Early Symptomatic Improvement Research Articles

Perioperative Segmentation of the Posterior Fossa and the Keel of Goodrich in Surgical Outcomes of Chiari Malformations

BackgroundChiari I malformation (CM- I) is defined as the extension of brain tissue into the spinal cord. This study aimed to refine the methodology for the acquisition of 3-dimensional measurements of the posterior fossa and introduce occipital keel size as a new marker and its impact in patients with CM. Materials and MethodsIn this retrospective study, all patients who underwent Chiari decompression surgery at Montefiore Medical Center from April 2012 to April 2022 were included. Perioperative clinical information was obtained in addition to maximal keel thickness (KT), foramen magnum area, and pre-and postoperative posterior fossa volumes for each patient and age-matched controls. Volumetric measurements were obtained using AI-based semiautomated segmentation. ResultsA total of 107 patients with CM including 37 males, and 70 females were studied with a mean age of 26.56±17.31 compared with 103 controls without CM. The comparison between the CM and the general population groups demonstrated a significantly increased keel size in Chiari patients. Keel size had a significant relationship with dysphagia, paresthesia, and intraoperative blood loss, while posterior volume change had a significant relationship with sex and early symptomatic improvement. The Foramen magnum area was related to tonsillar descent and more prominent in patients with spina bifida. ConclusionThe Keel of Goodrich is a new anatomical factor that should be taken into consideration when evaluating preoperative symptoms, and intraoperative complications in patients with CM-1. Volumetric analyses demonstrated that posterior fossa volume change had a significant impact on early symptom improvement in patients with Chiari, as did the choice of operative approach. The routine use of semi-automated segmentation of the posterior fossa may help stratify Chiari patients in the future and should be implemented in routine clinical care.

When to hold and when to fold: Early prediction of nonresponse to transcranial magnetic stimulation in major depressive disorder

BackgroundDetermining when to recommend a change in treatment regimen due to insufficient improvement is a common challenge in therapeutics. MethodsIn a sample of 7215 patients with major depressive disorder treated with transcranial magnetic stimulation (TMS) and with PHQ-9 scores before, during and after the course, 3 groups were identified based on number of acute course sessions: exactly 36 sessions (N = 3591), more than 36 sessions (N = 975), and less than 36 sessions (N = 2649). Two techniques were used to determine thresholds for percentage change in PHQ-9 scores at assessments after 10, 20, and 30 sessions that optimized prediction of endpoint response status: the Youden index and fixing the false positive rate at 10%. Positive and negative predictive values were calculated to assess the accuracy of identifying final nonresponders and responders, respectively. ResultsThere was greater accuracy in predicting final response than nonresponse, especially in the groups that had at least 36 sessions. Substantial proportions of patients with low levels of early improvement were classified as responders at the end of treatment. LimitationsThe findings should be validated with clinician ratings using a more comprehensive depression severity scale. ConclusionsManifesting clinical improvement early in the TMS course is strongly predictive of final status as a responder, while lack of early improvement is a relatively poor indicator of final nonresponse status. The predictive value of lack of early symptomatic improvement is too low to make reliable recommendations regarding changes in treatment regimen.

S844 Early Symptomatic Improvement With Guselkumab Induction Treatment in Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 QUASAR Induction Study

S844 Early Symptomatic Improvement With Guselkumab Induction Treatment in Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 QUASAR Induction Study

Prospective Comparative Short-Term Study of Autologous Leucocyte-Rich Platelet-Rich Plasma vs. Local Steroids in Chronic Plantar Fascitis

Background Plantar fasciitis is the most common cause of heel pain and is difficult to treat in most chronic and severe forms. Management of plantar fasciitis includes non-surgical options such as non-steroidal anti-inflammatory drugs and corticosteroids, physical therapy, orthotics, and surgical management includes plantar fasciotomy. Local injection of platelet-rich plasma as well as local steroids is an emerging concept in treating recalcitrant tendon and ligament pathology, including plantar fasciitis. Objectives The aim of the study was to evaluate and compare the outcome of patients treated with a single injection of autologous leucocyte-rich platelet-rich plasma with single-injection local steroids triamcinolone in chronic plantar fasciitis. Methodology The study was conducted for a duration of 24 months. In total, 60 patients with clinically diagnosed chronic plantar fasciitis were selected for study and divided in two groups using the single allocation randomization method as those treated with autologous injection leucocyte-rich platelet-rich plasma and those with injection local steroid triamcinolone and prospectively followed and compared. Results Both groups were evaluated subjectively and functionally at primary visit and then on follow-up at 2 weeks, 4 weeks, 8 weeks, and 12 weeks by VAS and hind foot AOFAS score. Conclusion We concluded that both injection platelet-rich plasma-treated and injection local steroid-treated patients provide symptomatic relief in the treatment of chronic plantar fasciitis both subjectively and functionally. The steroid treated group showed early symptomatic improvement at 2 weeks, and results at 12 weeks to further follow-up were suggestive that single-injection leucocyte-rich platelet-rich plasma provided better functional results.

DOP38 Upadacitinib Therapy Reduces Crohn’s Disease Symptoms Within the First Week of Induction Therapy

Abstract Background Upadacitinib (UPA), an oral, selective JAK inhibitor demonstrated superior efficacy for clinical remission compared with placebo (PBO) and an acceptable safety profile in patients with moderately to severely active Crohn’s disease (CD) in 2 phase 3 induction trials, U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836).1-2 There remains an unmet need for therapies that provide rapid symptom relief in ambulatory patients with moderate to severe CD experiencing disease flares. This sub-analysis evaluated the efficacy of UPA 45 mg once daily (UPA45) on early symptomatic improvement for the first 15 days of treatment, using pooled data from U-EXCEL and U-EXCEED. Methods U-EXCEL and U-EXCEED were multicentre, double-blind, PBO-controlled trials that enrolled patients who had average daily very soft or liquid stool frequency (SF) ≥4 and/or abdominal pain score (APS) ≥2 at baseline, plus a Simple Endoscopic Score for CD ≥6 (≥ 4 for patients with isolated ileal disease), excluding the narrowing component. Patients (n=1021) were randomized (2:1 ratio) to receive UPA45 (n=674) or PBO (n=347) for 12 weeks. First dose of study drug was administered on day 1. Improvement in daily symptoms of SF and APS, in addition to time to first achievement of daily SF/APS clinical remission were assessed. Results Patients treated with UPA45 experienced a significant improvement in daily symptoms compared with PBO-treated patients, simultaneously achieving SF < 3 and APS ≤ 1 beginning at day 3 (9.6% UPA vs. 5.8% PBO) (P≤0.05, Figure 1A). Difference from PBO was maintained through day 15 (P≤0.05), except for day 4 (P=0.0518). Similar results were found when evaluating each symptom separately, with a higher proportion of patients who received UPA45 achieving either SF < 3, beginning at day 5 (31.6% UPA vs. 23.1% PBO, Figure 1B). UPA-treat patients attained significance for APS ≤ 1 beginning at day 6 (49.1% UPA vs. 39.3% PBO, Figure 1C), compared with patients that received PBO. Differences from PBO were sustained through day 15 for either symptom (P≤0.01 for both endpoints). A greater proportion of patients receiving UPA45 also demonstrated at least a 60% decrease in SF by day 5, compared to PBO, which was maintained through day 15 (P≤0.01, Figure 1D). Patients treated with UPA45 achieved daily SF/APS clinical remission significantly earlier than PBO-treated patients (median time to clinical remission: 13 days UPA45 vs 32 days PBO; P<0.0001, Figure 2). Conclusion Patients who received UPA 45 mg once daily significantly improved daily symptoms of diarrhea or abdominal pain within the first week of treatment and achieved daily clinical remission faster than PBO-treated patients, providing rapid symptom relief.

Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment

We evaluated the efficacy of once-daily (QD) upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, on early symptomatic improvement for ulcerative colitis (UC). Post hoc analyses were performed on pooled data from 2 replicate, phase 3, multicenter induction trials, U-ACHIEVE Induction and U-ACCOMPLISH, to determine the earliest time point of efficacy onset. Diary entry data through 14 days from the first dose of placebo or upadacitinib 45 mg QD were analyzed for daily improvement in UC symptoms (stool frequency, rectal bleeding, abdominal pain, and bowel urgency). Changes in inflammatory markers, high-sensitivity C-reactive protein (hs-CRP), and fecal calprotectin (FCP) were assessed at week 2 and quality of life (QoL) at weeks 2 and 8. Regression analysis determined the association between changes in UC symptoms and the likelihood of achieving clinical remission/response per Adapted Mayo score at week8. Overall, 988 patients (n= 328 placebo, n= 660 upadacitinib) were analyzed. Patients treated with upadacitinib demonstrated significant improvements vs placebo in all UC symptoms between days 1 and 3 and maintained through day 14. A >50% reduction from baseline in hs-CRP and FCP levels was achieved by 75.7% and 48.2% of patients, respectively (P < .001 vs placebo). Increased rates of clinical remission/response per Partial Mayo score from week 2 (26.9%/59.4% upadacitinib 45 mg QD vs 4.3%/22.3% placebo, P < .001) and significant improvements in QoL at weeks 2 and 8 were observed. Early improvement in stool frequency and bowel urgency by day 3 and reductions in hs-CRP and FCP by week 2 were significantly associated with clinical remission/response at week8. Upadacitinib 45 mg QD provided rapid relief of UC symptoms from day 1. gov: U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026).

Efficacy of programmed cell death protein 1 (PD1) inhibitors in cutaneous squamous cell carcinoma (cSCC) patients with large nerve-perineural invasion (LN-PNI): A multicenter retrospective study.

e21577 Background: Response rates to PD1 inhibitors are high in unresectable locally advanced or metastatic cSCC. However, the management of cSCC patients with LN-PNI is challenging given that standard measures of disease burden and treatment response are poorly suited to PNI. This study aims to quantify radiological and symptomatic PD1 inhibitor response in cSCC LN-PNI. Methods: Patients with biopsy or radiologically confirmed cSCC LN-PNI treated with PD1 inhibitors between September 2017 and April 2021 were enrolled in this retrospective observational study. Radiological disease control (RDC) was defined as non-progressive radiological changes (including absence of proximal extension of PNI) ± partial or complete resolution on MRI or CT. A detailed symptomatic assessment was performed at every clinic visit. Progression free survival (PFS) was calculated from the time of initiating treatment to radiological disease progression (RDP). Survival was calculated using the Kaplan-Meier method and Cox regression was used to determine the effect of early symptomatic response (≤6 wks) and RDC at first staging scan (≤12 wks) on PFS. Results: Four Australian hospitals enrolled 31 cSCC LN-PNI patients (median age 75 years; M: F = 3:1), of which 29 (93.5%) had trigeminal and 9 (29.0%) had facial nerve involvement. Symptoms were present in 29 (93.5%) patients at baseline, including neuropathic pain in 24 (77.4%) and motor weakness (facial palsy or ophthalmoplegia) in 10 (32%). 16 (51.6%) patients had prior surgery or radiotherapy, but none received prior systemic therapy for LN-PNI. RDC on first restaging (6-12 wks) was observed in 28 (90.3%) patients and symptomatic improvement was seen in 23 (79.3%) amongst the 29 symptomatic at presentation. At a median follow-up of 18.7 months, patients with RDC on first restaging scan had a 24-month PFS of 84.2% versus 25% with RDP (p &lt; 0.001, HR = 0.086, 95% CI = 0.018 to 0.403). Symptomatic response at 6 wks was associated with superior 12-month PFS (94.7% versus 55.6%, p &lt; 0.01, HR = 0.068; 95% CI 0.008 to 0.584). There was high concordance (89.6%) between symptomatic and radiological control (Cohen’s Κ = 0.61, χ2 = 8.0023, p-value = 0.0047). Ocular toxicity was seen in 5 patients (16.1%), with corneal ulceration in 2 patients which was higher than expected but otherwise, toxicity profile was consistent with PD-1 inhibitors. Conclusions: These results demonstrate high response rates of PD1 inhibitors in patients with cSCC LN-PNI with acceptable toxicity and durability of response. Early symptomatic improvement within 6 wks and RDC on the first staging scan were significant markers of durable treatment response. PD1 inhibitors are active in patients with LN-PNI and should be considered for the treatment of cSCC with LN-PNI.

Early Symptomatic Improvement After Ustekinumab Therapy in Patients With Ulcerative Colitis: 16-Week Data From the UNIFI Trial

Rapid symptomatic relief is an important treatment goal for patients with ulcerative colitis (UC). We aimed to characterize early response with ustekinumab in patients with moderate-to-severe UC during the initial 16 weeks of treatment. We performed a post hoc analysis of data from A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis trial. Patients (N= 961) were randomized (1:1:1) to receive intravenous 130 mg ustekinumab, approximately 6 mg/kg ustekinumab, or placebo at week 0. Symptomatic remission, absolute stool number, Mayo stool frequency and rectal bleeding subscores, partial Mayo score, C-reactive protein, and fecal calprotectin were assessed in the overall population and for patients in the biologic-naïve or prior biologic failure subgroups. A significantly greater percentage of patients in the 130-mg ustekinumab (20.0%; P= .015) or approximately 6-mg/kg ustekinumab (20.2%; P= .012) groups achieved symptomatic remission at week 2 vs placebo (12.9%). Mean [SD] changes from baseline in daily stool number on day 7 were greater in the ustekinumab groups (-1.1 [2.6] in 130 mg [P= .065] and -1.2 [2.5] in ∼6 mg/kg [P= .017]) vs placebo (-0.7 [2.7]). The percentage of patients with Mayo stool frequency subscore of 1 or less and rectal bleeding subscore of 0 increased from baseline through week 16 for both ustekinumab groups. Significant improvements in partial Mayo scores were observed by week 2 in both ustekinumab groups vs placebo (P ≤ .001). Significantly more patients in the ustekinumab groups had normalized C-reactive protein levels from week 2 to week 8 vs placebo (P ≤ .05). Similar results were observed with normalized fecal calprotectin levels between week 2 and week 4 (P ≤ .05). Ustekinumab improved symptoms in patients with UC compared with placebo in as early as 7 days, indicating rapid onset of effect after induction. ClinicalTrials.gov: NCT02407236.

DOP38 Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1

Abstract Background Upadacitinib (UPA), an oral, reversible JAK inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, or tyrosine kinase 2 (TYK2), demonstrated significantly greater efficacy compared with placebo (PBO) for induction of remission in patients with moderately to severely active ulcerative colitis (UC) in two phase 3 trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026). This analysis evaluated the efficacy of UPA on early symptomatic improvement for the first 14 days, using pooled data from U-ACHIEVE Induction and U-ACCOMPLISH. Methods U-ACHIEVE and U-ACCOMPLISH were multicentre, double-blind, PBO-controlled trials that enrolled patients who have had moderately to severely UC with an Adapted Mayo Score of 5 to 9 points and centrally reviewed endoscopy subscore of 2 to 3. A total of 998 patients were randomized to receive UPA 45mg once daily (QD) (n=658) or PBO (n=328) for 8 weeks (wks) in a 2:1 ratio. First dose of study drug was administered on Day 0. Improvement in symptoms including stool frequency subscore (SFS), rectal bleeding subscore (RBS), abdominal pain, and bowel urgency were analysed from daily symptom diary data. Multivariate regression analysis was used to determine if early changes in UC symptoms could be used to evaluate a potential correlation with patients’ likelihood of achieving clinical response or clinical remission per Adapted Mayo score at the end of induction. Results Baseline characteristics were similar between both treatment groups. Patients treated with UPA 45 mg QD experienced significant improvement in daily symptoms, with significantly more subjects achieving SFS≤1 (p&amp;lt;0.001), RBS of 0 (p&amp;lt;0.05), and SFS of 0 (p&amp;lt;0.05) as early as day 1 and maintained through day 14 (Figure 1). A significantly higher percentage of patients who received UPA 45 mg QD compared to PBO, achieved abdominal pain=0 and the absence of bowel urgency within 3 days of beginning treatment through day 14 (p&amp;lt;0.05). Multivariate analysis revealed that patients who achieved day 7 SFS≤1 (OR 2.42, 95% CI, 1.53–3.82) were more likely to attain clinical response (Table). Patients who attained day 7 SFS≤1 (OR 2.53, 95% CI 1.59–4.00) or day 7 bowel urgency absent (OR 2.40, 95% CI 1.52–3.79) were more likely to achieve clinical remission at week 8. Conclusion UPA 45 mg QD significantly improved UC symptoms as early as day 1, providing patients with rapid symptom relief. Patients who achieved early symptom improvement were more likely to attain clinical remission or clinical response at week 8. [Clinicaltrials.gov, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026)]

S773 Rapidity of Symptom Control with Upadacitinib Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From Two Randomized Phase 3 Studies

Introduction: Upadacitinib (UPA) is an oral, selective JAK inhibitor investigated for treatment of several immune-mediated inflammatory diseases, including ulcerative colitis (UC). Safety and efficacy of UPA in patients (pts) with moderately to severely active UC were studied in the phase 3 induction trials, U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026). We assessed early (week 2) symptomatic improvement and decrease in biomarkers of inflammation during induction therapy with UPA 45 mg once daily (QC) compared with placebo (PBO). Methods: In the multicentre, double-blind, PBO-controlled U-ACHIEVE and U-ACCOMPLISH trials, pts with moderately to severely active UC were randomized 2:1 to UPA 45 mg QD or PBO for 8 weeks. This analysis evaluated the proportions of pts with clinical remission (per partial Mayo score), clinical response (per partial Mayo score), stool frequency subscore (SFS) ≤1, and rectal bleeding subscore (RBS) of 0, as well as change from baseline in fecal calprotectin and high-sensitivity C-reactive protein (hsCRP) at week 2 with UPA vs PBO. Statistical comparison between the two groups was performed according to the Cochran-Mantel-Haenszel test adjusted for baseline corticosteroid use (yes or no), baseline Adapted Mayo score (≤7 or >7), according to prior biologic response (bio-IR, biologic inadequate response/bio failure; non-bio-IR, nonbiologic inadequate response/non-bio-failure). Results: As early as week 2, a significantly higher proportion of pts who received UPA achieved clinical remission per partial Mayo score (23%) compared with PBO (5%; treatment difference, [95% CI]: 17.4 [11.8, 23.1]; P < 0.001) in U-ACHIEVE. Results were similar in U-ACCOMPLISH at week 2: UPA (31%) versus PBO (3%); treatment difference (95% CI): 26.5 (20.9, 32.1; P < 0.001). Similarly, higher proportions of pts receiving UPA 45 mg QD achieved other efficacy endpoints, including clinical response, SFS ≤1 and RBS = 0, at week 2 vs PBO (Table 1). Significant decreases from baseline in markers of inflammation (fecal calprotectin and hsCRP levels) were also observed with UPA vs PBO in both trials (Table 1). Safety was comparable with the known safety profile of UPA, and no new safety signals were identified. Conclusion: UPA 45 mg QD achieved rapid improvement in both symptomatic and objective biomarker measures as early as week 2 compared with PBO in pts with moderately to severely active UC. The results demonstrate rapid onset of treatment effect with UPA.Table 1.: Baseline Clinical Characteristics of Patients with Perianal Crohn's Disease

Early symptomatic benefit indicates long-term prognosis after transcatheter mitral valve edge-to-edge repair in functional and degenerative etiology

BackgroundMitral regurgitation (MR) is common in patients with heart failure and constitutes an independent risk factor for adverse prognosis besides NYHA-class. The predictive value of dyspnea reduction after transcatheter mitral valve repair (TMVr) on outcome has not been investigated up to now. Methods and resultsWe enrolled 627 consecutive patients (47.0% female, 57.4% functional MR; median follow-up 486 days[IQR 157/961]; survival status available in 96.8%; symptoms assessed in n = 556 at baseline / n = 406 at 1 month) treated with isolated percutaneous mitral valve edge-to-edge repair in our center from 06/2010–03/2018 (exclusion of combined forms of TMVr) in a monocentric retrospective analysis. Survival was 97.6% at discharge, 73.9% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7-years. Before TMVr, NYHA-classes III/IV were found in 89.0%. Of these, 74.7% reported symptomatic relief (reduction in NYHA-class) one month after procedure (NYHA class recorded in 406 patients at 30 days). NYHA-classes III/IV were documented in 37.2% (p < 0.001) at 30 days and in 36.6% (p < 0.001) at 1 year without significant changes between the follow-ups. Dyspnea reduction was accompanied by significantly improved long-term survival (1 year, 89.1 vs 71.2%, p = 0.001, 2 years: 75.5 vs 58.7%, p = 0.039) and was identified as an independent predictor for lower mortality (1-year HR for increased mortality by missing symptomatic improvement 2.94 [95%CI 1.53–5.65], p = 0.001; long-term HR 1.95 [95%CI 1.29–2.94], p = 0.001) independently in both etiologies of MR. ConclusionTMVr by edge-to-edge therapy enables early and sustainable symptomatic improvement in nearly 75% of the symptomatic patients. The simple assessment of postinterventional changes in NYHA-class might serve as an independent predictor for mid- and long-term prognosis in both FMR and DMR.

Early Improvement of Psychiatric Symptoms with Long-Acting Injectable Antipsychotic Predicts Subsequent Social Functional Remission in Patients with Schizophrenia.

PurposeThe aim of this study was to clarify whether early symptomatic improvement in response to a long-acting injectable antipsychotic (LAI) contributes to subsequent social functional remission in patients with schizophrenia using the previous clinical trial data (EudraCT registration number: 2011-004889-15). Associations between other factors and social functional remission were also explored.Patients and MethodsWe analyzed 428 patients with schizophrenia in which the personal and social performance scale (PSP) and the involvement evaluation questionnaire (IEQ) at the time of the base line were recorded. Social functional remission was defined as participants who scored PSP >70 at the end of 65 weeks. Logistic regression analyses were done to examine associations between social functional remission and clinical and demographic characteristics including early symptomatic response evaluated by Positive and Negative Syndrome Scale (PANSS) at week one.ResultsOne hundred out of 428 patients showed social functional remission at the end of the observation period. Shorter duration of illness, higher baseline score of supervision evaluated by IEQ and higher baseline PSP were significantly associated with the social functional remission. Improvement of positive subscale of PANSS at one week was significantly associated with later social functional remission when baseline PSP scores were excluded from predictive variables.ConclusionShorter duration of illness, residual type of schizophrenia, higher baseline score of supervision and higher baseline social functioning were predictors of subsequent social functional remission. Although its effect seems to be limited, early symptomatic improvement could be also was a predictor of social functional remission.

Week 2 Symptomatic Response with Vedolizumab as a Predictive Factor in Japanese Anti-TNFα-Naive Patients with Ulcerative Colitis: A post hoc Analysis of a Randomized, Placebo-Controlled Phase 3 Trial

Background and Aim: To evaluate the onset of symptomatic response with vedolizumab in patients with moderate-to-severe ulcerative colitis in Japan. Methods: Patients were randomized to receive vedolizumab 300 mg or placebo at Weeks 0, 2, and 6. Mayo subscores were analyzed in patients with baseline stool frequency (SF) ≥1 and rectal bleeding (RB) ≥1. In patients with baseline SF ≥2 and RB ≥1, the proportion who achieved SF ≤1 and RB = 0 was determined. Results: Patients were randomized to vedolizumab (n = 164) or placebo (n = 82). Decrease from baseline in mean SF subscore was greater with vedolizumab versus placebo from Week 2 (−6.6%; 95% confidence interval [CI], −16.2, 3.0), with a greater difference in anti-tumor necrosis factor (TNF)α-naive patients (vedolizumab vs. placebo, −13.2%; 95% CI, −29.7, 3.3). Mean percentage decrease from baseline RB subscore was numerically greater with vedolizumab versus placebo from Week 6 in anti-TNFα-naive patients (−10.7%; 95% CI, −33.0, 11.5). More patients in the anti-TNFα-naive subgroup achieved SF ≤1 and RB = 0 with vedolizumab versus placebo at Week 2 (14.8%; 95% CI, 2.5, 27.0) and Week 6 (20.3%; 95% CI, 4.4, 36.2). Patients with SF ≤1 and RB = 0 at Week 2 had higher clinical response, clinical remission, and mucosal healing rates at Week 10 than those without. Conclusions: Our results indicate that vedolizumab induces a rapid symptomatic response, particularly in anti-TNFα-naive patients, and suggest that early symptomatic improvement predicts treatment response at Week 10 (NCT02039505).

Rib-sparing scalenectomy for neurogenic thoracic outlet syndrome: Early results

ObjectiveNeurogenic thoracic outlet syndrome (NTOS) is no longer either “controversial” or “disputed”; however, its optimal surgical management remains unclear. Many thoracic outlet decompression procedures are performed by first rib resection, usually via a transaxillary route. MethodsA retrospective review of a prospectively maintained NTOS database was performed. Patients with NTOS associated with a cervical rib and those with recurrent NTOS were excluded from the present analysis. All study patients had satisfied a 5-point clinical diagnostic protocol and had experienced a positive response to a local anesthetic scalene block. Surgical decompression included anterior, minimus, and middle scalenectomy and brachial plexus neurolysis via a supraclavicular incision and pectoralis minor tenotomy through a small vertical infraclavicular incision. No first ribs were excised. All the patients had completed QuickDASH (11-item version of the Disability of the Arm, Shoulder, and Hand questionnaire) preoperatively and at 3 or 6 months postoperatively. ResultsFrom 2011 to 2019, 504 thoracic outlet decompression procedures had been performed in 442 patients. The average operative time was 1.15 hours, and the average hospital length of stay was 1.05 days. Major complications, including intraoperative arterial injury, postoperative wound hematoma requiring reoperation, and chylothorax, occurred in 7 patients (1.4%). All but 2 patients (99.6%) had symptomatic improvement. Using a more rigorous definition of operative success of ≥50% improvement in the 3- or 6-month QuickDASH score, 458 rib-sparing NTOS operations (90.9%) were successful. In contrast to the mean preoperative QuickDASH score of 62.6, the average postoperative QuickDASH score was 25.2 (P = .001). ConclusionsThese results suggest that (1) adherence to a rigorous preoperative diagnostic regimen, including performance of a scalene block, ensures, at the least, that surgery for NTOS can be successfully restricted to patients actually with the condition; (2) fibrotic, contracted scalene muscles are the cause of NTOS; (3) the first rib does not require removal for successful surgical treatment of NTOS; and (4) 90% of the patients so treated can expect significant early symptomatic and functional improvement.

Adjunctive techniques to minimize thrombotic complications following microfoam sclerotherapy of saphenous trunks and tributaries

ObjectiveThrombus extension into the deep venous system following superficial vein chemical ablation with Varithena polidocanol microfoam has been reported. The objective of this study was to assess the effect of intraoperative improved techniques during treatment for patients with symptomatic varicose veins and their impact on extension of thrombus into deep veins. MethodsA retrospective review of a prospectively maintained database was performed. All patients who underwent endovenous chemical ablation with polidocanol microfoam (Varithena, Boston Scientific, Marlborough, Mass) for symptomatic superficial axial and tributary vein reflux were identified. Patients had postoperative duplex (48-72 hours) scanning after the procedure; those who did not adhere to the recommended follow-up were excluded. Demographic data, CEAP Classification, Venous Clinical Severity Score, procedure details, and follow-up data were abstracted. ResultsBetween April 2018 and August 2020, 157 limbs in 122 patients were treated with Varithena microfoam; 129 limbs in 99 patients met our inclusion criteria. Veins treated included the great saphenous vein (n = 89), anterior accessory saphenous vein (n = 15), small saphenous vein (n = 14), and tributary veins (n = 56). Adjunctive techniques during treatment included intraoperative elevation of the limb to greater than 45°, ultrasound mapping and digital occlusion of large perforator veins, limitation of foam volume per session, injection of sterile saline before treatment, and compression of the limb in the elevated position. The preoperative Venous Clinical Severity Score was 11.4 and decreased after treatment to 9.7. The immediate closure rate was 95% with 81% overall symptomatic relief at last follow-up. The mean follow-up was 113.5 days for the entire cohort; two limbs (1.5%) required postoperative anticoagulation for thrombus extension into the deep venous system (common femoral vein n = 1; popliteal vein n = 1) postoperatively for a mean of 22 days. Both resolved with anticoagulation. One asymptomatic limb developed a femoral vein deep venous thrombosis and one symptomatic late deep venous thrombosis was noted 4 months after the procedure. Postoperative pain and phlebitis were reported in 15.6% and 14.8% of patients, respectively, and all had resolved at last follow-up. No pulmonary emboli were noted and no neurologic or visual adverse events were recorded. ConclusionsAdjunctive techniques during microfoam ablation decreased thrombotic complications in our series compared with those reported in earlier phase III clinical trials. Excellent early closure and symptomatic improvement were also noted. Endovenous microfoam ablation with Varithena is a safe and effective nontumescent, nonthermal alternative to laser and radiofrequency ablation.

Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study.

AimSacubitril/valsartan is a first‐in‐class angiotensin receptor‐neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many peptides metabolized by NEP suggest multifaceted potential consequences of its inhibition. We sought to evaluate the short‐term changes in serum endorphin (EP) values and their relation with patients' physical functioning after initiation of sacubitril/valsartan treatment.Methods and resultsA total of 105 patients with heart failure with reduced ejection fraction, who were candidates for sacubitril/valsartan treatment, were included in this prospective, observational, multicentre, and international study. In a first visit, and in agreement with current guidelines, treatment with angiotensin‐converting enzyme inhibitors or angiotensin receptor blocker was replaced by sacubitril/valsartan because of clinical indication by the responsible physician. By protocol, patients were reevaluated at 30 days after the start of sacubitril/valsartan. Serum levels of α‐ (α‐EP), γ‐Endorphin (γ‐EP), and soluble NEP (sNEP) were measured using enzyme‐linked immunoassays. New York Heart Association (NYHA) functional class was used as an indicator of patient's functional status. Baseline median levels of circulating α‐EP, γ‐EP, and sNEP were 582 (160–772), 101 (37–287), and 222 pg/mL (124–820), respectively. There was not a significant increase in α‐EP nor γ‐EP serum values after sacubitril/valsartan treatment (P value = 0.194 and 0.102, respectively). There were no significant differences in sNEP values between 30 days and baseline (P value = 0.103). Medians (IQR) of Δα‐EP, Δγ‐EP, and ΔsNEP between 30 days and baseline were 9.3 (−34 − 44), −3.0 (−46.0 − 18.9), and 0 units (−16.4 − 157.0), respectively. In a pre–post sacubitril/valsartan treatment comparison, there was a significant improvement in NYHA class, with 36 (34.3%) patients experiencing improvement by at least one NYHA class category. Δα‐EP and ΔsNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Δα‐EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment.ConclusionsThese preliminary data suggest that beyond the haemodynamic benefits achieved with sacubitril/valsartan, the altered cleavage of endorphin peptides by NEP inhibition may participate in patients' symptoms improvement.

Early response to psychological therapy as a predictor of depression and anxiety treatment outcomes: A systematic review and meta-analysis.

Previous studies indicate that early symptomatic improvement, typically observed during the first 4 weeks of psychological therapy, is associated with positive treatment outcomes for a range of mental health problems. However, the replicability, statistical significance, and magnitude of this association remain unclear. The current study reviewed the literature on early response to psychological interventions for adults with depression and anxiety symptoms. A systematic review and random effects meta-analysis were conducted, including studies found in Medline, PsychINFO, SCOPUS, Web of Science, and through reference lists and reverse citations. Twenty-five eligible studies including 11,091 patients measured early response and examined associations with posttreatment outcomes. It was possible to extract and/or calculate effect size data from 15 studies to conduct a meta-analysis. A large pooled effect size (g = 0.87 [95% confidence interval: 0.63-1.10], p < .0001) indicated that early responders had significantly better posttreatment outcomes compared to cases without early response, and this effect was larger in anxiety (g = 1.37) compared to depression (g = 0.76) measures. Most studies were of good quality and there was no evidence of publication bias. The main limitations concerned insufficient statistical reporting in some studies, which precluded their inclusion in meta-analysis, and it was not possible to examine effect sizes according to different outcome questionnaires. There is robust and replicated evidence that early response to therapy is a reliable prognostic indicator for depression and anxiety treatment outcomes.

Vedolizumab Demonstrates Early Symptomatic Improvement in Ulcerative Colitis: A GEMINI 1 Post Hoc Analysis

BACKGROUND: Vedolizumab (VDZ) achieves long term clinical remission and mucosal healing in patients (pts) with moderately-to-severely active ulcerative colitis (UC). Relief of rectal bleeding (RB) and stool frequency (SF) remain important treatment goals for pts and key indicators of remission for physicians. We aimed to characterize early symptomatic response with VDZ, specifically evaluating the timing of RB and SF improvement. METHODS: We assessed symptomatic improvement with VDZ through post-hoc analysis of GEMINI 1 data. Pts with active, moderate-to-severe UC were randomized to receive double-blind placebo (PBO) or VDZ at weeks (wks) 0 and 2 during the 6-wk induction phase. Mayo clinic SF subscores (SFS) and RB subscore (RBS) were evaluated at 0, 2, 4, and 6 wks. Mean subscores and mean percent change from baseline (BL) were reported for the overall population and in those who were tumor necrosis factor antagonist (anti-TNF) naïve. The percentages of pts who reached SFS≤1 and/or RBS=0 were also determined. RESULTS: In anti-TNF-naïve pts, greater percentage decreases in mean SFS from BL were observed with VDZ vs PBO, reaching statistical significance at wks 4 and 6 as suggested by the non-overlapping 95% confidence intervals. Percent change from baseline (95%CI) at wks 2, 4, and 6 were -19.9(-28.0, -11.8), -35.7(-45.2, -26.2) and -36.5(-45.0, -28.0) respectively for VDZ and -5.0(-15.7, 5.7), -0.4(-12.8, 11.9) and -12(-23.4, -0.6) respectively for PBO. The same trends were observed in the overall population without reaching statistical significance. Percent change from baseline (95%CI) at wks 2, 4, and 6 were -12.3(-18.6, -6.0), -23.5(-31.2, -15.7) and -25.0(-31.6, -18.3) respectively for VDZ and -6.4(-14.2, 1.5), -9.9(-19.5, -0.3), and -12.4(-20.8, -4.0) respectively for PBO. Similarly, a numerically greater percentage decrease from BL in RBS was observed with VDZ vs PBO, reaching statistical significance at wk 6 in both anti-TNF-naïve and overall populations. Percent change from baseline (95%CI) at wks 2, 4, and 6 for anti-TNF-naïve pts were -29.8(-39.2, -20.4), -45.6(-55.4, -35.9) and -59.0(-67.6, -50.3) respectively for VDZ, and -19.8 (-32.3, -7.3), -28.0(-40.8, -15.3) and -27.1(-38.7, -15.4) respectively for PBO. Percent change from baseline (95%CI) at wks 2, 4, and 6 for overall pts were -28.6 (-35.5, -21.6), -42.3(-49.5, -35.1) and -49.5 (-57.0, -41.9) respectively for VDZ and -20.7 (-29.4, -12.1), -29.6(-38.4, -20.7) and -26.8 (-36.3, -17.3) respectively for PBO. Significantly higher percentages of pts achieved SFS≤1 or RBS=0 with VDZ vs PBO at wk 6 (32% higher with 95%CI:19.5-44.6 and 22.9% higher with 95%CI:9.8-36.0, respectively) and as early as wk 2 (22.2% higher with 95%CI of 9.6-34.9 and 12.3% higher with 95%CI:0.6-24.1, respectively) among the anti-TNF-naïve population. A composite of SFS≤1 and RBS=0 was achieved in a significantly greater percentage of pts with VDZ than PBO at all time points for both anti-TNF naïve and overall populations with treatment differences of 15.7% and 9.0% at Week 2. CONCLUSION(S): Symptomatic improvements were achieved with VDZ as early as wk 2, with greater differences from PBO observed in anti-TNF-naïve pts. These results highlight the rapid onset of VDZ in UC; however, assessing efficacy at wk 14 and beyond for those who exhibit a more gradual response should be used to inform clinical practice.

Knee Arthrodesis in a Patient with Charcot Neuroarthropathy Secondary to Familial Amyloid Polyneuropathy: A Case Report.

We report a rare case of severe Charcot neuroarthropathy of the knee secondary to familial amyloid polyneuropathy, which was treated surgically with a knee arthrodesis. This treatment allowed an early symptomatic and functional improvement and a short consolidation time without any major complications. Neuropathy is the earliest and most major burden in patients with familial amyloid polyneuropathy; it requires careful evaluation and adequate treatment aimed at preventing or slowing the progression of secondary damage, involving Charcot neuroarthropathy, that may occur. Surgical arthrodesis with antegrade intramedullary nailing may be appropriate in a patient with severe Charcot neuroarthropathy of the knee.

Vedolizumab Demonstrates Early Symptomatic Improvement in Ulcerative Colitis: A GEMINI 1 Post hoc Analysis

Vedolizumab Demonstrates Early Symptomatic Improvement in Ulcerative Colitis: A GEMINI 1 Post hoc Analysis