Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.

Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal positron emission tomography and computed tomography imaging, single-cell RNA sequencing, and measures of bacterial clearance. Bacterial persistence occurred in granulomas enriched for mast, endothelial, fibroblast, and plasma cells, signaling amongst themselves via type 2 immunity and wound-healing pathways. Granulomas that drove bacterial control were characterized by cellular ecosystems enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-inflammatory signaling networks involving diverse cell populations. Granulomas that arose later in infection displayed functional characteristics of restrictive granulomas and were more capable of killing Mtb. Our results define the complex multicellular ecosystems underlying (lack of) granuloma resolution and highlight host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB.

Suicide after colorectal cancer-a national population-based study.

AIM: A cancer diagnosis is often associated with physical as well as emotional distress. Previous studies indicate a higher risk for suicide in patients diagnosed with cancer. The aim of this study was to investigate the prevalence of death by suicide in a national cohort of patients with newly diagnosed colorectal cancer compared with a matched control group to determine if patients with colorectal cancer had an increased incidence of death by suicide. METHOD: This national Swedish cohort was retrieved from the register-based research database CRCBaSe, which includes all patients diagnosed with colorectal cancer between 1997-2006 (rectal) and 2008-2016 (colon) and six controls for each patient matched by age, sex, and county. Cause specific mortality due to suicide was modelled using Cox proportional hazards model and adjusted for known risk factors. RESULTS: The main analysis included patients operated for colorectal cancer, 55 578 patients compared with 307 888 controls. The first year after diagnosis the hazard ratio (HR) for suicide among patients operated for colorectal cancer was 1.86 (CI: 1.18-2.95) compared to controls. Suicide was more common among men than women (HR 2.08; 1.26-3.42 vs. 1.09; 0.32-3.75). A subgroup analysis of the 9198 patients who did not undergo surgery after diagnoses found a seven-fold increase of suicide (HR 7.03; 3.10-15.91). CONCLUSION: Suicide after surgery for colorectal cancer was almost twice as high as in the control group, mainly driven by excess mortality among men. Although the cases were few in the subgroup of nonoperated patients, the considerably higher risk of suicide indicates that more resources might be needed in this group. Evaluation of risk factors for suicide among patients with colorectal cancer should be performed for early identification of individuals at risk.

Clinical decision rules for appendicitis are not used by surgeons in training: A survey.

BACKGROUNDS: We aimed to investigate surgeons in training knowledge of clinical decision rules (CDR) for diagnosing appendicitis and their attitudes toward implementing them. METHODS: We included surgeons in training practicing in East Denmark who independently could decide to perform a diagnostic laparoscopy for suspected appendicitis. The survey was developed in Research Electronic Data Capture and face-validated before use. It consisted of three parts: (1) the characteristics of the surgeons, (2) their diagnostic approach, and (3) their knowledge and attitude toward introducing CDR in the clinic. Data were collected in January 2023. RESULTS: We achieved 83 (90%) responses, and 52% of surgeons in training believed that appendicitis was difficult to diagnose. Their diagnostic approach mostly included symptoms and physical examinations for abdominal pain, and C-reactive protein. A total of 48% knew of at least one clinical decision rule, and 72% had never used a clinical decision rule. Regarding the necessity of CDR in clinical practice, surgeons in training options were divided into thirds: not needed, neither needed nor not needed, and needed. Surgeons in training indicated that CDR needed to be validated and easily applied before they would implement them. CONCLUSION: Approximately 3/4 of surgeons in training had never utilized a clinical decision rule to diagnose appendicitis, and only half knew of their existence. The symptoms and findings incorporated in most CDR aligned with their diagnostic approach. They were conflicted if CDR needed to be implemented in clinical practice.

Transabdominal pre-peritoneal (TAPP) versus totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair.

BACKGROUND: An inguinal hernia occurs when part of the intestine protrudes through the abdominal muscles. In adults, this common condition is much more likely in men than in women. Inguinal hernia can be monitored by 'watchful waiting', but if symptoms persist or worsen, surgery is usually required, which can be open or laparoscopic. Laparoscopic (keyhole) repair of inguinal hernias in adults is generally performed using either the transabdominal preperitoneal (TAPP) or the totally extraperitoneal (TEP) method. Both methods include the use of mesh placed in front of the peritoneal lining of the abdominal wall, but for the TAPP technique, the abdominal cavity needs to be entered to place the mesh, and for the TEP technique, the whole procedure is done on the outside of the peritoneal lining of the abdominall wall. Whether one method is superior to the other has not been established, and there is debate about their relative benefits and harms. An advantage of TEP is its avoidance of the abdominal cavity; the downside is that it requires a steeper learning curve for clinicians. TAPP is considered simpler and makes it possible to inspect the contralateral side, but TAPP may have a higher risk of visceral injury compared to TEP. This is an update of a Cochrane review first published in 2005. OBJECTIVES: To compare the benefits and harms of laparoscopic TAPP technique versus laparoscopic TEP technique for inguinal hernia repair in adults. SEARCH METHODS: On 25 October 2022, the authors searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); and Ovid Embase, for published randomised controlled trials. To identify studies in progress, we searched ClinicalTrials.gov and the WHO International Clinical Trial Registry Platform (ICTRP). SELECTION CRITERIA: All prospective randomised, quasi-randomised, and cluster-randomised trials that compared the laparoscopic TAPP technique with the laparoscopic TEP technique for inguinal hernia repair in adults were eligible for inclusion. We included studies that involved a mix of different types of groin hernia if we could extract data for the inguinal hernias. Studies may have also included a group of participants receiving hernia repair by open surgery, but these groups were not included in our review. DATA COLLECTION AND ANALYSIS: Both review authors independently evaluated trial eligibility, extracted data from included studies, and assessed the risk of bias in the included studies. The review's primary outcomes were serious adverse events, chronic pain (persisting for at least six months after surgery), and hernia recurrence. We also assessed a variety of secondary outcomes at perioperative, early postoperative, and late postoperative time points. We performed statistical analyses using the random-effects model, and expressed the results as odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with their respective 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for key outcomes as high, moderate, low or very low. MAIN RESULTS: We included 23 studies in this review update, which randomised 1156 people to TAPP and 1110 people to TEP, all requiring repair of inguinal hernias. Study sample sizes varied from 40 to 316 participants. The vast majority of study participants were male. We judged most studies to be at 'high' or 'unclear' risk of bias. Our judgements of the certainty of the evidence were low or very low for all outcomes we assessed. There may be little to no difference between TAPP and TEP laparoscopic techniques for serious adverse events (0.4% versus 0.7%; OR 0.58, 95% CI 0.15 to 2.32, P = 0.45, I2 = 0%; 19 studies, 1735 participants; low certainty of evidence); and hernia recurrence (1.2% versus 1.1%; OR 1.14, 95% CI 0.49 to 2.62, P = 0.97, I2 = 0%; 17 studies, 1712 participants; low certainty of evidence). The evidence is very uncertain about the effects of TAPP versus TEP techniques on chronic pain (OR 0.62, 95% CI 0.20 to 1.97, P = 0.68, I2 = 0%; 6 studies, 860 participants; very low certainty of evidence). In terms of secondary outcomes, the evidence is very uncertain for TAPP versus TEP techniques for perioperative visceral and vascular injury (15 studies, 1523 participants; very low certainty of evidence), and for haematoma or seroma during the early (≤ 30 days) postoperative phase (OR 0.86, 95% CI 0.54 to 1.37, P = 0.3861, I2 = 0%; 15 studies, 1423 participants; very low certainty of evidence). TEP technique may carry a higher risk of conversion to another hernia repair method (either TAPP technique or open surgery) when compared to TAPP (2.5% versus 0.7%; OR 0.28, 95% CI 0.09 to 0.84, P = 0.02, I2 = 0%; 13 studies, 1178 participants; low certainty of evidence). Only two studies (474 participants) reported quality of life in the late (> 30 days) postoperative phase; overall, there was an improvement in quality of life from the pre- to post-operative assessment, but the evidence suggests little to no difference between the techniques (low certainty of evidence). AUTHORS' CONCLUSIONS: This review update found that there may be little to no difference between the TAPP and TEP techniques for serious adverse events, hernia recurrence, or chronic pain (low- to very-low-certainty evidence). Decisions about which method to use will most likely reflect surgeon and patient preference until high-certainty evidence becomes available. There may be a higher risk of needing to convert from TEP to TAPP or open surgery when compared to the risk of needing to convert from TAPP to open surgery (low-certainty evidence). If surgeons opt for TEP as their standard laparoscopic method, they could consider having a strategy for how to handle the potential need for conversion. This might include proficiency in the TAPP approach or having informed the patient about the risk of conversion to open surgery. For surgeons or surgical departments, the choice of a laparoscopic technique should involve shared decision-making with patients and their families or carers. Future research could focus on patient-reported outcomes, such as quality of life.

Coatings for Permanent Meshes Used to Enhance Healing in Abdominal Hernia Repair: A Scoping Review.

INTRODUCTION: Hernia meshes are used to reduce recurrence and pain rates, but the rates are still high. This could be improved with coatings of the mesh. This scoping review aimed to provide an overview of mesh coatings used to promote healing in abdominal hernia repair and to report beneficial and unbeneficial effects. METHODS: We included human and animal studies with abdominal hernias that were repaired with non-commercially coated meshes. We searched Pubmed, Embase, Cochrane Central, LILACS, and CNKI without language constraints. RESULTS: Of 2933 identified studies, 58 were included: six studies had a total of 408 humans and 52 studies had 2679 animals. The median follow-up was 12 months (range 1-156), and 95% of the hernias were incisional. There were 44 different coatings which included platelet-rich plasma, mesenchymal stem cells, growth factors, vitamin E, collagen-derived products, various polysaccharides, silk proteins, chitosan, gentamycin, doxycycline, nitrofurantoin, titanium, and diamond-like carbon. Mesenchymal stem cells and platelet-rich plasma were the most researched. Mesenchymal stem cells notably reduced inflammation and foreign body reactions but did not impact other healing metrics. In contrast, platelet-rich plasma positively influenced tissue ingrowth, collagen deposition, and neovascularization and had varying effects on inflammation and foreign body reactions. CONCLUSION: We identified 44 different mesh coatings and they showed varying results. Mesenchymal stem cells and platelet-rich plasma were the most studied, with the latter showing considerable promise in improving biomechanical properties in hernia repair. Further investigations are needed to ascertain their definitive use in humans.

The symptom burden and the assessment of palliative symptoms in patients with metastatic upper gastrointestinal cancer: A qualitative interview study.

OBJECTIVES: Patients with metastatic upper gastrointestinal (GI) cancer may experience a large physical symptom burden. However, less is known about existential, social, and psychological symptoms. To provide the patient with palliative care, quality-of-life questionnaires are used for structured needs assessment. These are sporadically implemented, and there seems to be uncertainty to the efficiency of current practice. The aim of study was to explore the experienced assessment-process and treatment of palliative symptoms, as well as the experienced symptom burden, in patients with metastatic upper GI cancer. METHODS: Qualitative, semi-structured interviews were conducted in 10 patients with metastatic upper GI cancer. Data were analyzed using content analysis. RESULTS: The patients did not expect treatment for all physical symptoms. Existential symptoms revolved around death and dying, social issues were mainly related to family, and psychological issues were based in the continuous dealing with serious illness. Existential, social, and psychological symptoms were mostly not considered part of the expected care when admitted to hospital. Patients had only vague recollections of their experiences with structured needs assessment, and the process had been inconsequential in the treatment of symptoms. SIGNIFICANCE OF RESULTS: Patients with upper GI cancer experience symptoms related to all 4 areas of palliative care being physical, existential, social, and psychological, but these are differentiated in the way patients perceive their origins and treatability. Structured needs assessment was not routinely carried out, and in cases where this had been done, no follow-up was effectuated. This calls for increased focus and proper implementation for the process to be relevant in the treatment of palliative symptoms.

Reoperation for Recurrence is Affected by Type of Mesh in Laparoscopic Ventral Hernia Repair: A Nationwide Cohort Study.

OBJECTIVE: To compare the reoperation rate for recurrence between different mesh types in laparoscopic ventral hernia repair. SUMMARY OF BACKGROUND DATA: Ventral hernia repair has improved over the last decades. Nevertheless, recurrence rates are still high, and one type of mesh was recently found to increase it even more. METHODS: A nationwide cohort study based on prospectively collected data from the Danish Ventral Hernia Database. We included adult patients that had undergone a laparoscopic ventral hernia repair for either an incisional or a primary hernia. The primary and incisional hernias were analyzed in separate cohorts. The mesh-group with the lowest reoperation for recurrence curve was used as the reference. The outcome was reoperation for recurrence. RESULTS: Study population comprised 2874 patients with primary hernias and 2726 with incisional hernias. For primary hernias, Physiomesh [HR = 3.45 (2.16-5.51)] and Proceed Surgical Mesh [HR = 2.53 (1.35-4.75)] had a significantly higher risk of reoperation for recurrence than DynaMesh-IPOM. For incisional hernias, Physiomesh [HR = 3.90 (1.80-8.46), Ventralex Hernia Patch (HR = 2.99 (1.13-7.93), Parietex Composite (incl. Optimized) (HR = 2.55 (1.17-5.55), and Proceed Surgical Mesh (HR = 2.63 (1.11-6.20)] all had a significantly higher risk of reoperation for recurrence than Ventralight ST Mesh. CONCLUSION: For primary hernias, Physiomesh and Proceed Surgical Mesh had a significantly higher risk of reoperation for recurrence compared with DynaMesh-IPOM. For incisional hernias, the risk was significantly higher for Physiomesh, Parietex Composite, Ventralex Hernia Patch, and Proceed Surgical Mesh compared with Ventralight ST Mesh. This indicates that type of mesh may be associated with outcomes, and mesh choice could therefore depend on hernia type.

The Alvarado Score Is the Most Impactful Diagnostic Tool for Appendicitis: A Bibliometric Analysis.

INTRODUCTION: The objective of this bibliometric analysis was to investigate the citation pattern of studies that have developed a diagnostic tool to diagnose appendicitis. METHODS: We investigated characteristics of citations, publication frequency, evolution of citations, and fluctuation of previously highly cited studies. We analyzed which studies had been cited in the method section and identified impactful studies in this research field by a network visualization. We analyzed the differences in citations between diagnostic tools requiring a doctor to be present against the diagnostic tools not requiring doctors to be present, English language studies against non-English studies, and identified diagnostic tools targeting children. RESULTS: There was an upward trend in publications in this research field, and between 1999-2021 the Alvarado score has been cited the most. In general, there was a high fluctuation, and 40 studies had been cited in the methods sections. There were significant differences in studies regarding diagnostic tools written in English compared to non-English studies, with more citations in the English-language studies. Furthermore, 22 studies had children as the target population. CONCLUSIONS: The Alvarado score was the highest cited study since 1999, with 1086 citations, making it the most impactful study in this research field of diagnostic tools to diagnose appendicitis. Due to the diversity of target populations and settings for which diagnostic tools are developed, there is a need to expand research on diagnostic tools for appendicitis.

Quality-of-life outcomes following topical melatonin application against acute radiation dermatitis in patients with early breast cancer: A double-blind, randomized, placebo-controlled trial.

The aim of this double-blind, placebo-controlled, randomized study was to investigate whether topical melatonin administered during radiation therapy could increase the quality of life in patients with primary breast cancer. Patients were followed from the first radiation fraction until 3 weeks after the last. The patients applied 1 g of cream to the irradiated area of the skin twice daily, consisting of either 25 mg/g melatonin and 150 mg/g dimethyl sulfoxide, or a placebo cream. Outcomes were the European Organisation for Research and Treatment of Cancer's quality-of-life questionnaires for breast cancer (QLQ-C30 and QLQ-BR23) on the last day of radiation therapy. As a secondary outcome, we evaluated the breast symptom (BS) scores over the entire duration of the trial in a repeated measures linear model. We included 65 patients and had 17 drop-outs, thus totaling 26 and 22 patients in the melatonin and placebo groups, respectively. BS scores on the last day of radiation did not differ between groups (p = .333). However, the linear model analyzing BS for the entire duration showed that melatonin significantly decreased the symptoms (p = .001). There was no difference in the BS score on the last day of radiation, however, we found that the patients in the melatonin group had significantly lower BS scores over the entire duration of the trial.

Effect of melatonin cream on acute radiation dermatitis in patients with primary breast cancer: A double-blind, randomized, placebo-controlled trial.

AIM: This was a double-blind, placebo-controlled randomized study investigating whether melatonin can protect against radiation dermatitis in women receiving radiation therapy for primary breast cancer. METHODS: Patients were included before radiation therapy and followed once weekly throughout treatment with a 3-week follow-up. Patients applied 1 g of cream to the irradiated skin twice daily, consisting of either 25 mg/g melatonin and 150 mg/g dimethyl sulfoxide, or placebo. Our outcomes were the Radiation Therapy Oncology Group's (RTOG) acute radiation morbidity scoring criteria for skin, a pixel analysis of erythema in clinical photographs, and patients' use of corticosteroid cream. Outcomes were evaluated once weekly throughout the trial. The primary outcomes were RTOG-score and pixel analysis at 2 weeks follow-up. Secondary outcomes were the use of corticosteroid cream and analyses of RTOG-scores and pixel analyses throughout the trial. RESULTS: Sixty-five patients were included, 17 dropped out, totaling 26 and 22 patients randomized to melatonin and placebo, respectively. RTOG-scores and pixel analyses at 2 weeks follow-up showed no difference p = .441 and p = .890, respectively). There was no difference in the use of corticosteroid cream (p = .055). Using logistic regression, the melatonin group had a higher likelihood of having a low RTOG-score (p = .0016). The logistic regression showed no difference between the groups for the pixel analyses. CONCLUSION: Our primary outcome showed no difference in RTOG-scores at 2 weeks follow-up, however, the RTOG-score over the entire duration of the study demonstrated a protective effect of melatonin. Further studies are warranted investigating higher doses of melatonin, and whether corticosteroids may influence the effect of melatonin cream against radiation dermatitis.

Varying convalescence recommendations for sport and heavy lifting after groin hernia repair: a nationwide survey among leading hernia surgeons.

BACKGROUND: Recent international hernia guidelines state that work and leisure activities after inguinal hernia repair can be resumed after a convalescence of three to five days for most patients. There is no specific recommendation for convalescence duration before resuming sport and heavy lifting. This nationwide survey aimed to assess leading hernia surgeons' recommendations for convalescence after groin hernia repair and to explore their general opinions regarding convalescence. METHODS: A validated questionnaire was sent to 32 leading groin hernia surgeons covering all Danish private and public hospitals. The primary outcome was convalescence recommendations following Lichtenstein and laparoscopic groin hernia repair for activities of daily living, light work, sport, and heavy lifting. RESULTS: A total of 29 surgeons (91%) responded to the questionnaire. The surgeons generally agreed on resuming daily activities and light work as soon as possible according to the level of pain. For resumption of sport, the surgeons recommended a median convalescence of 14 days (IQR 10-23, range 7-30) after Lichtenstein repair and 14 days (IQR 10-21, range 7-30) after laparoscopic repair. Most of the surgeons instructed patients with a defined number of days before resuming heavy lifting, which after Lichtenstein repair was median 14 days (IQR 8-28, range 2-30) and after laparoscopic repair was median 21 days (IQR 14-30, range 7-30). None of the surgeons routinely prescribed sick leave. Seventeen surgeons (61%) thought that recommending a too short convalescence could cause complications, primarily recurrence, hematoma, and pain. CONCLUSION: This study revealed that surgeons agreed on the resumption of daily activities and light work as soon as possible according to the level of pain. However, a broad spectrum of convalescence recommendations was revealed for sport and heavy lifting.

Many diagnostic tools for appendicitis: a scoping review.

BACKGROUND: We aimed to provide an overview of all diagnostic tools developed to diagnose appendicitis with their reported accuracy and to further characterize these including their need for diagnostic equipment. METHODS: This scoping review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews and a protocol was registered at Open Science Framework. We performed a systematic literature search in PubMed, Embase, China National Knowledge Infrastructure, Índice Bibliográfico Espanhol de Ciências da Saúde, and Latin American and Caribbean Health Sciences Literature. We included original articles of all languages with the purpose to derive an accessible diagnostic tool. We extracted data regarding study- and diagnostic tool characteristics, and the accuracy of each diagnostic tool. RESULTS: The search led to 6419 records, where 74 studies were included, yielding 82 diagnostic tools reported in seven different languages. Among these tools, 35% included patient characteristics, 85% symptoms, 93% physical examinations, 37% vital signs, 78% laboratory values, and 16% imaging. Among the diagnostic tools, 35% relied on a medical doctor/surgeon with access to a laboratory, and six diagnostic tools did not require a bedside medical doctor/surgeon. The median positive predictive value, negative predictive value, sensitivity, and specificity across diagnostic tools were 91%, 94%, 89%, and 86%, respectively. CONCLUSIONS: We identified 82 diagnostic tools that most frequently were based on symptoms and physical examinations. Most diagnostic tools relied on a medical doctor/surgeon with access to laboratory values. The accuracy was high across the diagnostic tools.

Mesh versus non-mesh for emergency groin hernia repair.

BACKGROUND: A groin hernia is a collective name for inguinal and femoral hernias, which can present acutely with incarceration or strangulation of the hernia sac content, requiring emergency treatment. Timely repair of emergency groin hernias is crucial due to the risk of reduced blood supply and thus damage to the bowel, but the optimal surgical approach is unclear. While mesh repair is the standard treatment for elective hernia surgery, using mesh for emergency groin hernia repair remains controversial due to the risk of surgical site infection. OBJECTIVES: To assess the benefits and harms of mesh compared with non-mesh in emergency groin hernia repair in adult patients with an inguinal or femoral hernia. SEARCH METHODS: On 5 August 2022, we searched the following databases: CENTRAL, MEDLINE Ovid, and Embase Ovid, as well as two trial registers for ongoing and completed trials. Additionally, we performed forward and backward citation searches for the included trials and relevant review articles. We searched without any language or publication restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing mesh with non-mesh repair in emergency groin hernia surgery in adults. We included any mesh and any non-mesh repairs. All studies fulfilling the study, participant, and intervention criteria were included irrespective of reported outcomes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. We presented dichotomous data as risk ratios (RR) with 95% confidence intervals (CI). We based missing data analysis on best- and worst-case scenarios. For outcomes with sufficiently low heterogeneity, we performed meta-analyses using the random-effects model. We analysed subgroups when feasible, including the degree of contamination. We used RoB 2 for risk of bias assessment, and summarised the certainty of evidence using GRADE. MAIN RESULTS: We included 15 trials randomising 1241 participants undergoing emergency groin hernia surgery with either mesh (626 participants) or non-mesh hernia repair (615 participants). The studies were conducted in China, the Middle East, and South Asia. Most patients were men, and most participants had an inguinal hernia (41 participants had femoral hernias). The mean/median age in the mesh group ranged from 35 to 70 years, and from 41 to 69 years in the non-mesh group. All studies were performed in a hospital emergency setting (tertiary care) and lasted for 11 to 139 months, with a median study duration of 31 months. The majority of the studies only included participants with clean to clean-contaminated surgical fields. For all outcomes, we considered the certainty of the evidence to be very low, mainly downgraded due to high risk of bias (due to deviations from intended intervention and missing outcome data), indirectness, and imprecision. Mesh hernia repair may have no effect on or slightly increase the risk of 30-day surgical site infections (RR 1.66, 95% CI 0.96 to 2.88; I² = 21%; 2 studies, 454 participants) when compared with non-mesh hernia repair, but the evidence is very uncertain. The evidence is also very uncertain about the effect of mesh hernia repair compared with non-mesh hernia repair on 30-day mortality (RR 1.38, 95% CI 0.58 to 3.28; 1 study, 208 participants). In summary, the results showed 70 more (from 5 fewer to 200 more) surgical site infections and 29 more (from 32 fewer to 175 more) deaths within 30 days of mesh hernia repair per 1000 participants compared with non-mesh hernia repair. The evidence is very uncertain about 90-day surgical site infections after mesh versus non-mesh hernia repair (RR 1.00, 95% CI 0.15 to 6.64; 1 study, 60 participants; very low-certainty evidence). No 30-day recurrences were recorded, and mesh hernia repair may not reduce recurrence within one year (RR 0.19, 95% CI 0.04 to 1.03; I² = 0%; 2 studies, 104 participants; very low-certainty evidence). Within 30 days of hernia repair, no meshes were removed from clean to clean-contaminated fields, but 6.7% of meshes (1 study, 208 participants) were removed from contaminated to dirty surgical fields. Among the four studies reporting 90-day mesh removal, no events occurred. We were not able to identify any studies reporting complications classified according to the Clavien-Dindo Classification or reoperation for complications within 30 days of repair. AUTHORS' CONCLUSIONS: Our results show that in terms of 30-day surgical site infections, 30-day mortality, and hernia recurrence within one year, the evidence for the use of mesh hernia repair compared with non-mesh hernia repair in emergency groin hernia surgery is very uncertain. Unfortunately, firm conclusions cannot be drawn due to very low-certainty evidence and meta-analyses based on small-sized and low-quality studies. There is a need for future high-quality RCTs or high-quality registry-based studies if RCTs are unfeasible.

Low incidence of recurrence and chronic pain after groin hernia repair in adolescents: a systematic review and meta-analysis.

PURPOSE: The best operative management of groin hernia in adolescents is uncertain. The aim of this systematic review was to assess recurrence and chronic pain after mesh versus non-mesh repair for groin hernia in adolescents. METHODS: A systematic search was done in PubMed, EMBASE, and Cochrane CENTRAL in May 2022 for studies reporting postoperative chronic pain (≥6 months) or recurrence after groin hernia repair in adolescents aged 10-17 years. We included randomized controlled trials and observational studies on primary unilateral or bilateral groin hernia repair. Risk of bias was assessed with the Cochrane risk-of-bias tool and Newcastle-Ottawa Scale. Meta-analysis of the incidence of recurrence was conducted. This review is reported according to PRISMA guideline. RESULTS: A total of 21 studies including 3,816 adolescents with groin hernias were included comprising two randomized controlled trials, six prospective, and 13 retrospective cohort studies. For non-mesh repairs, the weighted mean incidence proportion of recurrence was 1.6% (95% CI 0.6-2.5) after 2,167 open repairs and 1.9% (95% CI 1.1-2.8) after 1,033 laparoscopic repairs. For mesh repairs, it was 0.6% (95% CI 0.0-1.4) after 406 open repairs while there were no recurrences after 347 laparoscopic repairs (95% CI 0.0-0.6). Across all surgical techniques, the rate of chronic pain after 1,153 repairs ranged from 0 to 11%. Follow-up time varied and was reported in various ways. CONCLUSION: The incidences of recurrence after groin hernia repair in adolescents were low for both open and laparoscopic mesh and non-mesh repairs. Rates of postoperative chronic pain were low. TRIAL REGISTRATION: PROSPERO: CRD42022130554.

Other Pathologies Were Rarely Reported after Laparoscopic Surgery for Suspected Appendicitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Diagnostic laparoscopy is often used when a patient is suspected of having acute appendicitis. The aim of this study was to assess the rate of other pathologies found during diagnostic laparoscopy for suspected acute appendicitis. METHODS: This systematic search included studies with ≥100 patients who received laparoscopy for suspected acute appendicitis and reported on the histopathologic and other intra-abdominal findings. We performed a meta-analysis estimating the rate of other pathologies, and a sensitivity analysis excluding smaller cohorts (≤500 patients). Age groups, sex, specific findings, and geographic regions were investigated. Certainty of evidence was assessed with GRADE. RESULTS: A total of 27 studies were included covering 25,547 patients and of these 793 had an unexpected pathology. The findings were benign pathology in the appendix (34%), malignancy (30%), gynecologic pathology (5%), gastrointestinal pathology (4%), or unspecified (27%). Meta-analysis showed an overall rate of unexpected findings of 3.5% (95% CI 2.7-4.3; moderate certainty), and the sensitivity analysis showed similar results. Malignancy found in the appendix when treating suspected acute appendicitis was 1.0% (95% CI 0.8-1.3%; high certainty). CONCLUSION: The rate of other histopathological findings in patients with suspected acute appendicitis was low and a malignancy in appendix was found in 1% of patients.

Nerve identification during open inguinal hernia repair: a systematic review and meta-analyses.

PURPOSE: Inguinal hernia repair is one of the most common operations worldwide and despite this, the incidence of chronic pain remains high after inguinal hernia repair. The optimal nerve handling strategy is controversial and the rate at which nerves are identified remains uncertain. This study aimed to determine the identification rates of the ilioinguinal, iliohypogastric, and genitofemoral nerves as well as nerve handling strategies. METHODS: This review was registered on PROSPERO (CRD 42023416576). PubMed, Embase, and Cochrane Central were systematically searched. Studies with more than 10 patients were included if they reported an identification rate for at least one of the nerves during elective open inguinal hernia repair in adults. Studies requiring nerve identification in their study design were excluded. Bias was assessed with the JBI critical appraisal tool and Cochrane's RoB-2 tool. The overall estimate of the prevalence was analysed with prevalence meta-analyses. RESULTS: A total of 23 studies were included. The meta-analyses included 18 studies, which resulted in an identification rate of 82% (95% CI: 76-87%) for the ilioinguinal nerve, 62% (95% CI: 54-71%) for the iliohypogastric nerve, and 41% (95% CI: 27-55%) for the genitofemoral nerve. Nerves were spared in 82% of all repairs. CONCLUSION: The ilioinguinal, iliohypogastric, and genitofemoral nerves were identified in 82%, 62%, and 41% of surgeries, respectively. Most studies used a nerve-preserving strategy. The role of nerve identification in the development of chronic pain remains uncertain, as well as the optimal nerve handling strategy.

Varying negative appendectomy rates after laparoscopic appendectomy: a systematic review and meta-analysis.

PURPOSE: Appendicitis is a common cause of acute abdominal pain, and treatment with laparoscopy has become increasingly common during the past two decades. Guidelines recommend that normal appendices are removed if operated for suspected acute appendicitis. It is unclear how many patients are affected by this recommendation. The aim of this study was to estimate the rate of negative appendectomies in patients undergoing laparoscopic surgery for suspected acute appendicitis. METHODS: This study was reported following the PRISMA 2020 statement. A systematic search was conducted in PubMed and Embase for retrospective or prospective cohort studies (with n ≥ 100) including patients with suspected acute appendicitis. The primary outcome was the histopathologically confirmed negative appendectomy rate after a laparoscopic approach with a 95% confidence interval (CI). We performed subgroup analyses on geographical region, age, sex, and use of preoperative imaging or scoring systems. The risk of bias was assessed using the Newcastle-Ottawa Scale. Certainty of the evidence was assessed using GRADE. RESULTS: In total, 74 studies were identified, summing up to 76,688 patients. The negative appendectomy rate varied from 0% to 46% in the included studies (interquartile range 4-20%). The meta-analysis estimated the negative appendectomy rate to be 13% (95% CI 12-14%) with large variations between the individual studies. Sensitivity analyses did not change the estimate. The certainty of evidence by GRADE was moderate due to inconsistency in point estimates. CONCLUSION: The overall estimated negative appendectomy rate after laparoscopic surgery was 13% with moderate certainty of evidence. The negative appendectomy rate varied greatly between studies.

Individual biomarkers in the blood are not yet applicable in diagnosing complicated appendicitis: A scoping review.

BACKGROUND: Appendicitis is one of the most common surgical emergencies globally and it can both be difficult to diagnose but also to differentiate complicated from uncomplicated appendicitis preoperatively. The objective of this scoping review was to develop an overview of biomarkers in blood discriminating complicated from uncomplicated appendicitis and characterize their applicability in an acute setting including time, cost, and analysis technique required as well as their individual precision. METHOD: This scoping review was reported in accordance with PRISMA-ScR. The included studies had to report on biomarkers measured in the blood for at least ten patients with suspected appendicitis. A systematic literature search was conducted on August 28, 2022, in PubMed and Embase but restricted to articles published in January 2000 and onwards. A protocol was uploaded to Open Science Framework prior to data extraction. RESULTS: A total of 65 biomarkers were included from 52 studies, covering 14,312 patients. There was 60% routine- and 40% novel biomarkers based on the reported analysis technique. The most frequently investigated biomarkers within each group were white blood cell count and procalcitonin. The routine biomarkers were of low financial cost but poor diagnostic accuracy with sensitivity ranging between 15 and 100% and specificity between 27 and 100%. Novel markers were costly ranging from 275 to 800$, and their diagnostic accuracy was based on limited population sizes (median 34 patients) and reported for only 5% of the novel markers. CONCLUSION: Routine biomarkers were applicable in an acute setting but had poor diagnostic accuracy. Novel biomarkers are being investigated for potential, but the concept is still premature due to lack of diagnostic accuracy studies reporting cost-benefit for individual markers and whether they can be applied in an acute setting.

Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti-phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS). OBJECTIVE: To compare APA levels (anti-cardiolipin, anti-phosphatidylethanolamine (anti-PE), and anti-ß2 -glycoprotein (anti-B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti-dsDNA IgG and markers of coagulation. METHODS: Patient specimens were assayed for APA IgG, anti-dsDNA IgG and thrombin-anti-thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical-mechanical coagulometer. RESULTS: Anti-cardiolipin IgG in NP was 5-fold higher than control tissue (p < .0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 µg/mL (36.7 s vs. 33.8 s, p = .024) and 600 µg/mL (40.9 s vs. 34.7 s, p = .0037). Anti-PE IgG antibodies were increased in NP (p = .027), but anti-B2GP IgG was not significantly higher (p = .084). All APAs correlated with anti-dsDNA IgG levels, which were also elevated (R = .77, .71 and .54, respectively, for anti-cardiolipin, anti-PE, and anti-B2GP; all p < .001), but only anti-cardiolipin (R = .50, p = .0185) and anti-PE (R = 0.45, p = .037) correlated with TaT complex levels. CONCLUSIONS: APA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti-coagulant activity similar to those observed in anti-phospholipid syndrome, suggesting that they may have pro-coagulant effects in polyp tissue.

Mesenteric Lymphadenitis and Terminal Ileitis is Associated With Yersinia Infection: A Meta-analysis.

BACKGROUND: Yersinia infection affects terminal ileum and lymph nodes and could therefore mimic the symptoms of appendicitis. We aimed to systematically characterise the suspected or confirmed abdominal diseases and/or surgeries associated with Yersinia infection. MATERIALS AND METHODS: This systematic review and meta-analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A protocol (CRD42016053252) was uploaded to PROSPERO. The searches were conducted in PubMed and EMBASE on October 2, 2020. Original reports on patients with abdominal surgical diseases were included. The primary outcome was to characterise suspected or confirmed abdominal surgical diseases and/or surgeries associated with Yersinia infection, while the secondary outcomes were the positive rate of Yersinia species for each disease and surgery, and to investigate the rate of Yersinia spp. in different geographic regions. We calculated the weighted mean prevalence of positive tests for Yersinia spp. for the different diseases and surgeries according to the detection method and for subgroups based on geographic region. RESULTS: From the search, 33 studies were included in the systematic review and 18 in the meta-analysis. Across geographic regions, the weighted mean prevalence for Yersinia spp. was 51% (95% CI 34%-69%) in mesenteric lymphadenitis, 65% (95% CI 45%-85%) in terminal ileitis, and 8% (95% CI 2%-15%) in normal appendices. CONCLUSIONS: Around half of the patients with mesenteric lymphadenitis and terminal ileitis were serologically positive for infections with Yersinia spp. Yersinia infection may cause unnecessary surgery for suspected appendicitis due to symptoms from mesenteric lymphadenitis or terminal ileitis.