comparison in plasma virus RNA versus CD45RO+T cell proviral DNA.

BACKGROUND: Viral populations defined by 103K/N and 184M/V as linked or single mutations in the HIV-1 reverse transcriptase gene were investigated in plasma samples and compared with previous findings in the CD45RO(+)T cell compartment. OBJECTIVE: To develop an ARMS assay for plasma virions and to investigate the expression of resistance mutations (103N and 184V) and dynamic interactions between proviral DNA and plasma virions. STUDY DESIGN: A clinical cross-sectional study, including 11 patients on lamivudine efavirenz and/or nevirapine therapy. The viral populations were determined by an assay based on real-time PCR and amplification refractory mutation system (ARMS). RESULTS: The 103N and 184V mutations were not detected in patients with stable low viremia. Patients previously exposed to mono or dual therapy often carried minor viral populations of either one or both mutations in plasma. The viral population with linked mutations (103N and 184V) was detected in two patients after more than 2 years of non-NNRTI HAART. CONCLUSION: The ARMS assay is useful for detecting viral quasi-species containing efavirenz and lamivudine resistant mutations in plasma virions and in proviral DNA. Data suggest an unequal distribution of linked-mutation populations in plasma and CD45RO(+)T cells. Furthermore, the linked 103N-184V mutation may be more fit than the single 184V mutation and this linked population emerges rapidly under inadequate drug pressure.

Trainability of the pelvic floor. A prospective study during pregnancy and after delivery.

The contractibility and trainability of the pelvic floor were investigated during pregnancy and after vaginal delivery in 86 healthy primiparae. One group (TG) (n = 38) was instructed in training the pelvic floor from the 33rd week of pregnancy, whereas the other group (non-TG) (n = 39) was not. Both groups were measured by perineometry five times between 33rd-39th week of pregnancy and approximately 8 weeks after delivery. Half of the women were also measured 8 months post partum. At the beginning of the study both groups showed the same strength of the pelvic floor. 8 weeks and 8 months after delivery the TG were significantly (p less than 0.05) better able to contract the pelvic floor compared with the non-TG. 8 months post partum, the TG had regained the initial values of pelvic floor contraction as from 33rd week of pregnancy, whereas the non-TG had not. During pregnancy there was a better ability to contract the pelvic floor in the TG vis-à-vis the non-TG, though not significantly so. No difference in the course of delivery was observed, and the frequency of complications was the same in the two groups.