Enteral Access Outcomes in Patients Hospitalized With Cardiac Disease: A Retrospective Cohort Study.

INTRODUCTION: Patients admitted with principal cardiac diagnosis (PCD) can encounter difficult inpatient stays that are often marked by malnutrition. In this setting, enteral feeding may improve nutritional status. This study examined the association of PCD with perioperative outcomes after elective enteral access procedures. METHODS: Adult patients who underwent enteral access procedures between 2018 and 2020 at a tertiary care institution were reviewed retrospectively. Differences in baseline characteristics between patients with and without PCD were adjusted using entropy balancing. Multivariable logistic and linear regressions were subsequently developed to evaluate the association between PCD and nutritional outcomes, perioperative morbidity and mortality, length of stay, and nonelective readmission after enteral access. RESULTS: 912 patients with enteral access met inclusion criteria, of whom 84 (9.2%) had a diagnosis code indicating PCD. Compared to non-PCD, patients with PCD more commonly received percutaneous endoscopic gastrostomy by general surgery and had a higher burden of comorbidities as measured by the Charlson comorbidity index. Multivariable risk adjustment generated a strongly balanced distribution of baseline covariates between patient groups (standardized differences ranged from -2.45 × 10-8 to 3.18 × 108). After adjustment, despite no significant association with in-hospital mortality, percentage change prealbumin, length of stay, or readmission, PCD was associated with an approximately 2.25-day reduction in time to meet goal feeds (95% CI -3.76 to -0.74, P = 0.004) as well as decreased odds of reoperation (adjusted odds ratio 0.28, 95% CI 0.09-0.86, P = 0.026) and acute kidney injury (adjusted odds ratio 0.24, 95% CI 0.06-0.91, P = 0.035). CONCLUSIONS: Despite having more comorbidities than non-PCD, adult enteral access patients with PCD experienced favorable nutritional and perioperative outcomes.

Discovering genetic determinants for cell-to-cell adhesion in two prevalent conjugative lactococcal plasmids.

Plasmids pNP40 and pUC11B encode two prevalent yet divergent conjugation systems, which have been characterized in detail recently. Here, we report the elucidation of the putative adhesins of the pNP40 and pUC11B conjugation systems, encoded by traAd and trsAd, respectively. Despite their significant sequence divergence, TraAd and TrsAd represent the most conserved component between the pNP40- and the pUC11B-encoded conjugation systems and share similar peptidoglycan-hydrolase domains. Protein structure prediction using AlphaFold2 highlighted the structural similarities between their predicted domains, as well as the potential homo-dimeric state of both proteins. Expression of the putative surface adhesins resulted in a cell clumping phenotype not only among cells expressing these surface adhesins but also between adhesin-expressing and non-producing cells. Furthermore, mutant derivatives of plasmids pNP40 or pUC11B carrying a mutation in traAd or trsAd, respectively, were shown to act as efficient donors provided the corresponding recipient expresses either traAd or trsAd, thus demonstrating in trans reciprocal complementarity of these proteins in conjugation systems.

Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. AIM: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. CLINICAL IMPLICATIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.

Sleeve Gastrectomy Reduces the Need for Liver Transplantation in Patients with Obesity and Non-Alcoholic Steatohepatitis: a Predictive Model.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the leading indications for liver transplantation (LT) in the United States. As with the current obesity epidemic, the incidence of NASH continues to rise. However, the impact of broad utilization of bariatric surgery (BS) for patients with NASH is unknown, particularly in regard to mitigating the need for LT. METHODS: Markov decision analysis was performed to simulate the lives of 20,000 patients with obesity and concomitant NASH who were deemed ineligible to be waitlisted for LT unless they achieved a body mass index (BMI) < 35 kg/m2. Life expectancy following medical weight management (MWM) and sleeve gastrectomy (SG) were estimated. Base case patients were defined as having NASH without fibrosis and a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: Simulated base case analysis patients who underwent SG gained 14.3 years of life compared to patients who underwent MWM. One year after weight loss intervention, 9% of simulated MWM patients required LT compared to only 5% of SG patients. Survival benefit for SG was observed above a BMI of 32.2 kg/m2. CONCLUSION: In this predictive model of 20,000 patients with obesity and concomitant NASH, surgical weight loss is associated with a reduction in the progression of NASH, thereby reducing the need for LT. A reduced BMI threshold of 32 kg/m2 for BS may offer survival benefit for patients with obesity and NASH.

Transcriptional control of two distinct lactococcal plasmid-encoded conjugation systems.

Lactococcal conjugative plasmids are poorly characterized compared to those harbored by numerous other Gram-positive bacteria, despite their significance in dairy fermentations and starter culture development. Furthermore, the transcriptional landscape of these lactococcal conjugation systems and their regulation have not been studied in any detail. Lactococcal plasmids pNP40 and pUC11B possess two genetically distinct and prevalent conjugation systems. Here, we describe the detailed transcriptional analysis of the pNP40 and pUC11B conjugation-associated gene clusters, revealing three and five promoters, respectively, for which the corresponding transcriptional start sites were identified. Regulation of several of these promoters, and therefore conjugation, is shown to involve the individual or concerted activities of the corresponding relaxase and transcriptional repressor(s) encoded by each conjugative plasmid. This work highlights how the conjugative potential of these systems may be unlocked, with significant implications for the starter culture and food fermentation industry.

A Systematic Review of Immersive Virtual Reality for Nontechnical Skills Training in Surgery.

OBJECTIVE: Immersive virtual reality (IVR) can be utilized to provide low cost and easily accessible simulation on all aspects of surgical education. In addition to technical skills training in surgery, IVR simulation has been utilized for nontechnical skills training in domains such as clinical decision-making and pre-operative planning. This systematic review examines the current literature on the effectiveness of IVR for nontechnical skill acquisition in surgical education. DESIGN: A literature search was performed using MEDLINE, EMBASE, and Web of Science for primary studies published between January 1, 1995 and February 9, 2022. Four reviewers screened titles, abstracts, full texts, extracted data, and analyzed included studies to answer 5 key questions: How is IVR being utilized in nontechnical skills surgical education? What is the methodological quality of studies? What technologies are being utilized? What metrics are reported? What are the findings of these studies? RESULTS: The literature search yielded 2340 citations, with 12 articles included for qualitative synthesis. Of included articles, 33% focused on clinical decision-making and 67% on anatomy/pre-operative planning. Motion sickness was a recorded metric in 25% of studies, with an aggregate incidence of 13% (11/87). An application score was reported in 33% and time to completion in 16.7%. A commercially developed application was utilized in 25%, while 75% employed a noncommercial application. The Oculus Rift was used in 41.7% of studies, HTC Vive in 25%, Samsung Gear in 16.7% of studies, Google Daydream in 8%, and 1 study did not report. The mean Medical Education Research Quality Instrument (MERSQI) score was 10.3 ± 2.3 (out of 18). In all studies researching clinical decision-making, participants preferred IVR to conventional teaching methods and in a nonrandomized control study it was found to be more effective. Averaged across all studies, mean scores were 4.33 for enjoyment, 4.16 for utility, 4.11 for usability, and 3.73 for immersion on a 5-point Likert scale. CONCLUSIONS: The IVR nontechnical skills applications for surgical education are designed for clinical decision-making or anatomy/pre-operative planning. These applications are primarily noncommercially produced and rely upon a diverse array of HMDs for content delivery, suggesting that development is primarily coming from within academia and still without clarity on optimal utilization of the technology. Excitingly, users find these applications to be immersive, enjoyable, usable, and of utility in learning. Although a few studies suggest that IVR is additive or superior to conventional teaching or imaging methods, the data is mixed and derived from studies with weak design. Motion sickness with IVR remains a complication of IVR use needing further study to determine the cause and means of mitigation.

Ventricular Remodeling Following Metabolic and Bariatric Surgery Decreases Need for Heart Transplantation: A Predictive Model.

PURPOSE: For patients with obesity and congestive heart failure (CHF) who require heart transplantation (HT), aggressive weight loss has been associated with ventricular remodeling, or subclinical alterations in left and right ventricular structure that affect systolic function. Many have suggested offering metabolic and bariatric surgery (MBS) for these patients. As such, we evaluated the role of MBS in HT for patients with obesity and CHF using predictive modelling techniques. MATERIALS AND METHODS: Markov decision analysis was performed to simulate the life expectancy of 30,000 patients with concomitant obesity, CHF, and 30% ejection fraction (EF) who were deemed ineligible to be waitlisted for HT unless they achieved a BMI < 35 kg/m2. Life expectancy following diet and exercise (DE), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: RYGB patients had lower rates of HT and received HT quicker when needed. Base case patients who underwent RYGB gained 2.2 additional mean years survival compared with patients who underwent SG and 10.3 additional mean years survival compared with DE. SG patients gained 6.2 mean years of life compared with DE. CONCLUSION: In this simulation of 30,000 patients with obesity, CHF, and reduced EF, MBS was associated with improved survival by not only decreasing the need for transplantation due to improvements in EF, but also increasing access to HT when needed due to lower average BMI.

Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health.

BACKGROUND: In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. AIM: In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. METHOD: A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. OUTCOMES: Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. RESULTS: An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. CLINICAL IMPLICATIONS: Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. STRENGTHS AND LIMITATIONS: Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. CONCLUSION: The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

Ethical Guidance for Physicians and Health Care Institutions on Grateful Patient Fundraising: A Position Paper From the American College of Physicians.

Physician solicitation of charitable contributions from patients-also known among other things as grateful patient fundraising-raises significant ethical concerns. These include pressure on patients to donate and the effects of this on the patient-physician relationship, potential expectations of donor patients for treatment that is not indicated or preferential care, justice and fairness issues, disclosure and use of confidential patient information for nontreatment purposes, and conflicts of interest. The patient-physician relationship and knowledge of the patient's medical history, clinical status, personal information, and financial circumstances are some of the reasons development and administrative officials might see physicians as strong potential fundraisers. But those are among the reasons grateful patient fundraising is ethically problematic. This American College of Physicians position paper explores these issues and offers guidance.

Factors associated with conversion in laparoscopic surgery in a low-resource setting: a single-center prospective study.

INTRODUCTION: Laparoscopy has a clear patient benefit related to postoperative morbidity but may not be as commonly performed in low-and middle-income countries. The decision to convert to laparotomy can be complex and involve factors related to the surgeon, patient, and procedure. The objective of this work is to analyze the factors associated with conversion in laparoscopic surgery in a low-resource setting. METHODS: This is a single-center prospective study of patients who underwent laparoscopic surgery between May 1, 2018 and October 31, 2021. The parameters studied were age, sex, body mass index (BMI), intraoperative complication (e.g., accidental enterotomy, hemorrhage), equipment malfunction (e.g., technical failure of the equipment, break in CO2 supply line), operating time, and conversion rate. RESULTS: A total of 123 laparoscopic surgeries were performed. The average age of patients was 31.2 years (range 11-75). The procedures performed included appendix procedures (48%), followed by gynecological (18.7%), gallbladder (14.6%), digestive (10.56%), and abdominal procedures (4%). The average length of hospitalization was 3 days (range 1-16). Conversion to laparotomy was reported in 8.9% (n = 11) cases. Equipment malfunction was encountered in 9.8% (n = 12) cases. Surgical complications were noted in 11 cases (8.9%). Risk factors for conversion were shown to be BMI > 25 kg/m2 (OR 4.6; p = 0.034), intraoperative complications (OR 12.6; p = 0.028), and equipment malfunction (OR 9.4; p = 0.002). CONCLUSION: A better understanding of the underlying factors associated with high conversion rates, such as overweight/obesity, intraoperative complications, and equipment failure, is the first step toward surgical planning to reduce postoperative morbidity in low-resource settings.

Evolution of laparoscopic surgery in a sub-Saharan African country: a 30-year literature review in Senegal.

INTRODUCTION: The advent of laparoscopy has significantly reduced the morbidity associated with the majority of abdominal surgeries. In Senegal, the first studies evaluating this technique were published in the 1980s. The objective of this systematic review is to assess the evolution of laparoscopy research in Senegal. METHODS: A search of PubMed and Google Scholar was carried out without limit of publication date. The keywords used were "senegal" AND "laparoscop*". Duplicates were removed, and remaining articles were assessed for selection criteria. We included all articles about laparoscopy published in Senegal. The parameters studied in each included article were the place and year of study, average age, sex ratio, assessed indications and results. RESULTS: 41 Studies published between 1984 and 2021 met selection criteria. The average age of patients was 33 years (range 4.7-63). The sex ratio was 0.33. The main indications for laparoscopy according to the studies were: benign gastrointestinal disorders in 11 studies (26.8%), abdominal emergencies in 9 studies (22%), gallbladder surgery in 5 studies (12.2%), benign gynecological pathology in 6 studies (14.6%), malignant gynecological pathology in 2 studies (4.9%), diagnostic laparoscopy in 2 studies (4.9%), groin hernia repair in 2 studies (4.9%) and testicular pathology in 1 study (2.4%). Overall mortality was estimated at 0.9% (95% CI 0.6-1.3) and overall morbidity for all complications was estimated at 5% (95% CI 3.4-6.9). CONCLUSIONS: This systematic review showed a predominance of the laparoscopy publications from the capital in Dakar with favorable outcomes. This technique should be popularized in the different regions of the country and its indications expanded.

Evaluation of the educational quality of publicly available online videos on laparoscopic jejunostomy by utilizing the LAP-VEGaS guidelines.

BACKGROUND: Despite its common nature, there is no data on the educational quality of publicly available laparoscopic jejunostomy training videos. The LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool, released in 2020, has been developed to ensure that teaching videos are of appropriate quality. This study applies the LAP-VEGaS tool to currently available laparoscopic jejunostomy videos. METHODS: A retrospective review of YouTube® videos was conducted for "laparoscopic jejunostomy." Included videos were rated by three independent investigators using LAP-VEGaS video assessment tool (0-18). Wilcoxon rank-sum test was used to evaluate differences in LAP-VEGaS scores between video categories and date of publication relative to 2020. Spearman's correlation test was performed to measure association between scores and length, number of views and likes. RESULTS: 27 unique videos met selection criteria. Academic and physician video walkthroughs did not demonstrate a significant difference in median scores (9.33 IQR 6.33, 14.33 vs. 7.67 IQR 4, 12.67, p = 0.3951). Videos published after 2020 demonstrated higher median scores than those published before 2020 (13 IQR 7.5, 14.67 vs. 5 IQR 3, 9.67, p = 0.0081). A majority of videos failed to provide patient position (52%), intraoperative findings (56%), operative time (63%), graphic aids (74%), and audio/written commentary (52%). A positive association was demonstrated between scores and number of likes (rs = 0.59, p = 0.0011) and video length (rs = 0.39, p = 0.0421), but not number of views (rs = 0.17, p = 0.3991). CONCLUSION: The majority of available YouTube® videos on laparoscopic jejunostomy fail to meet the basic educational needs of surgical trainees, and there is no difference between those produced by academic centers or independent physicians. However, there has been improvement in video quality following the release of the scoring tool. Standardization of laparoscopic jejunostomy training videos with the LAP-VEGaS score can ensure that videos are of appropriate educational value with logical structure.

What are trainees watching? Assessing the educational quality of online laparoscopic cholecystectomy training videos using the LAP-VEGaS guidelines.

BACKGROUND: Laparoscopic cholecystectomy is the most common laparoscopic procedure performed in the US and a key component of general surgery training. Surgical trainees frequently access YouTube for educational walkthroughs of surgical procedures. This study aims to evaluate the educational quality of YouTube video walkthroughs on laparoscopic cholecystectomy by using the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool. METHODS: A YouTube search was conducted using "laparoscopic cholecystectomy." Results were sorted by relevance, and the top 100 videos were gathered. Videos with patient education or concomitant procedures were excluded. Included videos were categorized as Physician (produced by an individual physician), Academic (produced by a university or medical school), Commercial (produced by a surgical company), and Society (produced by a professional surgical society) and were rated by 3 investigators using the LAP-VEGaS video assessment tool (0-18). RESULTS: In all, 33 videos met the selection criteria. The average LAP-VEGaS score was 7.96 ± 3.95, and inter-rater reliability was .86. Academic videos demonstrated a significantly higher mean LAP-VEGaS score than Commercial (10.69 ± 3.54 vs 5.25 ± 2.38, P = .033). Most academic videos failed to provide formal case presentations (63%), patient positioning (50%), intraoperative findings (50%), graphic aids (63%), and operative time (75%). CONCLUSION: This is the first study to evaluate the quality of YouTube video walkthroughs on LC using the LAP-VEGaS tool. Despite demonstrating higher LAP-VEGaS scores than other categories, video walkthroughs provided by academic institutions still lack several essential educational criteria for this procedure, highlighting areas of improvement for educators.

Vestibular tissue changes following administration of intravaginal prasterone: a vulvoscopic open-label pilot study in menopausal women with dyspareunia.

Background: Prasterone, an intravaginal dyspareunia treatment in menopausal women, improves vaginal health through intracellular conversion of dehydroepiandrosterone into androgens and estrogens. Phase 3 trials for prasterone showed significant improvement in vaginal tissue health and reduction of pain. Aim: To assess vestibular changes with daily use of intravaginal prasterone in menopausal women with moderate to severe dyspareunia. Methods: This open-label prospective pilot study was conducted over 20 weeks. It included 11 menopausal women (median age, 56 years) who were treated daily with intravaginal inserts of 6.5-mg prasterone and assessed monthly. During vulvoscopy, vestibular pain was assessed by cotton-tipped swab testing, and vestibular and vaginal health was independently assessed with the Visual Scale (VS). In addition, vulvoscopic photographs were obtained and assessed via the Vulvoscopic Genital Tissue Appearance (VGTA) scale to evaluate overall genital tissue health. Mean changes from baseline for genital tissue health and pain assessments were analyzed by repeated measures 1-way analysis of variance, followed by a Dunnett post hoc test. Sexual event diaries were completed and adverse events recorded. Outcomes: Outcomes included indices of genital tissue health: pain assessment by cotton-tipped swab testing, VS of the vestibule and vagina, VGTA, and sexual event diary. Results: Aggregate scores from the cotton-tipped swab test progressively improved, reaching statistical significance at week 16, which was maintained through week 20 (-7.27, P = .019). VS scores significantly improved from baseline by week 4 and were maintained through week 20 for the vestibule (-3.00, P = .004) and vagina (-4.00, P = .002). An overall 1607 vulvoscopic photographs were examined; all showed reduction in vestibular erythema and pallor at the end of the study. The mean change from baseline at week 20 for the VGTA score was -7.9 (P = .0016). Intercourse associated with pain was reduced from 81.3% of initiated events during the first month of the study to 8.3% during the last month. Sexual activities that were discontinued due to discomfort were reduced from 45.8% to 6.3%. No prasterone-related serious adverse events were reported. Clinical Implications: Prasterone, a safe and effective intravaginal hormone treatment, significantly improves vestibular health parameters. Strengths and Limitations: Strengths are the prospective study design and the use of multiple outcome measures to assess vestibular tissue health and pain associated with sexual activity. Limitations are the small study cohort and use of nonvalidated outcome measures. Conclusion: Our findings suggest that intravaginal prasterone exerts biologic activity on the androgenic endodermal vestibule, as the medication passes from vagina to vestibule, resulting in amelioration of pain associated with sexual activity.

Incidence, characteristics, management and outcome of patients with follicular lymphoma with tumor epidural compression, a study on 22 cases.

PURPOSE: Follicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression. MATERIAL AND METHODS: Observational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000-2021). RESULTS: Between 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range=[1-216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47-90%) of patients. The median PFS was of 36 months (95% CI 24-NA) and 5 years OS estimate was 79% (95% CI 62-100%). Two patients developed a relapse at a second epidural site. CONCLUSION: FL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.

Conversion to Roux-En-Y Gastric Bypass: a successful means of mitigating reflux after laparoscopic sleeve gastrectomy.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) has become the most common bariatric procedure due to the technical ease and weight loss success of the operation. However, there has been concern that LSG contributes to gastroesophageal reflux disease (GERD) postoperatively with a proportion of patients requiring conversion to a Roux-En-Y Gastric Bypass (RYGB). The objective of this study was to characterize the patients who underwent revision in our hospital system and to better understand pre-operative predictors of GERD and revision. METHODS: After IRB approval, a retrospective review was conducted assessing for patients who had conversion of LSG to RYGB at three hospitals within the University of Pennsylvania Health System from January 2015 to December 2021. The patients' charts were then reviewed to evaluate for demographics, BMI, operative findings, imaging and endoscopic reports, and post-operative outcomes. RESULTS: 97 patients were identified who underwent conversion of LSG to RYGB between January 2015 and December 2021. The cohort was predominantly female (n = 89, 91.7%) with an average age of 42.7 ± 10.6 years at the time of conversion. The most common indications for revision were GERD (72.2%) and obesity/insufficient weight loss (24.7%). Patients lost an average of 11.1 ± 12.9 kg after revision to RYGB. Of the patients who underwent revision for GERD, 80.2% noted global symptomatic improvement after revision and 19.4% were able to stop their proton pump inhibitor (PPI) postoperatively, with most patients decreasing the frequency of the PPI use postoperatively. CONCLUSION: The majority of patients who underwent conversion from LSG to RYGB due to GERD and saw marked improvements in GERD symptoms and outcomes. These findings illuminate the real-world practices and outcomes of bariatric revisional procedures for reflux and the need for more research on standardized practice.

[Peripheral neuropathies during systemic diseases: Part II (vasculitis)]. / Neuropathies périphériques au cours des maladies de système : partie II (vascularites).

Primary systemic vasculitides, mainly of the small and medium-sized vessels, are frequently associated with peripheral neuropathies. When the disease is already known, the appearance of a neuropathy should suggest a specific injury, especially when associated with other systemic manifestations. Conversely, when neuropathy is inaugural, close collaboration between neurologists and internists is necessary to reach a diagnosis. A standardized electro-clinical investigation specifying the topography, the evolution and the mechanism of the nerve damage enables the positive diagnosis of the neuropathy. Several elements orient the etiological diagnosis and allow to eliminate the main differential diagnosis: non systemic vasculitic neuropathy. The existence of associated systemic manifestations (glomerular or vascular nephropathy, interstitial lung disease, intra-alveolar hemorrhage, ENT involvement…), biological markers (ANCA, cryoglobulinemia, rheumatoid factor), and invasive examinations allowing histological analysis (neuromuscular biopsy) are all useful tools for.

Delineation of a lactococcal conjugation system reveals a restriction-modification evasion system.

Plasmid pUC11B is a 49.3-kb plasmid harboured by the fermented meat isolate Lactococcus lactis subsp. lactis UC11. Among other features, pUC11B encodes a pMRC01-like conjugation system and tetracycline-resistance. In this study, we demonstrate that this plasmid can be conjugated at high frequencies to recipient strains. Mutational analysis of the 22 genes encompassing the presumed pUC11B conjugation cluster revealed the presence of several genes with essential conjugation functions, as well as a gene, trsR, encoding a putative transcriptional repressor of this conjugation cluster. Furthermore, plasmid pUC11B encodes an anti-restriction protein, TrsAR, which facilitates higher conjugation frequencies when pUC11B is transferred into recipient strains containing Type II or Type III RM systems. These findings demonstrate how RM mechanisms can be circumvented when they act as a biological barrier for conjugation events.

Safety and efficacy of fractional CO2 laser treatment to the vestibule: a randomized, double-blind, sham-controlled, prospective 3-site clinical study in women with vestibular pain.

BACKGROUND: Data are limited regarding fractional CO2 laser as a nonhormonal treatment for vestibular pain. AIM: We sought to perform what is, to our knowledge, the first multisite prospective randomized, double-blind, sham-controlled clinical trial to assess the safety and efficacy of fractional CO2 laser treatment to the vestibule in women with vestibular pain. METHODS: Subjects (n = 70) meeting inclusion/exclusion criteria at each of 3 sites were randomized 2:1 to active or sham (zero energy) fractional CO2 laser treatment using the vestibular probe (SmartXide2 V2LR - MonaLisa Touch, DEKA, Florence, Italy). Subjects in each treatment arm received 3 treatments 4 weeks apart. At the initial follow-up (week 12), subjects were unblinded and those initially assigned to sham started active treatment. OUTCOMES: Outcome measures included changes from baseline in sexual activity diaries and scores for the Vulvoscopic Genital Tissue Appearance Scale (VGTA), vestibular cotton-tipped swab testing, McGill Pain Questionnaire, Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and the O'Leary-Sant voiding and pain indices, the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI). RESULTS: After active treatment, VGTA scores significantly improved in 5 parameters. Pain associated with cotton-tipped swab testing was significantly reduced at weeks 4 through 16 (mean change from baseline -0.64 [95% CI, -0.79 to -0.50] and -1.31 [95% CI, -1.46 to -1.16], respectively). FSFI pain domain scores improved significantly at weeks 12 and 16 (mean change from baseline 0.925 [95% CI, 0.10-1.75] and 1.22 [95% CI, 0.40-2.05], respectively). FSFI total scores increased significantly at weeks 12 and 16 (mean change from baseline 6.24 [95% CI, 2.64-9.85] and 4.96 [95% CI, 1.36-8.57], respectively). FSDS-R scores decreased significantly at weeks 12 and 16 (mean change from baseline -5.84 [95% CI, -8.80 to -2.87] and -9.15 [95% CI, -12.11 to -6.18], respectively). ICSI scores decreased significantly at weeks 12 and 16 (mean change from baseline -0.91 [95% CI, -1.65 to -0.18] and -0.754 [95% CI, -1.49 to -0.02], respectively). ICPI scores decreased significantly at week 16 (mean change from baseline -0.99 [95% CI, -1.63 to -0.34]). In contrast, there were no significant changes in outcomes in the sham arm. No serious adverse events occurred. CLINICAL IMPLICATIONS: Fractional CO2 laser treatment in women with vestibular pain resulted in improvement from baseline in multiple key outcome measures of vestibular health. STRENGTHS AND LIMITATIONS: Strengths of the study were that it was a multisite prospective randomized double-blind, sham-controlled clinical trial that included multiple measures related to vestibular pain and sexual function. Limitations were the nonvalidated primary outcome measure and limited study cohort. CONCLUSION: Fractional CO2 laser therapy is a safe and effective nonhormonal treatment for vestibular pain.

Lumbar endoscopic spine surgery for persistent genital arousal disorder/genitopelvic dysesthesia resulting from lumbosacral annular tear-induced sacral radiculopathy.

BACKGROUND: Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is characterized by distressing, abnormal genitopelvic sensations, especially unwanted arousal. In a subgroup of patients with PGAD/GPD, cauda equina Tarlov cyst-induced sacral radiculopathy has been reported to trigger the disorder. In our evaluation of lumbosacral magnetic resonance images in patients with PGAD/GPD and suspected sacral radiculopathy, some had no Tarlov cysts but showed lumbosacral disc annular tear pathology. AIM: The aims were 2-fold: (1) to utilize a novel multidisciplinary step-care management algorithm designed to identify a subgroup of patients with PGAD/GPD and lumbosacral annular tear-induced sacral radiculopathy who could benefit from lumbar endoscopic spine surgery (LESS) and (2) to evaluate long-term safety and efficacy of LESS. METHODS: Clinical data were collected on patients with PGAD/GPD who underwent LESS between 2016 and 2020 with at least 1-year follow-up. LESS was indicated because all had lumbosacral annular tear-induced sacral radiculopathy confirmed by our multidisciplinary management algorithm that included the following: step A, a detailed psychosocial and medical history; step B, noninvasive assessments for sacral radiculopathy; step C, targeted diagnostic transforaminal epidural spinal injections resulting in a temporary, clinically significant reduction of PGAD/GPD symptoms; and step D, surgical intervention with LESS and postoperative follow-up. OUTCOMES: Treatment outcome was based on the validated Patient Global Impression of Improvement, measured at postoperative intervals. RESULTS: Our cohort included 15 cisgendered women and 5 cisgendered men (mean ± SD age, 40.3 ± 16.8 years) with PGAD/GPD who fulfilled the criteria of lumbosacral annular tear-induced sacral radiculopathy based on our multidisciplinary management algorithm. Patients were followed for an average of 20 months (range, 12-37) post-LESS. Lumbosacral annular tear pathology was identified at multiple levels, the most common being L4-L5 and L5-S1. Twenty-two LESS procedures were performed in 20 patients. Overall, 80% (16/20) reported improvement on the Patient Global Impression of Improvement; 65% (13/20) reported improvement as much better or very much better. All patients were discharged the same day. There were no surgical complications. CLINICAL IMPLICATIONS: Among the many recognized triggers for PGAD/GPD, this subgroup exhibited lumbosacral annular tear-induced sacral radiculopathy and experienced long-term alleviation of symptoms by LESS. STRENGTHS AND LIMITATIONS: Strengths include long-term post-surgical follow-up and demonstration that LESS effectively treats patients with PGAD/GPD who have lumbosacral annular tear-induced sacral radiculopathy, as established by a multidisciplinary step-care management algorithm. Limitations include the small study cohort and the unavailability of a clinical measure specific for PGAD/GPD. CONCLUSION: LESS is safe and effective in treating patients with PGAD/GPD who are diagnosed with lumbosacral annular tear-induced sacral radiculopathy.