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Sacral squamous cell carcinoma is an uncommon condition that may arise in scars following burns or in chronic wounds, such as an untreated pilonidal cyst. The aim of the present technical note is to describe a surgical technique aimed at minimizing local recurrence rates by en-bloc resection as well as providing immediate plastic reconstruction: 1. right-sided extended vertical rectus abdominis myo-cutaneous (VRAM) flap; 2. abdomino-perineal excision of the rectum with end colostomy; 3. en-bloc excision of the mass inclusive of gluteus maximus muscles and distal sacrectomy; 4. sacrectomy defect covered with VRAM flap; 5. bilateral gluteal defects covered with single-layer dermal substitute of bovine collagen and elastin hydrolysate followed by immediate split-thickness skin grafting from bilateral thigh donor sites, and negative pressure wound therapy dressings. This approach resulted in a favorable outcome at 2-year follow-up in a male patient presenting with a large locally advanced sacral squamous cell carcinoma involving the external anal sphincter muscle.

High-efficacy disease-modifying therapies have been proven to slow disability accrual in adults with relapsing–remitting multiple sclerosis. However, their impact on disability worsening in paediatric-onset multiple sclerosis, particularly during the early phases, is not well understood. We evaluated how high-efficacy therapies influence transitions across five disability states, ranging from minimal disability to gait impairment and secondary progressive multiple sclerosis, in people with paediatric-onset multiple sclerosis.

The aim of this pooled analysis was to evaluate the impact of robotic total mesorectal excision (TME) on pathology metrics in Male Overweight patients with Low rectal cancer (MOL). This was a multicenter retrospective pooled analysis of data. Two groups were defined: MOL (Male, Overweight, Low rectal cancer) and non-MOL. Overweight was defined as BMI ≥ 25 kg/m2. Low rectal cancer was defined as cancer within 6 cm from the anal verge. The primary endpoints of this study were histopathological metrics, namely circumferential resection margin (CRM) (mm), CRM involvement rate (%), and the quality of TME. Circumferential resection margin (CRM) was involved if < 1 mm. 836 (106 MOL and 730 non-MOL) patients that underwent robotic TME by six surgeons over 3 years were compared. No significant differences in demographics and perioperative variables were found, except for operating time, distal margin, and number of lymph nodes harvested. CRM involvement rate did not significantly differ (7.5% vs. 5.5%, p= 0.395). Mean CRM was statistically significantly narrower in MOL patients (6.6 vs. 7.7 mm, p= 0.04). Quality of TME did not differ. Distance of tumor from the anal verge was the only independent predictor of CRM involvement. Robotic TME may provide optimal pathology metrics in overweight males with low rectal cancer. Although CRM was a few millimeters narrower in MOL, the values were within the range of uninvolved margins making the difference statistically significant, but not clinically. Being MOL was not a risk factor for involvement of circumferential resection margin.

Abstract: Purpose: This study was designed to evaluate the impact of a standardized laparoscopic intracorporeal right colectomy on the short-term outcome of patients with neoplasia. Methods: Consecutive patients with histologically proven right colon neoplasia underwent a standardized laparoscopic intracorporeal right colectomy with medial to lateral approach encompassing ten sequential steps: 1) ligation of ileocolic vessels, 2) identification of right ureter, 3) dissection along superior mesenteric vein, 4) division of omentum, 5) division of right branch of middle colic vessels, 6) transection of transverse colon, 7) mobilization of right colon, 8) transection of terminal ileum, 9) ileocolic anastomosis, 10) delivery of specimen. Values were medians (ranges). Results: From July 2002 to June 2005, 111 laparoscopic intracorporeal right colectomies were attempted with a 5.4 percent conversion rate. There were 57 women and 54 men, aged 64.9 (range, 40–85) years, with body mass index of 33 (range, 20–43), American Society of Anesthesiology score of 2 (range, 2–4), 36.9 percent comorbidities, and 37.8 percent previous abdominal surgery. The indication for surgery was cancer in 109 patients. Operative time was 120 (range, 80–185) minutes. Estimated blood loss was 69 (range, 50–600) ml. Overall length of skin incisions was 66 (range, 60–66) mm; 29 (range, 2–41) lymph nodes were harvested. Length of stay was four (range, 2–30) days. Complication rate was 4.5 percent. Conclusions: A standardized laparoscopic intracorporeal right colectomy resulted in a favorable short-term outcome in unselected patients with neoplasia of the right colon.

IMPORTANCE: Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair. OBJECTIVE: To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS). DESIGN, SETTING, AND PARTICIPANTS: This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register. MAIN OUTCOMES AND MEASURES: The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors. EXPOSURES: Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT. RESULTS: After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) (P &lt; .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P &lt; .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P &lt; .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P &lt; .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001). CONCLUSIONS AND RELEVANCE: PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study’s findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.

Abstract: Purpose: This study was performed to compare open Hartmann’s reversal to laparoscopic Hartmann’s reversal with regard to complication, readmission, and reoperation rates. Methods: Data of patients who underwent open Hartmann’s reversal or laparoscopic Hartmann’s reversal between 1998 and 2004 at two institutions were collected. End points were complications in the hospital or after discharge, readmission to the hospital, and reoperation within 6 months after initial surgery. Results: Sixty-one open Hartmann’s reversal and 61 laparoscopic Hartmann’s reversal patients were well matched except for American Society of Anesthesiology grade (1.9 vs. 1.6; P = 0.008), timing of Hartmann’s procedure (14 vs. 6 months; P = 0.001), operation time (210 vs. 154 minutes; P = 0.001), and estimated blood loss (363 vs. 254ml; P = 0.01). Thirty-day complication rates did not differ (18 vs. 13 percent). At 6 month follow-up, open Hartmann’s reversal patients had increased complication (16.4 vs. 3.3 percent; P = 0.015) and reoperation (13.1 vs. 3.3 percent; P = 0.048) rates but the same readmission rates (16.4 percent). Conclusions: Compared with open Hartmann’s reversal, 6 month complication and reoperation rates were lower in laparoscopic Hartmann’s reversal patients. Most of the six-month complications and reoperations in open Hartmann’s reversal were abdominal wall-related. Readmission rates were similar, but reasons for readmission were surgical in open Hartmann’s reversal and medical in laparoscopic Hartmann’s reversal.

Antenatal exposures to maternal stress and to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) have been independently associated with developmental outcomes in early infancy and beyond. Knowledge about their joint impact, biological mechanisms of their effects and timing-effects, is still limited. Both PM2.5and maternal stress exposure during pregnancy might result in altered patterns of DNA methylation in specific stress-related genes, such as the serotonin transporter gene (SLC6A4 DNAm), that might, in turn, influence infant development across several domains, including bio-behavioral, cognitive and socio-emotional domains. Here, we investigated the independent and interactive influence of variations in antenatal exposures to maternal pandemic-related stress (PRS) and PM2.5on SLC6A4 DNAmlevels in newborns. Mother–infant dyads (N= 307) were enrolled at delivery during the COVID-19 pandemic. Infants’ methylation status was assessed in 13 CpG sites within the SLC6A4gene’s region (chr17:28562750–28562958) in buccal cells at birth and women retrospectively report on PRS. PM2.5exposure throughout the entire gestation and at each gestational trimester was estimated using a spatiotemporal model based on residential address. Among several potentially confounding socio-demographic and health-related factors, infant’s sex was significantly associated with infants’ SLC6A4 DNAm levels, thus hierarchical regression models were adjusted for infant’s sex. Higher levels of SLC6A4 DNAmat 6 CpG sites were found in newborns born to mothers reporting higher levels of antenatal PRS and greater PM2.5exposure across gestation, while adjusting for infant’s sex. These effects were especially evident when exposure to elevated PM2.5occurred during the second trimester of pregnancy. Several important brain processes (e.g., synaptogenesis and myelination) occur during mid-pregnancy, potentially making the second trimester a sensitive time window for the effects of stress-related exposures. Understanding the interplay between environmental and individual-level stressors has important implications for the improvement of mother-infant health during and after the pandemic.

The aim of this study was to evaluate whether the mesorectal fat area (MFA) has an impact on the histopathology metrics of the specimen in male patients undergoing robotic total mesorectal excision (rTME) for cancer in the distal third of the rectum. Prospectively collected data of patients undergoing rTME for resectable rectal cancer by five surgeons during 3 years were extracted from the REgistry of Robotic SURgery for RECTal cancer (RESURRECT). MFA was measured at preoperative MRI. Distal rectal cancer was defined as within 6 cm from the anal verge. Specimen metrics included circumferential resection margin (CRM) measured by pathologists as involved if < 1 mm, distal resection margin (DRM) and TME quality. Of 890 patients who underwent rTME for rectal cancer, a subgroup analysis compared 116/581 (33.4%) with MFA > 20 cm2to 231/581 (66.6%) with MFA ≤ 20 cm2. The mean CRM in patients with MFA > 20 cm2was neither statistically nor clinically significantly different from patients with MFA ≤ 20 m2(6.8 ± 5.6 mm vs. 6.0 ± 7.5 mm; p= 0.544). The quality of TME did not significantly differ: complete TME 84.3% vs. 80.3%; nearly complete TME 12.9% vs. 10.1%; incomplete TME 6.8% vs. 5.6%. The DRM was not significantly different: 1.9 ± 1.9 cm vs. 1.9 ± 2.5 cm; p= 0.847. In addition, the intraoperative complication rate was not significantly different: 4.3% (n= 5) vs.2.2% (n= 5) (p= 0.314). This prospective multicenter study did not find any evidence to support that larger MFA would result in poorer histopathology metrics of the specimen when performing rTME in male patients with distal rectal cancer.

Background Hartmann’s reversal (HR) is associated with significant technical complexity and morbidity. The decision to perform HR is difficult and up to 50% of patients with colostomies do not undergo a reversal. To better guide surgeons and patients with this decision, we sought to assess the surgical risks and outcomes of HR as compared to elective left colectomy (LC).Methods We conducted a retrospective analysis of a prospective database at a tertiary medical center. Patients undergoing elective Hartmann’s reversal and left colectomy between January 2014 and November 2021 were identified. We compared preoperative variables, intraoperative events, and short-term postoperative outcomes.Results 135 patients were identified: 30 HR and 105 LC. There were no significant differences in demographics or preoperative comorbidities between HR and LC. There were more open and fewer robotic cases in HR (23.3% vs 2.9%, P< .0001; 46.6% vs 76.0%, P< .01). Total operative time was significantly longer in HR than LC (261.8 vs 211.7 minutes, P= .02). There was a significantly higher percentage of intraoperative complications in HR (13.3% vs 1.9%, P< .01). There was a significantly higher rate of minor postoperative complications in HR than LC (46.7% vs 26.7%, P= .04), but not major (6.7% vs 5.8%, P= .85). Time to first flatus/bowel movement was significantly longer in HR than LC (3.6 vs 2.5 days, P< .001).Conclusion Hartmann’s reversal is a more technically challenging operation than elective left colectomy and is associated with significantly higher rates of intraoperative and minor postoperative complications. Future studies should focus on mitigating these risk factors to optimize patient outcomes.

BackgroundSome studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS.MethodsWe compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS.ResultsIncluded patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2–47.3) vs 43.9 (43.3–44.4); p<0.001), greater baseline disability, slower disability accrual (HR 0.86 (0.78–0.94); p<0.001) and similar age at wheelchair dependence.ConclusionsWe demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials.

There is currently no standardized robotic surgery training program in General Surgery Residency. RAST involves three modules: ergonomics, psychomotor, and procedural. This study aimed to report the results of module 1, which assessed the responsiveness of 27 PGY (postgraduate year) 1–5 general surgery residents (GSRs) to simulated patient cart docking, and to evaluate the residents’ perception of the educational environment from 2021 to 2022. GSRs prepared with pre-training educational video and multiple-choice questions test (MCQs). Faculty provided one-on-one resident hands-on training and testing. Nine proficiency criteria (deploy cart; boom control; driving cart; docking camera port; targeting anatomy; flex joints; clearance joints; port nozzles; emergency undocking) were assessed with five-point Likert scale. A validated 50-item Dundee Ready Educational Environment Measure (DREEM) inventory was used by GSRs to assess the educational environment. Mean MCQ scores: (90.6 ± 16.1 PGY1), (80.2 ± 18.1PGY2), (91.7 ± 16.5 PGY3) and (PGY4, 86.8 ± 18.1 PGY5) (ANOVA test; p= 0.885). Hands-on docking time decreased at testing when compared to base line: median 17.5 (range 15–20) min vs. 9.5 (range 8–11). Mean hands-on testing score was 4.75 ± 0.29 PGY1; 5.0 ± 0 PGY2 and PGY3, 4.78 ± 0.13 PGY4, and 4.93 ± 0.1 PGY5 (ANOVA test; p= 0.095). No correlation was found between pre-course MCQ score and hands-on training score (Pearson correlation coefficient = − 0.359; p= 0.066). There was no difference in the hands-on scores stratified by PGY. The overall DREEM score was 167.1 ± 16.9 with CAC = 0.908 (excellent internal consistency). Patient cart training impacted the responsiveness of GSRs with 54% docking time reduction and no differences in hands-on testing scores among PGYs with a highly positive perception.

BackgroundSimultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years.MethodsData from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement.Results23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability.ConclusionsThe effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjsurg.2006.01.030 Byline: Giuseppe DiGiuro (a), Dejan Ignjatovic (a), Jan Brogger (a), Roberto Bergamaschi (a) Keywords: Rectal prolapse; Recurrence; Re-operation; Surgery; Actuarial analysis Abstract: The literature shows wide variations of recurrence rates (RRs) after abdominal surgery for rectal prolapse. The aim of this meta-analysis was to evaluate the accuracy of published RRs. Author Affiliation: (a) Department of Research and Development, Forde Health System, Forde, Norway 6807 Article History: Received 26 October 2005; Revised 15 January 2006

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjsurg.2005.03.021 Byline: Miroslav Uchal, Jostein Tjugum, Egil Martinsen, Xinguang Qiu, Roberto Bergamaschi Abstract: To compare the impact of sleep deprivation after 24-hour duty (post-call) with that of 8-hour work (post-work) on product quality (PQ) and procedure effectiveness (PE) in a laparoscopic physical simulator. Author Affiliation: Department of Research and Development, Forde Health System, University of Bergen, Forde 6807, Norway

•Disease-modifying therapies prescriptions in multiple sclerosis changed over time.•The Italian register provides spatial and temporal data about such prescriptions.•High effective therapies prescriptions increased since 2000s in Italy.•No spatial differences are observed across Italian geographic areas.•This trend could be due to prescribers’ practice and patients’ preferences.

In the pain management evolution, opioid-free analgesia and multimodal analgesia strategies have emerged as feasible in many surgical settings including colorectal surgery. This was a retrospective cohort study including patients having undergone elective bowel resection between February 2012 and June 2018 aiming to evaluate whether there was reduction in opioid use after implementation of opioid-free analgesia in one medical centre. Trend analysis was conducted using Joinpoint regression employing nine-month intervals. The primary outcome for each interval was the proportion of patients receiving postoperative opioid-free analgesia, defined as forgoing all opioid analgesics after the day of surgery. This study showed a significant increasing trend in opioid-free analgesia in elective bowel resection from 0 to 42.5% over 4.5 years.

IMPORTANCE: It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS). OBJECTIVE: To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation. DESIGN, SETTING, AND PARTICIPANTS: In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018. Among 53 680 patients in the MSBase registry, 4997 patients with SPMS (using the Lorscheider definition) were identified. Of those, 1621 patients were eligible for study inclusion based on sufficient follow-up before and after the onset of SPMS. Data were analyzed from November 15, 2017, to January 13, 2020. EXPOSURES: The association between disability accumulation and several clinical and demographic variables, including relapses and exposure to immunotherapy, was evaluated. MAIN OUTCOMES AND MEASURES: Two outcomes were analyzed as measures of disability accumulation during SPMS: the rate of disability accumulation during the secondary progressive phase (change relative to the reference population of patients with MS and absolute change) and the risk of becoming wheelchair dependent. A third outcome, the cumulative risk of experiencing confirmed disability progression events, was used for a secondary analysis. Outcomes were evaluated using multivariable mixed models (ie, linear and Cox models). RESULTS: Of 1621 patients eligible for inclusion, 1103 patients (68.0%) were female, with a mean (SD) age at MS onset of 33.9 (10.6) years. A total of 661 patients (40.8%) experienced superimposed relapses during SPMS. Therapy receipt and relapses during early relapsing-remitting MS were not associated with disability accumulation during the secondary progressive phase. Higher relapse rates during the secondary progressive disease stage were associated with an increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P = .009). Among patients who experienced superimposed relapses during SPMS, greater receipt of disease-modifying therapies was significantly associated with a reduced rate of disability progression and a lower risk of becoming wheelchair dependent. CONCLUSIONS AND RELEVANCE: In this study, the rate of disability progression after the onset of SPMS was not associated with the early disease course and treatment decisions. Relapses during SPMS were associated with accelerated disability progression and represent an accessible treatment target. Disease-modifying therapy was associated with improvements in disability outcomes among patients with active relapses during SPMS. The study’s results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS.

A beneficial impact of robotic proctectomy on circumferential resection margin (CRM) is expected due to the robot's articulating instruments in the pelvis. There are however concerns about a negative impact on the quality of total mesorectal excision (TME) due to the lack of tactile feedback. The aim of this study was to assess whether surgeons' learning curve impacted CRM and TME quality.

Supplemental Digital Content is available in the text.

The aim of this meta-analysis was to determine whether transanal total mesorectal excision (taTME) improves histopathology metrics and/or complication rates when compared to robotic total mesorectal excision (R-TME) of resectable rectal cancer.

ObjectiveOral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.MethodsWe identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).ResultsThe eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).ConclusionThe effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.

We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology. This study presents OncoTreat, a framework for the prioritization of compounds targeting mechanistic tumor dependencies in individual patients.

ObjectiveTo evaluate variability and predictability of disability trajectories in moderately advanced and advanced multiple sclerosis (MS), and their modifiability with immunomodulatory therapy.MethodsThe epochs between Expanded Disability Status Scale (EDSS) steps 3–6, 4–6 and 6–6.5 were analysed. Patients with relapse-onset MS and having reached 6-month confirmed baseline EDSS step (3/4/6) were identified in MSBase, a global observational MS cohort study. We used multivariable survival models to examine the impact of disease-modifying therapy, clinical and demographic factors on progression to the outcome EDSS step (6/6.5). Sensitivity analyses with varying outcome definitions and inclusion criteria were conducted.ResultsFor the EDSS 3–6, 4–6 and 6–6.5 epochs, 1560, 1504 and 1231 patients were identified, respectively. Disability trajectories showed large coefficients of variance prebaseline (0.92–1.11) and postbaseline (2.15–2.50), with no significant correlations. The probability of reaching the outcome step was not associated with prebaseline variables, but was increased by higher relapse rates during each epoch (HRs 1.58–3.07; p<0.001). A greater proportion of each epoch treated with higher efficacy therapies was associated with lower risk of reaching the outcome disability step (HRs 0.72–0.91 per 25%; p≤0.02). 3 sensitivity analyses confirmed these results.ConclusionsDisease progression during moderately advanced and advanced MS is highly variable and amnesic to prior disease activity. Lower relapse rates and greater time on higher efficacy immunomodulatory therapy after reaching EDSS steps 3, 4 and 6 are associated with a decreased risk of accumulating further disability. Highly effective immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced relapse-onset MS.

The authors studied close to one thousand diagnosed cases of cancer of the colon or rectum (colorectal carcinoma). Two percent had cancers of the colon and rectum simultaneously. These patients also had a higher occurrence of noncancerous (benign) tumors than other subjects. Patients with simultaneous tumors were more likely to have effected lymph nodes. The microscopic appearance of the glandular tumors was mucous-like. The five-year survival rate for the patients with simultaneous cancers was not different from individuals afflicted by a single cancer. Barium enema x-ray studies were found to be inconclusive and colonoscopic (the examination of the entire colon through the use of a fiber optic viewing instrument) was the preferred diagnostic method adopted. The authors suggest a conservative surgical approach.

•PM2.5, PM10 and NO2 are risk factors for Covid-19 pneumonia among MS patients.•We studied the joint exposure to the three pollutants as an environmental mixture.•The most dangerous pollutants within the mixture were NO2 and PM2.5.

•PBMCs from people with MS (PwMS) have lower HuR than healthy controls (HC).•PBMCs from PwMS have a lower MnSOD protein content compared to HC.•SOD2mRNA is a new target of HuR protein.•In PBMCs from PwMS one year of dimethyl fumarate restores HuR and MnSOD protein content to the HC's levels.

•Bilateral coordination of gait was assessed at self-selected and fast speeds in MS.•Accuracy, variability & bilateral coordination of gait were enhanced at fast speed.•Stride frequency, stance and swing durations are related to disease severity.•Bilateral coordination of gait was moderately related to disease severity and age.

•The aim of this study was to construct such score and to evaluate its performance.•3852 patients were included in the study and 17% of the patients required hospitalization.•This score can be used as an additional instrument to identify high-risk patients and persuade them to take important measures to prevent Covid-19 infection.

AbstractThe radiation-induced injury to normal tissue is a well-described phenomenon that incites tissue hypoxia, vascular damage, and parenchymal cell death. In addition to the morbidity caused by the radiation-induced injury itself, surgical management adds to the overall morbidity in these patients. We herein present a case demonstrating challenges of surgical management of urological complications in a radiated pelvis including delayed bladder perforation, recurrence of vesicovaginal fistula, and ureteral stricture. Nonoperative management strategies should be exhausted prior to surgical intervention.

This study was performed to evaluate short-term clinical outcomes of laparoscopic intracorporeal ileocolic anastomosis following resection of the right colon.This was a retrospective study of selected patients who underwent laparoscopic intracorporeal ileocolic anastomosis following resection of the right colon for tumors or Crohn’s disease by a single surgeon from July 2002 through June 2012. Data were retrieved from an Institutional Review Board-approved database. Study end point was postoperative adverse events, including mortality, complications, reoperations, and readmissions at 30 days. Antiperistaltic side-to-side anastomoses were fashioned laparoscopically with a 60-mm-long stapler cartridge and enterocolotomy was hand-sewn intracorporeally in two layers. Values were expressed as medians (ranges) for continuous variables.There were 243 patients (143 females) aged 61 (range = 19–96) years, with body mass index of 29 (18–43) kg/m2and ASA 1:2:3:4 of 52:110:77:4; 30 % had previous abdominal surgery and 38 % had a preexisting comorbidity. There were 84 ileocolic resections with ileo ascending anastomosis and 159 right colectomies with ileotransverse anastomosis. Operating time was 135 (60–220) min. Estimated blood loss was 50 (10–600) ml. Specimen extraction site incision length was 4.1 (3–4.4) cm. Conversion rate was 3 % and there was no mortality at 30 days, 15 complications (6.2 %), and 8 reoperations (3.3 %). Readmission rate was 8.7 %. Length of stay was 4 (2–32) days. Pathology confirmed Crohn’s disease in 84 patients, adenocarcinoma in 152, and other tumors in 7 patients.Laparoscopic intracorporeal ileocolic anastomosis following resection of the right colon resulted in a favorable outcome in selected patients with Crohn’s disease or tumors of the right colon.

Postinfectious neurologic syndromes (PINSs) of the CNS include heterogeneous disorders, sometimes relapsing. In this study, we aimed to a) describe the spectrum of PINSs; b) define predictors of outcome in PINSs; and c) assess the clinicalparaclinical features that help differentiate PINSs from multiple sclerosis (MS).

Abstract: Background: The validity of current animal colon cancer models is questionable. This study was performed to evaluate whether colonoscopic injection of a murine colon cancer cell line into the cecal wall of immunocompetent rats leads to a solid tumor. Methods: A bolus of bowel prep was given to BD-IX rats. Anesthesia was injected intraperitoneally. Video fiberscope allowed for irrigation and suction. Failure was inability to reach/inject cecum. Procedure was performed by four surgeons; 100 μl of colon tumor cell suspension (DHD/K12TRb; 10 million cells in 0.1 ml) was injected into cecal wall with 23-gauge needle placed on 3 mm wire resulting in a blister. Rats were allowed to recover. Solid tumor growth was measured at scheduled necropsy at 4 weeks. Sample size (107 rats: type I error 0.05; power 80%) was based on a pilot study. Data were presented as median (range). Results: A total of 107 male BD-IX retired breeders weighing 356 g (range 256–432 g) underwent colonoscopy with submucosal injection of cecal wall. A single solid cecal cancer was identified in 98 (91.5%) rats at scheduled necropsy. Histology confirmed adenocarcinoma with tumor size of 4 mm (range 2.6–8.4 mm). Peritoneal carcinomatosis was found in ten (9.3%) rats. Distant metastases were found in three (2.8%) rats. Complications occurred in four (3.8%) rats: two aspirations and two colon perforations. Conclusions: A solid cecal tumor without carcinomatosis or metastasis has been developed by colonoscopic injection of a rat colon cancer cell line in 79% of immunocompetent rats.

Abstract: Background: The short-term results of the Sigma trial show that laparoscopic sigmoid resection (LSR) used electively for diverticular disease offers advantages over open sigmoid resection (OSR). This study aimed to compare the overall mortality and morbidity rates after evaluation of the clinical outcomes at the 6-month follow-up evaluation. Methods: In a prospective, multicenter, double-blind, parallel-arm, randomized control trial, eligible patients were randomized to either LSR or OSR. The short-term results and methodologic details have been published previously. Follow-up evaluation was performed at the outpatient clinic 6 weeks and 6 months after surgery. Results: In this trial, 104 patients were randomized for either LSR or OSR, and the conversion rate was 19.2%. The LSR approach was associated with short-term benefits such as a 15.4% reduction in the major complications rate, less pain, and a shorter hospital stay at the cost of a longer operating time. At the 6-month follow-up evaluation, no significant differences in morbidity or mortality rates were found. Two patients died of cardiac causes (overall mortality, 3%). Late complications (7 LSR vs. 12 OSR; p = 0.205) consisted of three incisional hernias, five small bowel obstructions, four enterocutaneous fistulas, one intraabdominal abscess, one retained gauze, two anastomotic strictures, and three recurrent episodes of diverticulitis. Nine of these patients underwent additional surgical interventions. Consideration of the major morbidity over the total follow-up period (0–6 months) shows that the LSR patients experienced significantly fewer complications than the OSR patients (9 LSR vs. 23 OSR; p = 0.003). The Short Form-36 (SF-36) questionnaire showed significantly better quality of life for LSR at the 6-week follow-up assessment. However, at the 6-month follow-up assessment, these differences were decreased. Conclusions: The late clinical outcomes did not differ between LSR and OSR during the 30-day to 6-month follow-up period. Consideration of total postoperative morbidity shows a 27% reduction in major morbidity for patients undergoing laparoscopic surgery for diverticular disease.

No randomized controlled trial has compared no rectopexy with rectopexy for external full-thickness rectal prolapse.