Search

As an international network of historians and social scientists who study approaches to the management of drugs across time and place, we have noticed the effort to redefine addiction as a chronic, relapsing brain disease (CRBD). The CRBD model is promoted as a route to destigmatize addiction and to empower individuals to access treatment that works within that model’s terms.1 CRBD usefully recognizes that brain-based neural adaptations place individual brains in chronic states of readiness to relapse. But brains are housed inside of people. Substance use is biological, social, and political; our concepts and approaches to complex questions surrounding substance use must be, too.2,3 By overlooking the sociopolitical dynamics and inequalities bound up with substance use, the CRBD model can paradoxically further marginalize people who use drugs by positing them as neurobiologically incapable of agency or choice. We are concerned that the CRBD model paints drug users as individuals whose exclusion from social, economic, and political participation is justified by their biological flaws and damaged brains.

Aims There is considerable controversy regarding optimal management of patients with paraesophageal hiatus hernia (pHH). This survey aims at identifying recommended strategies for work-up, surgical therapy, and postoperative follow-up using Delphi methodology. Methods We conducted a 2-round, 33-question, web-based Delphi survey on perioperative management (preoperative work-up, surgical procedure and follow-up) of non-revisional, elective pHH among European surgeons with expertise in upper-GI. Responses were graded on a 5-point Likert scale and analyzed using descriptive statistics. Items from the questionnaire were defined as “recommended” or “discouraged” if positive or negative concordance among participants was > 75%. Items with lower concordance levels were labelled “acceptable” (neither recommended nor discouraged). Results Seventy-two surgeons with a median (IQR) experience of 23 (14–30) years from 17 European countries participated (response rate 60%). The annual median (IQR) individual and institutional caseload was 25 (15–36) and 40 (28–60) pHH-surgeries, respectively. After Delphi round 2, “recommended” strategies were defined for preoperative work-up (endoscopy), indication for surgery (typical symptoms and/or chronic anemia), surgical dissection (hernia sac dissection and resection, preservation of the vagal nerves, crural fascia and pleura, resection of retrocardial lipoma) and reconstruction (posterior crurorrhaphy with single stitches, lower esophageal sphincter augmentation (Nissen or Toupet), and postoperative follow-up (contrast radiography). In addition, we identified “discouraged” strategies for preoperative work-up (endosonography), and surgical reconstruction (crurorrhaphy with running sutures, tension-free hiatus repair with mesh only). In contrast, many items from the questionnaire including most details of mesh augmentation (indication, material, shape, placement, and fixation technique) were “acceptable”. Conclusions This multinational European Delphi survey represents the first expert-led process to identify recommended strategies for the management of pHH. Our work may be useful in clinical practice to guide the diagnostic process, increase procedural consistency and standardization, and to foster collaborative research.

Polyarteritis nodosa (PAN) is a medium vessel vasculitis with necrotising vascular changes along with multisystemic involvement. Due to variable initial presentations, diagnosis of systemic PAN in children requires a comprehensive work up. In addition, systemic PAN needs an aggressive therapy. Mycophenolate mofetil is an emerging newer alternative for the treatment of PAN. We report a case of childhood systemic PAN who initially presented with subtle signs like reduced sensation over lateral foot, non-deforming arthritis and multiform rashes. After comprehensive aetiological work up, nerve biopsy and supporting evidence clinched the diagnosis. Vasculitis in children presenting with benign subtle signs is sometimes a diagnostic challenge to clinicians. Our case highlights the importance of lateral thinking while dealing with non-specific multisystemic signs. Evidence of successful treatment of PAN with mycophenolate mofetil is gradually being built up. It is also described to result lower relapse and increased treatment free survival rate.

Purpose: To evaluate recurrence rates and risk factors among women with stage IA1 cervical cancer without lymph vascular space invasion managed conservatively. Methods: retrospective review of women with stage IA1 squamous cervical cancer who underwent cold knife cone or loop electrosurgical excision procedure, between 1994 and 2015, at a gynecologic oncology center in Southern Brazil. Age at diagnosis, pre-conization findings, conization method, margin status, residual disease, recurrence and survival rates were collected and analyzed. Results: 26 women diagnosed with stage IA1 squamous cervical cancer without lymphovascular space invasion underwent conservative management and had at least 12 months follow-up. The mean follow-up was 44.6 months. The mean age at diagnosis was 40.9 years. Median first intercourse occurred at age 16 years, 11.5% were nulliparous and 30.8% were current or past tobacco smokers. There was one Human immunodeficiency virus positive patient diagnosed with cervical intraepithelial neoplasia grade 2 at 30 months after surgery. However, there were no patients diagnosed with recurrent invasive cervical cancer and there were no deaths due to cervical cancer or other causes in the cohort. Conclusion: Excellent outcomes were noted in women with stage IA1 cervical cancer without lymphovascular space invasion and with negative margins who were managed conservatively, even in a developing country. Resumo Objetivo: Avaliar recidiva e seus fatores de risco em mulheres com câncer do colo do útero estádio IA1 sem invasão do espaço linfovascular tratadas conservadoramente. Métodos: Estudo de coorte retrospectivo de pacientes com câncer do colo do útero IA1 escamoso submetidas a cone do colo do útero, entre 1994 e 2015, em um centro de ginecologia oncológica do sul do Brasil. Foram revisados e analisados idade no diagnóstico, achados pré-conização, método de conização, margens, doença residual, recorrência e sobrevida. Resultados: 26 mulheres diagnosticadas com câncer do colo do útero estádio escamoso sem invasão do espaço linfovascular foram submetidas a tratamento conservador, com seguimento mínimo de 12 meses. O tempo médio de seguimento foi 44,6 meses. A média de idade no diagnóstico foi 40,9 anos. A primeira relação sexual ocorreu aos 16 anos (mediana), 11,5% eram nulíparas e 30,8% eram tabagistas atuais ou passadas. Houve um caso de recidiva de neoplasia intraepitelial cervical grau 2 aos 30 meses em uma paciente com vírus da imunodeficiência humana. Não houve pacientes diagnosticados com câncer de colo do útero invasor recorrente, e não houve mortes por câncer do colo do útero ou outras causas. Conclusão: Os resultados observados após tratamento conservador em mulheres com câncer cervical escamoso IA1 sem invasão do espaço linfovascular com margens negativas foram excelentes, mesmo em um país em desenvolvimento.

Current literature suggests an increased risk of venous thromboembolism (VTE) in people living with HIV (PLWH) with poorly controlled viraemia and immunodeficiency. VTE treatment guidelines do not specifically address anticoagulation management in PLWH. We report a case of a 33-year-old woman diagnosed with an unprovoked pulmonary embolism (PE) and deemed protein S deficient. Three years later, she was diagnosed with AIDS. Antiretroviral therapy (ART) was promptly initiated with viral suppression and immune reconstitution within 12 months. Eight years after her initial PE, the patient self-discontinued warfarin. Multiple repeat protein S values were normal. ART without anticoagulation has continued for 3 years with no thrombotic events. This case describes a patient with VTE presumably secondary to undiagnosed HIV with possible consequent acquired protein S deficiency. Additional research is needed to understand the characteristics of PLWH with VTE who may warrant long-term anticoagulation as opposed to shorter courses.

Actinomycosis is a rare invasive bacterial disease that is characterised by granulomatous inflammation often mistaken as malignancy. Traditionally, this has been managed with prolonged courses of antibiotics with durations up to 6–12 months. Surgical intervention as an adjuvant treatment has been shown to reduce the length of antibiotic treatment significantly to 4 weeks. We report a case of cervicofacial actinomycosis in a 12-year-old girl who was adequately treated with an 11-day course of antibiotics without surgical intervention and shows no signs of recurrence at 6 months post-treatment.

The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP).Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP.Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP.Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.

Major depressive disorder (MDD) which comes to transcranial magnetic stimulation (TMS) is prone to relapse. Cluster maintenance (CM) TMS is courses of 5 treatments delivered over 2.5-5 days, separated by monthly or greater non-treatment periods. Our aim was to characterize the outcomes of 100 courses of CM TMS.This was a Quality Assurance/Clinical Audit study. We studied consecutive CM TMS courses provided to private hospital inpatients. Mood was rated (on admission and discharge) using the six-item Hamilton depression rating (HAMD6) and the Clinical Global Impression - Severity (CGI-S) scales. We also applied recent STAR*D criteria which are designed to measure the 'clinical change' expected to impact patient function [16].For the total sample, using the HAMD6, 83% of courses featured relapse or partial relapse on admission, and 81% featured remission on discharge. Of 46 courses featuring HAMD6 relapse on admission, 74% featured remission on discharge. For the 100 courses the HAMD6 discharge scores were significantly lower than the admission scores (p = 2.0 × 10For courses featuring relapse or partial relapse on admission, CM TMS converted greater than 70% to remission at discharge. It produced statistically significant reductions in HAMD6 and CGI-S scores, and using STAR*D criteria, at least 'clinically meaningful' change was extensively demonstrated. This evidence indicates CM TMS should be readily available to people living with relapsing MDD.

Background and objective To determine the risk factors for recurrence after endovascular embolization of posterior communicating artery aneurysms (PcomA). Methods We retrospectively analyzed a cohort of 163 patients harboring 172 PocmAs who were treated with endovascular embolization from January 2019 to December 2020. The patients were divided into recurrence and stable groups depending on outcome. Univariate and logistic regression analyses were performed to determine the potential risk factors of recurrence during follow-up. Results Of the total 163 patients harboring 172 aneurysms, 107 were treated with simple coil occlusion and 65 were treated with stent-assisted coil embolization. There were significant differences in aneurysm sizes and use of non-stent-assisted coil embolizations between the groups (P Conclusion Non-stent-assisted coil embolization, as well as packing density and Raymond grades II grade III are associated with recurrence after endovascular treatment of PcomA.

Background: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models. Objective: To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models. Methods: Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement. Results: 4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 [95% CI 0.62-0.80]; marginal structural model: 0.71 [0.62-0.80]), and higher probability of disability improvement (PS matching: 1.21 [1.02 -1.43]; marginal structural model 1.43 1.19 -1.72]). There was no evidence of a difference in the magnitude of effect between the two methods. Conclusions: The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts.

To compare return to sports, functional outcomes, and recurrences rates between female and male athletes following arthroscopic Bankart repair (ABR).A retrospective comparative study was performed between male and female athletes who underwent an ABR between January 2008 and December 2019. Sports practiced primarily by men in our practice (including rugby, soccer, boxing, and martial arts) were excluded. Functional outcomes included the Rowe score, visual analog scale (VAS) for pain, and shoulder-dependent sports ability measured with the Athletic Shoulder Outcome Scoring System (ASOSS). Return to sport, recurrence, and revisions were evaluated. Additionally, we assessed the period (months) between surgery and recurrence events.A total of 58 female and 106 male patients were available for analysis at a median follow-up of 60 (interquartile range [IQR], 36-84) months. Ninety-one percent of the patients (n = 150) returned to sports and 84% (n = 126) returned to their preinjury level at a median of 6 months (IQR, 5-8) postoperatively. There were no differences in the rate of return to sports between females and males (91 vs 92% respectively, P = .997). There were no differences between the groups regarding postoperative functional outcomes, with most patients achieving the minimal clinically significant difference (Rowe: 98% female and 99% male, P = .584; ASOSS: 100% female and 99% male, P = .646). The overall recurrence rate was 9.7% (n = 16), with a rate of 10.3% (n = 6) in female and 9.4% (n = 10) in male athletes (P = .851). Time to event analysis showed that the median time to recurrence was 48 months in both groups (P = .848). The overall revision rate was 3% (n = 4), without significant differences between groups (P = .556).When compared within similar sports, there does not appear to be sex-related differences in functional outcomes, recurrence, or return to play following ABR.III, retrospective comparative study.

Background: The high recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy usually results in poor prognosis. To the best of our knowledge, no study has reported the efficacy of immune checkpoint inhibitors (ICIs) plus targeted therapies on preventing HCC recurrence after hepatectomy. Thus, the aim of this study was to investigate the benefits and safety of applying adjuvant ICIs plus targeted therapies after hepatectomy for patients at high risk of HCC recurrence. Methods: A total of 196 patients with any risk factors for recurrence who underwent hepatectomy for HCC were reviewed in this retrospective study. Results: Compared with the control group (n = 158), ICIs plus targeted therapies (n = 38) had a significantly higher recurrence-free survival (RFS) rate in univariate analysis (HR, 0.46; 95% confidence interval [CI], 0.24–0.90; p = 0.020), multivariate analysis (adjusted HR, 0.62; 95%CI, 0.49–0.79; p < 0.001) and propensity score-matched analysis (HR, 0.35; 95%CI, 0.16–0.75; p = 0.005). Subgroup analyses also showed that postoperative adjuvant ICIs plus targeted therapies might reduce HCC recurrence in patients with the most of risk factors. Conclusion: Postoperative adjuvant ICI plus targeted therapies may reduces early HCC recurrence in patients with a high risk of recurrence, and the treatments are well tolerated.

PURPOSE Nonresponse and relapse after CD19-chimeric antigen receptor (CAR) T-cell therapy continue to challenge survival outcomes. Phase II landmark data from the ELIANA trial demonstrated nonresponse and relapse rates of 14.5% and 28%, respectively, whereas use in the real-world setting showed nonresponse and relapse rates of 15% and 37%. Outcome analyses describing fate after post-CAR nonresponse and relapse remain limited. Here, we aim to establish survival outcomes after nonresponse and both CD19+ and CD19– relapses and explore treatment variables associated with inferior survival. METHODS We conducted a retrospective multi-institutional study of 80 children and young adults with B-cell acute lymphoblastic leukemia experiencing nonresponse (n = 23) or relapse (n = 57) after tisagenlecleucel. We analyze associations between baseline characteristics and these outcomes and establish survival rates and salvage approaches. RESULTS The overall survival (OS) at 12 months was 19% across nonresponders (n = 23; 95% CI, 7 to 50). Ninety-five percent of patients with nonresponse had high preinfusion disease burden. Among 156 morphologic responders, the cumulative incidence of relapse was 37% (95% CI, 30 to 47) at 12 months (CD19+; 21% [15 to 29], CD19–; 16% [11 to 24], median follow-up; 380 days). Across 57 patients experiencing relapse, the OS was 52% (95% CI, 38 to 71) at 12 months after time of relapse. Notably, CD19– relapse was associated with significantly decreased OS as compared with patients who relapsed with conserved CD19 expression (CD19– 12-month OS; 30% [14 to 66], CD19+ 12-month OS; 68% [49 to 92], P = .0068). Inotuzumab, CAR reinfusion, and chemotherapy were used as postrelapse salvage therapy with greatest frequency, yet high variability in treatment sequencing and responses limits efficacy analysis across salvage approaches. CONCLUSION We describe poor survival across patients experiencing nonresponse to tisagenlecleucel. In the post-tisagenlecleucel relapse setting, patients can be salvaged; however, CD19– relapse is distinctly associated with decreased survival outcomes.

BACKGROUND: The inflammatory potential of the diet has been associated with colorectal cancer (CRC) risk, but its association with CRC prognosis is unclear. OBJECTIVE: To investigate the inflammatory potential of the diet in relation to recurrence and all-cause mortality among persons diagnosed with stage I to III CRC. METHODS: Data of the COLON study, a prospective cohort among CRC survivors were used. Dietary intake, 6 mo after diagnosis, was assessed by using a food frequency questionnaire and was available for 1631 individuals. The empirical dietary inflammatory pattern (EDIP) score was used as a proxy for the inflammatory potential of the diet. The EDIP score was created by using reduced rank regression and stepwise linear regression to identify food groups that explained most of the variations in plasma inflammatory markers (IL6, IL8, C-reactive protein, and tumor necrosis factor-α) measured in a subgroup of survivors (n = 421). Multivariable Cox proportional hazard models with restricted cubic splines were used to investigate the relation between the EDIP score and CRC recurrence and all-cause mortality. Models were adjusted for age, sex, BMI, PAL, smoking status, stage of disease, and tumor location. RESULTS: The median follow-up time was 2.6 y (IQR: 2.1) for recurrence and 5.6 y (IQR: 3.0) for all-cause mortality, during which 154 and 239 events occurred, respectively. A nonlinear positive association between the EDIP score and recurrence and all-cause mortality was observed. For example, a more proinflammatory diet (EDIP score +0.75) compared with the median (EDIP score 0) was associated with a higher risk of CRC recurrence (HR: 1.15; 95% CI: 1.03, 1.29) and all-cause mortality (HR: 1.23; 95% CI: 1.12, 1.35). CONCLUSIONS: A more proinflammatory diet was associated with a higher risk of recurrence and all-cause mortality in CRC survivors. Further intervention studies should investigate whether a switch to a more anti-inflammatory diet improves CRC prognosis.

Bipolar disorder is characterized by recurrent mood episodes, affecting 1% to 2% of the population. Although its defining features are manic and hypomanic episodes, its course is dominated by depressive syndromes. Diagnosis can be challenging owing to symptom overlap with other disorders. Management goals include early and complete remission of acute episodes and the prevention of relapse between episodes. We present an overview of bipolar disorder and its subtypes, including algorithms and suggestions for screening, assessment, and treatment.

BACKGROUND: A subungual glomus tumour is a rare benign neoplasm that develops in the distal portion of the finger from the glomus body. Hand surgeons are most significant in the diagnosis of this tumour CASE REPORT: We present an atypical case of a patient who experienced multiple recurrences of a subungual glomus tumour of the finger over a period of 26 years. A transungual approach was used to remove the nail during the surgical excision. Postoperatively, the patient was symptom-free DISCUSSION: The glomus body is the neuromyoarterial histological structure located in the stratum reticularis of the dermis of the skin and the subungual regions. Recurrences can be classified as early, delayed and ancient. Early recurrences may result from incomplete excision or a second tumour that develops within a year of the initial excision. A year following excision, delayed recurrences are thought to be caused by a new glomus tumour at the fingertip. A tumour that reappears more than three times after excision on the same fingertip in five years can be either a new or incomplete excised tumour, as in our case, and is considered an ancient recurrence. Surgical eye loupes should be use intraoperatively to improve complete tumour lesion excision CONCLUSION: To the best of our knowledge, this is the first case of a finger with five recurrences post excision. In the event that excision-related pain is significant, recurrence should be considered. Delayed and ancient recurrences are thought to be caused by a new glomus tumour at the fingertip that one cannot prevent with surgery Level of evidence: Level 5

Background and AimsA chronic feeling of fatigue occurs in up to 85% of childhood cancer survivors (CCS). This phenomenon has a detrimental effect on quality of life, reintegration in daily life activities and psychosocial functioning of the patient. Therefore, it is important to elucidate potential individual risk and protective factors. MethodsCCS who were treated in the University Hospital of Leuven, completed two annual questionnaires on cancer-related distress (fear of cancer recurrence and post-traumatic stress, resilience and fatigue). Associations between distress and fatigue levels were examined by performing cross-lagged panel analyses. Resilience was included as a potential moderator. These models included all within-time associations, stability paths, and cross-lagged paths. Gender and time since diagnosis were included as covariates. ResultsIn total, 110 CCS participated in this study, aged 14-25 years (average time since diagnosis 12.2 years; 41.8% boys; diagnosed with leukemia/lymphoma [49%], solid tumor [15%], brain tumor [16%] or other [20%]). Fear of cancer recurrence and post-traumatic stress at baseline positively predicted fatigue 1 year later. Cross-lagged panel analyses showed that resilience did not buffer the effect of fear of cancer recurrence on fatigue, in contrary to our expectations. Stability coefficients were high for all study variables. ConclusionThis study indicates associations between cancer-related distress (fear of cancer recurrence and post-traumatic stress), resilience and cancer-related fatigue over time in CCS. Interventions to improve fatigue levels could be focusing on both tackling cancer-related distress, while improving resilience levels as well.

usc The purpose of this study was to assess the impact of a change in macroscopic/surgical margin width upon histological margins and loco-regional failure in early oral tongue squamous cell carcinoma (OTSCC). In 2009, the surgical margin protocol was increased from 10 mm to 15 mm. A retrospective review was performed of all patients who underwent treatment for early OTSCC between 2009 and 2016 with a 15-mm surgical margin (n = 142), and these patients were compared to those treated between 1999 and 2008 with a 10-mm surgical margin (n = 78). There was a significant increase in the rate of clear histological margins (P < 0.001). The rates of close (P = 0.002) and involved (P < 0.001) histological margins decreased significantly. There were significant reductions in local (P < 0.001) and regional (P < 0.001) recurrence rates. This study demonstrated that a surgical margin of 15 mm delivered significantly lower rates of close/involved histological margins and improved local and regional disease recurrence in early OTSCC when compared with a surgical margin of 10 mm. Refereed/Peer-reviewed

Current estimates suggest that a patent foramen ovale (PFO) may exist in up to 25% of the general population and is a potential risk factor for embolic, ischemic stroke. PFO closure complications include bleeding, need for procedure-related surgical intervention, pulmonary emboli, device malpositioning, new onset atrial arrhythmias, and transient atrioventricular block. Rates of PFO closure complications at a national level in the Unites States remain unknown. To address this, we performed a contemporary nationwide study using the 2016 and 2017 Nationwide Readmissions Database (NRD) to identify patterns of readmissions after percutaneous PFO closure. In conclusion, our study showed that following PFO closure, the most common complications were atrial fibrillation/atrial flutter followed by acute heart failure syndrome, supraventricular tachycardia and acute myocardial infarction.

Contains fulltext : 291760.pdf (Publisher’s version ) (Open Access) BACKGROUND: Patients with non-muscle invasive bladder cancer (NMIBC) are at a high risk of tumor recurrence. It has not been previously investigated if adherence to cancer prevention recommendations lowers the risk of recurrence. OBJECTIVES: We examined whether the standardized lifestyle score measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations was associated with the risk of recurrence and progression among patients with NMIBC. METHODS: The study population included patients diagnosed with primary NMIBC between 2014 and 2017 from the prospective cohort UroLife. Lifestyle was assessed at baseline (n = 979; reflecting the prediagnosis period) and 3-mo postdiagnosis (n = 885). The standardized 2018 WCRF/AICR score was constructed based on recommendations for body weight, physical activity, diet, and alcohol intake. We computed multivariable-adjusted HRs and 95% CIs using Cox proportional hazard regression models. RESULTS: During a median follow-up time of 3.7 y, 320 patients developed ≥1 recurrence(s) and 49 experienced progression. Patients in the highest compared with the lowest tertile of postdiagnosis WCRF/AICR scores had a lower risk of first bladder cancer recurrence (HR: 0.74; 95% CI: 0.56, 0.98). No associations were observed for multiple recurrences (HR: 0.90; 95% CI: 0.70, 1.15) or for the baseline score with either first (HR: 1.07; 95% CI: 0.82, 1.40) or multiple recurrences (HR: 1.04; 95% CI: 0.82, 1.31). Improving lifestyle after diagnosis (per 1-point increase) was not significantly associated with the risk of first or multiple recurrence(s) (HR: 0.87; 95% CI: 0.74, 1.02; HR: 0.93; 95% CI: 0.80, 1.08, respectively). No associations were observed for bladder cancer progression, but the power was limited. CONCLUSIONS: Better adherence to the WCRF/AICR cancer prevention recommendations 3 mo after NMIBC diagnosis, but not before diagnosis, is associated with a decreased risk of first bladder cancer recurrence. More studies evaluating postdiagnosis lifestyles are needed to provide solid support for lifestyle recommendations for cancer survivors. 01 april 2023

Background: The mechanism underlying the sex differences in atrial fibrillation (AF) recurrence following pulmonary vein (PV) isolation is not fully understood. We hypothesized that non-PV foci and epicardial adipose tissue (EAT) play a key role. Methods and Results: Data from 304 consecutive patients (75% males) who underwent contrast-enhanced computed tomography and catheter ablation of AF were reviewed. The EAT around the atrium was measured separately in 4 parts of the atrium. All patients underwent high-dose isoproterenol infusions to assess the non-PV foci. Significantly more non-PV foci and less EAT around the atrium were observed in female patients than in male patients. In males, those with non-PV foci on the left atrial (LA) anterior wall had significantly greater EAT for the same lesions than those without non-PV foci. During a median follow-up of 27 months, the predictors of AF recurrence after first catheter ablation were female sex, presence of non-PV foci, LA diameter, and septal EAT index. A sex-specific analysis revealed that LA diameter was a predictor only in males and that the presence of non-PV foci in the septal region was a strong predictor in males (hazard ratio [HR]: 2.24) and females (HR: 3.65). Conclusions: Sex-specific differences were observed in non-PV foci sites and local EAT and in regard to the predictors of AF recurrence.

Objective: A comprehensive overview of the surgical treatment of vulvar cancer, including recurrent forms. Methodology: A review work providing a basic overview of the pathogenesis, dia gnosis and surgical treatment of vulvar cancer with a focus on the possibilities of treatment of its recurrences. It includes an illustrative case report presenting a patient with invasive squamous cell carcinoma of the vulva with iterative local recurrences and subsequent development of tumor triplicity and distant metastatic involvement. Conclusion: Surgical treatment remains the main modality of vulvar cancer therapy, even in the case of locally advanced or recurrent findings. In these cases, multidisciplinary cooperation of operational fields is necessary. The discipline of treated patients with participation in regular dispensary care plays an important role in the early detection of recurrences. (Chemo)radiotherapy remains a possible alternative to the surgical solution; in clinical practice, radiotherapy has an irreplaceable place in adjuvant therapy. Regional and distant recurrences are characterized by a poor prognosis. Key words: vulvar cancer – surgery – local recurrence – groin (inguinal) recurrence – distant recurrence – chemoradiotherapy

PURPOSE The aim of the randomized trial, UKALL2003, was to adjust treatment intensity on the basis of minimal residual disease (MRD) stratification for children and young adults with acute lymphoblastic leukemia. We analyzed the 10-year randomized outcomes and the time for patients to be considered cured (ClinicalTrials.gov identifier: NCT00222612 ). METHODS A total of 3,113 patients were analyzed including 1,054 patients who underwent random assignment (521 MRD low-risk and 533 MRD high-risk patients). Time to cure was defined as the point at which the chance of relapse was < 1%. The median follow-up time was 10.98 (interquartile range, 9.19-13.02) years, and survival rates are quoted at 10 years. RESULTS In the low-risk group, the event-free survival was 91.7% (95% CI, 87.4 to 94.6) with one course of delayed intensification versus 93.7% (95% CI, 89.9 to 96.1) with two delayed intensifications (adjusted hazard ratio, 0.73; 95% CI, 0.38 to 1.40; P = .3). In the high-risk group, the event-free survival was 82.1% (95% CI, 76.9 to 86.2) with standard therapy versus 87.1% (95% CI, 82.4 to 90.6) with augmented therapy (adjusted hazard ratio, 0.68; 95% CI, 0.44 to 1.06; P = .09). Cytogenetic high-risk patients treated on augmented therapy had a lower relapse risk (22.1%; 95% CI, 15.1 to 31.6) versus standard therapy (52.4%; 95% CI, 28.9 to 80.1; P = .016). The initial risk of relapse differed significantly by sex, age, MRD, and genetics, but the risk of relapse for all subgroups quickly coalesced at around 6 years after diagnosis. CONCLUSION Long-term outcomes of the UKALL2003 trial confirm that low-risk patients can safely de-escalate therapy, while intensified therapy benefits patients with high-risk cytogenetics. Regardless of prognosis, the time to cure is similar across risk groups. This will facilitate communication to patients and families who pose the question “When am I/is my child cured?”

Until recently, most modern neuroscience research on addiction using animal models did not incorporate manipulations of social factors. Social factors play a critical role in human addiction: social isolation and exclusion can promote drug use and relapse, while social connections and inclusion tend to be protective. Here, we discuss the state of the literature on social factors in animal models of opioid and psychostimulant preference, self-administration, and relapse. We first summarize results from rodent studies on behavioral, pharmacological, and circuit mechanisms of the protective effect of traditional experimenter-controlled social interaction procedures on opioid and psychostimulant conditioned place preference, self-administration, and relapse. Next, we summarize behavioral and brain-mechanism results from studies using newer operant social-interaction procedures that inhibit opioid and psychostimulant self-administration and relapse. We conclude by discussing how the reviewed studies point to future directions for the addiction field and other neuroscience and psychiatric fields, and their implications for mechanistic understanding of addiction and development of new treatments.SIGNIFICANCE STATEMENTIn this review, we propose that incorporating social factors into modern neuroscience research on addiction could improve mechanistic accounts of addiction and help close gaps in translating discovery to treatment. We first summarize rodent studies on behavioral, pharmacological, and circuit mechanisms of the protective effect of both traditional experimenter-controlled and newer operant social-interaction procedures. We then discuss potential future directions and clinical implications.

Refractory cytomegalovirus reactivation (RCR) after allo-hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes. Current studies for the risk factors and survival of patients with post-transplantation RCR remain limited.163 patients with Cytomegalovirus (CMV) reactivation undergoing allo-HSCT in Jiangsu Province hospital from Jan 2013 to Dec 2020 were analyzed retrospectively.Multivariate analysis revealed that highest CMV viremia1 × 10Factors such as higher viral load, thrombocytopenia, and ATG used in conditioning therapy increased the incidence of RCR. Patients with RCR had worse NRM, OS, and RFS within 100 days after transplantation.

The optimal timing of operative management in children with primary spontaneous pneumothorax (PSP) remains controversial. This study sought to determine early risk factors for failure of chest tube nonoperative management during the initial hospitalization in adolescents with PSP.A retrospective review was conducted for children (aged ≤18 years) admitted to a single tertiary care referral center for their first presentation of a PSP managed with at least 48 h of chest tube decompression (CTD) alone. Patient outcomes and early risk factors for operative management were analyzed by multivariate regression.Of the 39 patients who met inclusion criteria, 15 (38.5%) patients failed nonoperative treatment while 24 (61.5%) patients were managed with CTD therapy alone. Progression to thoracoscopic surgery was associated with longer CTD of 8 vs 3 days and hospital length of stay of 9 vs 4 days when compared to nonoperative management (p 0.001, both). Air leak and increase in pneumothorax size at 24 h after CTD were independently associated with progression to surgery (p = 0.007, p = 0.002). Combined, these risk factors were associated with a significant increase in recurrence (OR 6.00, 95% CI 1.11-41.11, p = 0.048). There were no significant differences between PSP management strategies regarding cumulative radiation exposure or 2 year recurrence.Air leak or increasing pneumothorax size within 24 h of CTD are highly correlated with failed nonoperative management during the initial hospitalization in pediatric patients with PSP. This data may be useful in the development of pediatric-specific treatment algorithms to optimally manage these patients.Treatment study, Level III.

Cancer outcomes with chemotherapy are inferior in patients of minority racial/ethnic groups and those with obesity. Chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for relapsed/refractory hematologic malignancies, but whether its benefits extend commensurately to racial/ethnic minorities and patients with obesity is poorly understood. With a primary focus on patients with B-cell acute lymphoblastic leukemia (B-ALL), we retrospectively evaluated the impact of demographics and obesity on CAR T-cell therapy outcomes in adult and pediatric patients with hematologic malignancies treated with CAR T-cell therapy across 5 phase 1 clinical trials at the National Cancer Institute from 2012 to 2021. Among 139 B-ALL CAR T-cell infusions, 28.8% of patients were Hispanic, 3.6% were Black, and 29.5% were overweight/obese. No significant associations were found between race, ethnicity, or body mass index (BMI) and complete remission rates, neurotoxicity, or overall survival. Hispanic patients were more likely to experience severe cytokine release syndrome compared with White non-Hispanic patients even after adjusting for leukemia disease burden and age (odds ratio, 4.5; P = .001). A descriptive analysis of patients with multiple myeloma (n = 24) and non-Hodgkin lymphoma (n = 23) displayed a similar pattern to the B-ALL cohort. Our findings suggest CAR T-cell therapy may provide substantial benefit across a range of demographics characteristics, including for those populations who are at higher risk for chemotherapy resistance and relapse. However, toxicity profiles may vary. Therefore, efforts to improve access to CAR therapy for underrepresented populations and elucidate mechanisms of differential toxicity among demographic groups should be prioritized.

Bevacizumab and chemotherapy are used in glioblastoma multiforme (GBM) relapse. However, the choice of chemotherapeutic agent remains an open question and this study aimed to evaluate the efficacy and safety of different combinations.Between June 2005 and August 2020, all patients treated with chemotherapy plus bevacizumab (BVZ) for recurrent glioblastoma in the Georges-François Leclerc Cancer Center, Dijon, France were included in this retrospective comparative study. The primary objective was progression-free survival (PFS) and as secondary objectives, overall survival (OS), disease control rate (DCR), and safety were investigated. Factors associated with response were also analyzed.A total of 160 patients were screened: 100 received fotemustine plus BVZ (62%) and 62 (38%) received another cytotoxic agent plus BVZ: 35 (22%) irinotecan (IRI), 18 (11%) temozolomide (TEM), and 7 (4%) lomustine (LOM). In the whole population, median PFS was 4.47 months, median OS was 9 months, and 3-month DCR was 51%. Regarding survival according to treatment, median OS was significantly lower in the fotemustine group compared to that in other cytotoxic agents: 7.3 vs. 19.9 months. In the fotemustine group, steroids use at baseline and low Karnofsky performance status were associated with poor median OS. Grade 3-4 adverse events were found in 21.9%, with no difference between groups, but 7 patients had grade 5 adverse events in the fotemustine group.Using real-life data, this study showed lower efficacy of fotemustine and bevacizumab, as compared to IRI or TEM or LOM-BVZ combinations.

Postoperative skeletal relapse is the most important issue in patients undergoing orthognathic surgery. This study aimed to investigate clinical skeletal relapse (≥2 mm) after mandibular setback surgery (intraoral vertical ramus osteotomy: IVRO) using receiver operating characteristic curve (ROC curve) analysis.Serial cephalograms of 40 patients with mandibular prognathism were obtained at different time points: (1) before surgery (T1), (2) immediately after surgery (T2), and (3) at least with a 2-year follow-up postoperatively (T3). The menton (Me) was used as the landmark for measuring the amount of mandibular setback and postoperative skeletal relapse. Postoperative stability (T32) was divided into groups A and B by skeletal relapse ≥2 mm and2 mm, respectively. The area under the ROC curve (AUC) was used to determine the cut-off point for mandibular setback.At the immediate surgical setback (T21), the amount of setback in group A (15.55 mm) was significantly larger than in group B (10.97 mm). Group A (T32) showed a significant relapse (4.07 mm), while group B showed a significant posterior drift (1.23 mm). The amount of setback had the highest AUC area (0.788). The cut-off point was 14.1 mm (T21) that would lead to a clinical relapse of 2 mm (T32).In IVRO, the postoperative mandibular positions reveal posterior drift and anterior displacement (relapse). The experience of clinical observation and patient perception of postoperative skeletal relapse was ≥2 mm. In the ROC curve analysis, the cut-off point of setback was 14.1 mm.

Relapse after orthodontic treatment is a major clinical issue in the dental field. Studies indicate that simvastatin may, to some extent, decrease the rate and magnitude of relapse status. Recent evidence demonstrated that exosome-based drug delivery has a broad prospect of clinical application. Hence, this study investigates whether simvastatin encapsulated in exosomes can inhibit relapse after orthodontic tooth movement (OTM).Periodontal ligament stem cells (PDLSCs) and their exosomes (PDLSCs-Exo) were isolated and identified. Exosomal simvastatin was obtained by co-incubation of simvastatin and PDLSCs-Exo. An OTM rat model was established. During the relapse period, rats' local alveolar bone was injected with simvastatin, PDLSCs-Exo, and exosomal simvastatin to examine the effect on relapse. Finally, we analyzed the influence of exosomal simvastatin on osteogenesis at the molecular and histologic levels.PDLSCs and PDLSCs-Exo were successfully extracted and characterized by multiple means. Simvastatin encapsulated in exosomes can increase the solubility of the drug. Exosomal simvastatin can enhance its inhibition of relapse after OTM in the rat model. The expression level of osteogenic-related genes and proteins in the exosomal simvastatin group is higher than in other groups. Histologic analysis showed a reduction of bone-resorptive lacunae in the exosomal simvastatin group.Encapsulating simvastatin into the exosomes derived from PDLSCs can improve simvastatin solubility and enhance the inhibition effect of relapse in the rat model of OTM. Notably, local injection of PDLSCs-Exo alone can also block the relapse after OTM.

Introduction To investigate the current experience of the ARM-Net Consortium in the management of epididymo-orchitis (EO) in patients with anorectal malformations (ARMs), and to identify specific risk factors and the need for urological care involvement. Materials and Methods We retrospectively collected data of EO in patients with ARM between 2015 and 2019. Data on urological aspects, ARM type, surgical approach, associated anomalies, diagnosis, and treatment of EO were collected and analyzed. Results Twenty-nine patients were reported by 12 centers. Twenty-six patients with EO (90%) had ARM with a rectourinary fistula. Median age at first EO was 2 years (range: 15 days–27 years). Twenty patients (69%) experienced multiple EO, and 60% of recurrences were ipsilateral. Associated urological anomalies included vesicoureteral reflux (48%), urethral anomalies (41%), neurogenic bladder (41%), and ectopic vas (10%). A positive urine culture during EO was present in 69%. EO was treated with antibiotics (90%), limiting surgical exploration to 14%. Prevention of recurrences included surgery (bulking agents 15%, vasectomy 15%, and orchiectomy 5%) and antibiotic prophylaxis (20%). Conclusion Urologists may encounter patients with EO in ARM patients, frequently with positive urine culture. An appropriate urologic work-up for most ARM patients is necessary to identify and treat underlying risk factors. A practical scheme for the work-up is suggested for a close collaboration between pediatric surgeons and urologists.

The aim of this study was to evaluate the osteolysis rate, graft remodeling, and risk factors for osteolysis at the 1-year threshold after an arthroscopic Latarjet procedure with double-button fixation.In this multicenter, retrospective study, postoperative computed tomography scans obtained after an arthroscopic Latarjet procedure with double-button fixation to treat anterior shoulder instability were analyzed at 15 days and at 3, 6, and 12 months. Graft volume, dimensions, and morphologic remodeling were analyzed.Twenty-seven patients were included (mean age, 26 years). At 1 year, osteolysis occurred in 19 of 27 patients (70%). The volume initially decreased until 6 months' follow-up (-35%; range, -75% to +26%) and then increased until our last follow-up. At 1 year, the graft volume decreased by 17% (range, -61% to +56%) compared with the immediate postoperative volume. In multivariate analysis, the rate of osteolysis was inversely associated with an unhealed graft at 3 months (P = .02; β coefficient = -44.50 [95% confidence interval, -81 to -8]). The maximal height of the graft significantly grew 0.2 cm (range, -55 to +124 mm) (P = .015). In the sagittal plane, osteolysis occurred in the superior part in 100% of patients (27 of 27) whereas bone formation occurred in the inferior part. In the axial plane, osteolysis occurred in the anterior part whereas bone formation occurred in the posterior part. In the articular part, the observed remodeling was aimed to obtain a new anatomic and congruent glenoid.At 1 year after an arthroscopic Latarjet procedure with double-button fixation, osteolysis occurred in 70% of patients. The rate of osteolysis was 17% of the initial volume. Osteolysis occurred mainly during the first 6 months, in the anterior and superior parts. Remodeling led to a circular anatomic glenoid. This osteolysis did not cause any recurrence of instability or require revision surgery.

This qualitative study was carried out with 10 dyads of patients-family members to explore their perception about psychotic relapses. Data were collected through a semi-structured interview from April to August 2019, in Brazil, and analyzed using the thematic analysis proposed by BraunClark. Four main themes emerged from the interviews: (1) defining and describing the psychotic relapses; (2) risk factors for psychotic relapse; (3) protective factors for psychotic relapse; and (4) early warning signs: identification of an episode of psychotic relapse. Exploring the perception of patients with psychotic disorders and their families about relapse is fundamental for the development of relapse risk assessment tools and to guide further research on this topic.

Vitamin D (VitD) maintains bone health and may influence orthodontic tooth movement (OTM). The objective was to evaluate the VitD effect on bone morphometry and the rate and stability of OTM.Thirty-two male Sprague Dawley rats were assigned into 2 experimental groups, treated with VitD by gavage (systemic) or injection (local), and 2 respective control groups treated with phosphate-buffered saline for 47 days. OTM was performed for 7 days with a nickel-titanium coil bonded between the maxillary first molar and incisors. Microcomputed tomography scanning was performed at 5 time points: before administration of VitD, the start of OTM, the end of OTM, 7 days post-OTM, and 30 days post-OTM. The rate and stability of OTM were assessed. Bone morphometry was analyzed by bone mineral density, bone volume/total volume, total porosity, trabecular pattern factor, structure model index, and connectivity density.The systemic VitD group showed a lower OTM rate and a lower relapse than the control (P 0.05). It also demonstrated increased bone mineral density, bone volume/total volume, and a decrease in total porosity (P 0.05). The bone structure appeared more fragmented and presented a lower connectivity density than the control (P 0.05). No statistical difference was found between VitD local administration and the other groups for the rate and stability of OTM or bone morphometry.The systemic administration of VitD caused a decrease in the OTM rate by generating more bone resistance but also contributed to a lower relapse with a higher bone mineral density.

Atrial low voltage area (LVA) catheter ablation has emerged as a promising strategy for ablation of persistent atrial fibrillation (AF). It is unclear if catheter ablation of atrial LVA increases treatment success rates in patients with persistent AF.The primary aim of this trial is to assess the potential benefit of adjunctive catheter ablation of atrial LVA in addition to pulmonary vein isolation (PVI) in patients with persistent AF, when compared to PVI alone. The secondary aims are to evaluate safety outcomes, the quality of life and the healthcare resource utilization.A multicenter, prospective, parallel-group, 2-arm, single-blinded randomized controlled trial is under way (NCT03347227). Patients who are candidates for catheter ablation for persistent AF will be randomly assigned (1:1) to either PVI alone or PVI + atrial LVA ablation. The primary outcome is 18-month documented event rate of atrial arrhythmia (AF, atrial tachycardia or atrial flutter) post catheter ablation. Secondary outcomes include procedure-related complications, freedom from atrial arrhythmia at 12 months, AF burden, need for emergency department visits/hospitalization, need for repeat ablation for atrial arrhythmia, quality of life at 12 and 18 months, ablation time, and procedure duration.Characterization of Arrhythmia Mechanism to Ablate Atrial Fibrillation (COAST-AF) is a multicenter randomized trial evaluating ablation strategies for catheter ablation. We hypothesize that catheter ablation of atrial LVA in addition to PVI will result in higher procedural success rates when compared to PVI alone in patients with persistent AF.

The aim of this study was to evaluate postoperative relapse after the surgical correction of skeletal Class III deformities of various facial patterns as a guide to surgical planning. A retrospective cohort study of 90 consecutive patients with skeletal Class III malocclusion who underwent bimaxillary surgery was performed. The surgical outcomes and postoperative stability were compared. The primary predictor variable was vertical facial type, which was classified into three groups according to the Frankfort mandibular plane angle (FMA). The primary outcome of angular and linear measurements was obtained using serial cone beam computed tomography scans obtained at time points of preoperative, 1 week after surgery, and orthodontic debonding. No significant difference in skeletal relapse was observed in patients with the different vertical facial types. The mandible displayed a forward and upward relapse in all three groups postoperatively. The patients with a low FMA exhibited a more consistent mandibular relapse pattern than those with a normal or high FMA. These findings suggest that bimaxillary surgery is clinically stable for mandibular prognathism regardless of the vertical facial pattern. However, 1-1.5 mm of overcorrection in the mandible setback should be considered in patients with a low FMA, because of the greater facial depth and consistent forward and upward mandibular relapse pattern.

Relapse after first-episode psychosis (FEP) is a major clinical challenge for specialized early intervention services. Understanding patient perspectives on factors contributing to relapse can inform the development of risk assessments and preventive interventions. The objective of this study was to identify factors that may contribute to and prevent relapse from the perspectives of patients receiving services for FEP. Data from 25 participants across four focus groups in Canada were analyzed with a descriptive content analysis approach. Twelve factors were identified, of which four (social environment, technology use, medication, and lifestyle behaviors) had both contributory and preventive roles. In descending order of frequency, risk factors for relapse included substance use; unsupportive social environment; technology use; taking and not taking medication; lack of sleep; work, career, or school stress; significant life events; symptoms of depression or mania; generalized worry; and financial stress. Preventive factors consisted of having a supportive social environment, using technology, taking medication, using coping strategies, and engaging in healthy lifestyle behaviors and meaningful activities. These findings extend the literature on relapse vulnerability and protective factors. Importantly, the factors identified in this study are modifiable, and thereby provide insights for the development and optimization of relapse risk assessments and preventive interventions.

Summary Aim of the study Nomograms have been proposed to assess prognosis following curative surgery for gastric cancer. The objective of the current study was to evaluate the performance of the Gastric Cancer Collaborative Group nomograms developed in 2014 by Kim et al., using a cohort of patients from a 10-year single institution experience in gastric cancer management. Patients and methods We retrospectively reviewed patients who underwent curative-intent surgery for histologically confirmed gastric cancer at First Surgical Clinic of Padua University Hospital (Italy) from January 2010 to May 2020. Univariable and multivariable Cox proportional hazard models were employed to assess the effect of the variables of interest on mortality and recurrence. Multivariable analysis was performed by considering the variables included in the Gastric Cancer Collaborative Group nomograms in order to validate them. The performance of the nomograms was evaluated using Harrell's C-index and calibration plots. Results Overall, 168 patients were included, with a median follow-up of 20.1 months. On multivariable analysis, tumor location, lymph node ratio, and pathological T stage were associated with recurrence; age, tumor location, lymph node ratio, and pT stage were associated with OS (overall survival). The nomograms had good discriminatory capability to classify both OS (C-index: 0.75) and DFS (disease-free survival) (C-index 0.72). The corrected C-Index for DFS based on the AJCC staging system revealed better prediction (C-Index 0.75), while the corrected C-Index for OS had worse discrimination ability compared with the current nomogram (C-Index 0.72). Conclusions The Gastric Cancer Collaborative Group nomograms demonstrated good performances in terms of prediction of both OS and DFS on external validation. The two nomograms are easy to apply, and variables included are widely available to most facilities.

It is believed that acute pancreatitis (AP), recurrent AP (RAP) and chronic pancreatitis (CP) represent stages of the same disease spectrum. We aimed to identify risk factors, clinical presentation and outcomes in patients with prior RAP who develop CP.We retrospectively reviewed patients with CP who were seen at our Pancreas Center during 2016-2021. We divided them into two groups: with and without RAP (≥2 episodes of AP). We compared demographics, clinical presentation and resource utilization between the two groups.We identified 440 patients with CP, of which 283 (64%) patients had preceding RAP. These patients were younger (55.6 vs 63.1 years), active smokers (36% vs 20%) and had alcohol-related CP (49% vs 25%) compared to those without RAP and CP (p 0.05). More patients with RAP had chronic abdominal pain (89% vs 67.9%), nausea (43.3% vs 27.1%) and exocrine pancreatic insufficiency (65.8% vs 46.5%) (p 0.05). More patients with RAP used opioids (58.4% vs 32.3%) and gabapentinoids (56.6% vs 34.8%) (p 0.05). They also had more ED visits resulting in an opioid prescription (9.68% vs 2%) and more CP flares requiring hospitalization (3.09 vs 0.87) (p 0.05).Young age, smoking and alcohol use are seen in patients with RAP who progress to CP. These patients are highly symptomatic and use more healthcare resources, suggestive of an overall a more course compared to those patients who develop CP without preceding RAP. Early identification and counselling of these patients may slow down progression to CP.

Long-acting injectable antipsychotics (LAIs) have been shown to reduce acute episodes of schizophrenia spectrum disorders (SSDs). However, breakthrough relapses are frequent, possibly because of underdosing in clinical practice. In this framework, the advantages of therapeutic drug monitoring (TDM) may be overlooked. This study explored the association of low steady-state LAI levels with a higher risk of relapse in SSDs, despite the use of a licensed posology.Forty-eight clinically stable outpatients with SSD underwent LAI-TDM using liquid chromatography-mass spectrometry for routine observational purposes. Baseline anamnestic, pharmacological, and psychometric evaluations compared subjects with "under-range" versus "in-range" LAI serum levels; between-group comparisons for different LAI treatments were also performed. A binary logistic regression explored which baseline factors (age, sex, previous hospitalizations, psychopathology, specific LAI treatment, and underrange serum levels) predicted relapse during the next 12 months.Baseline comparisons did not show significant between-group differences, except for a higher percentage of underrange values in individuals receiving olanzapine pamoate. A total of 10 patients (20.8%) relapsed during the follow-up; only underrange LAI levels predicted the event (odds ratio 0.03, 95% confidence interval 0.01-0.36; P = 0.005).Even if relapse remains as a multifactorial event, LAI-TDM may identify subjects at risk for this negative outcome, thus optimizing antipsychotic maintenance treatment in the context of precision medicine. The finding of underrange LAI plasma levels in real-world practice should prompt adequate monitoring of clinically stable outpatients to identify the early signs of psychopathological deterioration.

Chronic alcohol intake down-regulates GABAergic transmission and reduces levels of neuroactive steroids. These changes are associated with greater stress dysregulation and high alcohol craving which in turn increases relapse risk.This study tested whether potentiation of the neurosteroid system with pregnenolone (PREG), a precursor to neuroactive steroids and known to increase GABAergic transmission, will normalize chronic alcohol-related stress adaptations in the hypothalamic-pituitary-adrenal (HPA) axis and autonomic responses and reduce alcohol craving to significantly impact relapse risk.Forty-three treatment-seeking individuals with alcohol use disorder (AUD) were randomized to placebo (PBO) or supraphysiologic pregnenolone doses of 300 mg or 500 mg treatment using a parallel-between subject design as part of a larger 8-week pilot clinical trial. In week 2, they participated in a 3-day laboratory experiment where on each day they self-administered the assigned study drug in the laboratory and were then exposed to 5-min personalized guided imagery provocation of stress, alcohol, or neutral/relaxing cues, one condition per day on separate days, in a random, counterbalanced order. Repeated assessments of alcohol craving, anxiety, HPA axis, heart rate (HR), systolic (SBP), and diastolic blood pressure (DBP) and serum pregnenolone levels were made on each day.Pregnenolone levels were significantly increased in the PREG groups versus PBO. PREG treatment decreased stress- and alcohol cue- induced craving and dose-specifically reduced stress-induced anxiety in the 300 mg/day group. Both PREG doses compared to PBO also normalized CORT/ACTH and increased stress-induced HR, stress- and cue-induced SBP, and in the 300 mg PREG group cue-induced DBP responses relative to neutral condition.Findings indicate that pregnenolone decreases stress- and alcohol cue-provoked craving and normalizes HPA axis and autonomic arousal in individuals with AUD, thereby supporting the need for further assessment of pregnenolone in the treatment of AUD.

Aim: Bascom's cleft-lift procedure for pilonidal sinus disease under tumescent local analgesia is feasible and well tolerated with favourable short-term outcomes. We aimed to assess the 10-year treatment success rate after cleft-lift under tumescent local analgesia. Method: This was a single-centre cohort study based on prospectively registered perioperative data and survey data with additional data from electronic medical records. The cleft-lift procedure was performed under tumescent local analgesia in a day-surgical setting at a tertiary referral hospital between 1 July 2008 and 31 March 2014. The primary outcome was the 10-year risk treatment success defined as complete wound healing within 180 days of surgery or no recurrence assessed with competing risk analyses. Secondary outcomes were time to complete wound healing, persistent pain and cosmetic satisfaction. Results: Two hundred patients with complex pilonidal sinus disease were included. Indication was incomplete wound healing after pilonidal sinus surgery in 43 (21.5%) patients, recurrence after previous intervention in 78 (39.0%) or moderate to complex sinuses assessed by a consultant surgeon in 79 (39.5%). One hundred and ninety-five patients had complete wound healing within 180 days with a median time of 29 days (interquartile range 16–47). The cumulative risk of 10-year recurrence was 11.3% (95% CI 6.2%–16.4%) with a median follow-up time of 8.5 (1.0–10.7) years. Treatment success was 86.1% (95% CI 80.6%–91.5%). No significant predictors were associated with recurrence, and 90% of patients experienced no persistent pain. Conclusion: Cleft-lift performed under tumescent local analgesia has an acceptable 10-year treatment failure rate, making the method feasible in a day-surgery setting.

Purpose: Surgical interventions tend to have an effect on the generation of recurrences in tumor patients due to the anesthesia involved as well as tissue damage and subsequent inflammation. This can also be found in patients with breast cancer. Methods: In this multicenter study, we investigated data of 632 patients with breast cancer and the subsequent diagnosis of a recurrence. The patient data were acquired from 1 January 2006 to 31 December 2019 in eight different centers in Germany. The data sets were separated into those with primary surgery, primary systemic therapy with subsequent surgery, and reconstructive surgery. Three different starting points for observation were defined: the date of diagnosis, the date of first surgery, and the date of reconstructive surgery, if applicable. The observational period was divided into steps of six months and maxima of recurrences were compared. Furthermore, the variance was calculated using the difference of the distribution in percent. Results: The descriptive analysis showed no resemblance between the groups. The variance of the difference of the recurrence rates analysis using the surgical date as the starting point showed similarities in the age subgroup. Conclusion: Our clinical analysis shows different metastatic behavior in different analysis and treatment regimes. These findings justify further investigations on a larger database. These results may possibly identify an improved follow-up setting depending on tumor stage, biology, treatment, and patient factors (i.e., age, …).

Historically, Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has been associated with poor outcomes, and allogeneic hematopoietic cell transplantation (allo-HCT) is recommended in first complete remission (CR1). However, in the tyrosine kinase inhibitor (TKI) era, rapid attainment of a complete molecular remission (CMR) is associated with excellent outcomes without allo-HCT, suggesting transplant may not be required for these patients. To test this hypothesis, we retrospectively identified adult patients with Ph+ ALL treated with induction therapy, including TKIs, and attained CMR within 90 days of diagnosis at 5 transplant centers in the United States. We compared outcomes of those who did and did not receive allo-HCT in first remission. We identified 230 patients (allo-HCT: 98; non-HCT: 132). The allo-HCT cohort was younger with better performance status. On multivariable analysis (MVA), allo-HCT was not associated with improved overall survival (adjusted hazard ratio [aHR]: 1.05; 95% CI, 0.63-1.73) or relapse-free survival (aHR: 0.86; 95% CI, 0.54-1.37) compared with non-HCT treatment. Allo-HCT was associated with a lower cumulative incidence of relapse (aHR: 0.32; 95% CI, 0.17-0.62) but higher non-relapse mortality (aHR: 2.59; 95% CI, 1.37-4.89). Propensity score matching analysis confirmed results of MVA. Comparison of reduced-intensity HCT to non-HCT showed no statistically significant difference in any of the above endpoints. In conclusion, adult patients with Ph+ ALL who achieved CMR within 90 days of starting treatment did not derive a survival benefit from allo-HCT in CR1 in this retrospective study.

Objective Early recurrence (ER) after pulmonary vein isolation (PVI) for atrial fibrillation (AF) is expected to resolve within the recommended 3-month blanking period, irrespective of the ablation device used. To compare the occurrence and relationship of AF within the blanking period and subsequent late recurrence (LR) with radiofrequency (RF) and cryoballoon (CB) ablation. Methods A retrospective analysis of 294 patients (mean age=62±9, 70.0% male) undergoing PVI for drug-refractory paroxysmal AF was done. After categorizing the patients into the RF group (n=152) and the CB group (n=142), a group-wise comparison was done to investigate the impact of ER on LR throughout a 2-year follow-up. Results The groups were similar regarding the occurrence of ER (RF=22.4%, CB=24.6%, p=0.62), while LR was significantly higher in the RF group (p=0.003). ER was associated with LR in the RF group (p0.01) but not in the CB group (p=0.08), while a significant independent association with an increased LR risk was observed [hazard ratio (HR) 6.12; 95% confidence interval (CI) 3.56-10.51, p0.01]. RF ablation also significantly increased the risk of LR (HR=2.93; 95% CI=1.64-5.23, p0.01). Conclusion A recurrence of atrial arrhythmia is more frequent with RF-PVI than with CB-PVI for patients with paroxysmal AF. ER and RF-ablation are strong predictors for LR after the 3-month blanking period.