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BACKGROUND: Triptans revolutionized the acute treatment of migraine; however, varied responses to triptans, as a result of poor efficacy and tolerability, are reported. A standardized definition of triptan non-response was recently proposed by the European Headache Federation (EHF). There is currently limited data available on the prevalence of triptan non-response. METHODS: We used clinic letters over a two-year duration to evaluate the triptan response and triptan efficacy or tolerability failure, or both, in a London-based tertiary headache service. RESULTS: In total, 419 adult migraine patients (females: 83.8%, age: 46 ± 18 years, chronic migraine: 88.5%) were included in a service evaluation. In line with the EHF definitions, "triptan non-response" was seen in 63.8% of patients (264/414), whereas 37.7% of patients (156/414) had failed at least two triptans (EHF "triptan resistant") and 4.6% of patients (19/414) had failed at least three triptans, including a subcutaneous formulation (EHF "triptan refractory"). Notably, 21.3% of patients (88/414) had failed at least three triptans inclusive and exclusive of subcutaneous triptan use. Advancing age (p < 0.001) and the presence of medication overuse (p = 0.006) increased the probability of triptan response, whereas an increased number of failed preventives (p < 0.001) and the use of calcitonin gene-related peptide monoclonal antibodies (p = 0.022) increased the probability of triptan non-response. The largest proportion of patients responded to eletriptan (49.5%), followed by nasal zolmitriptan (44.4%) and rizatriptan (35.7%). CONCLUSIONS: Our findings highlight an alarming prevalence of triptan non-response among adult migraineurs receiving treatment in a London-based tertiary headache service. It is imperative for clinicians to explore methods to optimize acute medication efficacy, whether this comprises changing to a triptan with a superior response rate, advocating for early intervention or considering alternative acute medication classes, such as gepants or ditans.

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Utilizing fresh distal tibia allograft in anterior glenoid reconstruction has emerged as a highly advantageous approach in addressing instances of failed anterior shoulder stabilization with glenoid bone loss. This procedure offers several benefits, including the absence of donor-site morbidity, restoration of significant glenoid defects, reestablishment of joint congruity with the humeral head, restoration of glenoid biomechanics, and the addition of cartilage to the glenoid. Furthermore, it provides a robust and reliable alternative for managing failed stabilization procedures, leading to improved clinical outcomes and a high graft healing rate, while maintaining a low occurrence of recurrent instability.

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Recurrent posterior shoulder instability after primary repair is uncommon, but presents a challenging clinical scenario. Most revisions in failed labral repair were associated with glenoid bone morphology related to critical bone loss, retroversion, or dysplasia. A variety of treatment options exist which include revision labral repair with or without capsular plication, glenoid osteotomy, humeral rotational osteotomy, or glenoid bone augmentation. No single technique has been shown to be superior and each technique has strengths and limitations. Therefore, thoughtful evaluation and planning is critical to address each patient's individual pathology to maximize success after revision surgery.

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BACKGROUND: In the last 3 decades, laparoscopic Heller myotomy (LHM) has represented the treatment of choice for esophageal achalasia, solving symptoms in most patients. Little is known about the fate of patients relapsing after LHM or their treatment. In this study, we aimed at evaluating the results of complementary pneumatic dilations (CPDs) after ineffective LHM. METHODS: We evaluated the patients who underwent LHM with Dor fundoplication (LHD) from 1992 to 2022 and were submitted to CPD for persistent or recurrent symptoms. The patients were followed clinically and with manometry, barium swallow, and endoscopy when necessary. An Eckardt score (ES) of > 3 was used as threshold for failure. RESULTS: Of 1420 patients undergoing LHD, 120 (8.4%) were considered failures and were offered CPD. Ten patients refused further treatment; in 5 CPD was not indicated for severe esophagitis; 1 patient had surgery for a misshaped fundoplication and 1 patient developed cancer 2 years after LHD; that leaves 103 patients who underwent a median 2 CPDs (IQR, 1-3), at a median of 15 (IQR, 8-36) months after surgery, with 3.0- to 4.0-cm Rigiflex dilator (Boston Scientific, Massachusetts, USA). No perforations were recorded. Only 6 patients were lost to follow-up. Thus, 97 were followed for a median of 37 months (IQR, 6-112) after the last CPD: 70 (72%) were asymptomatic, whereas 27 (28%) had significant persistent dysphagia (ES > 3). The only differences between the 2 groups were the ES after surgery (P < .01) and the number of required CPD. Overall, the combination of LHD + CPD provided a satisfactory outcome in 96.5% of the patients. CONCLUSION: CPDs represent an effective and safe option to treat patients after a failed LHD: when the postsurgery ES consistently remains high and the number of CPDs required to control symptoms exceeds 2, this may suggest the need for further invasive treatments.

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Survival rates for allografts have improved over the last 2 decades, yet failing allografts remains a challenge in the field of transplant. The risks of mortality and morbidity associated with failed allografts are compounded by infectious complications and metabolic abnormalities, emphasizing the need for a standardized approach to management. Management of failing allografts lacks consensus, highlighting the need for unified protocols to guide treatment protocols and minimize risks with postdialysis initiation. The decision to wean off immunosuppression depends on various factors, including living donor availability and infectious risks, necessitating improved coordination of care and a standard guideline. Treatment of failed pancreas focuses on glycemic control, with insulin as the mainstay, while considering surgical interventions such as graft pancreatectomy in advanced symptomatic cases. Navigating the complexities of failed allograft management demands a multidisciplinary approach and standardized stepwise protocol. Addressing the gaps in management plans for failing allografts and employing a systematic approach to transplant decisions will enhance patient outcomes and facilitate informed decision-making.

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Intussusception is a common surgical emergency in children. Clinical suspicion and radiological evaluation confirm the diagnosis of the disease. Enema reduction is the first line of management. This study aimed to explore the risk factors associated with enema reduction failure. A retrospective analysis of patients diagnosed with intussusception at three different hospitals in different countries from January 2016 to December 2022. Data collected included demographics, presenting symptoms, duration of symptoms, management, outcomes, and follow-ups. A total of 290 cases of intussusception were included in the study. Ages ranged from 1 to 36 months, with a median age of 15 months. All children underwent an enema reduction which was successful in 92.4%. Failure of reduction was seen in 16.7% of females compared to 6.4% of males, and it was significantly seen in children below the age of 1 year compared to older children. Failure of reduction significantly increases with the duration of symptoms and in children who present with bilious vomiting and currant jelly stool. In conclusion, Failure of enema reduction was more prevalent in females, in children below the age of 1 year and who present late, as well as children who had bilious vomiting and currant jelly stool. This study identified several risk factors associated with failed enema reduction in children with intussusception. Recognizing the risk factors can help guide clinicians in the management and anticipation of outcomes.

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OBJECTIVES: To investigate the risk factors and adverse prognosis associated with initial non-invasive ventilation (NIV) failure in very low birth weight infants (VLBWI) with gestational age <32 weeks. METHODS: A retrospective collection of clinical data from preterm infants admitted to the neonatal intensive care unit (NICU) in 28 tertiary hospitals in Jiangsu Province from January 2019 to December 2021 was conducted. Based on the outcomes of initial NIV, the infants were divided into a successful group and a failure group to analyze the risk factors for NIV failure and adverse prognosis. RESULTS: A total of 817 infants were included, with 453 males (55.4%) and 139 failures (17.0%). The failure group had lower gestational age, birth weight, and 1-minute and 5-minute Apgar scores compared to the successful group (P<0.05). The failure group also had a higher proportion of respiratory distress syndrome (RDS) diagnosed upon NICU admission, higher maximum positive end-expiratory pressure during NIV, and higher percentages of reaching the required maximum fraction of inspired oxygen (FiO2) ≥30%, ≥35%, and ≥40% throughout the initial NIV process compared to the successful group (P<0.05). Gestational age (OR=0.671, 95%CI: 0.581-0.772), RDS (OR=1.955, 95%CI: 1.181-3.366), and FiO2 ≥30% (OR=2.053, 95%CI: 1.106-4.044) were identified as risk factors for initial NIV failure in these infants with gestational age <32 weeks (P<0.05). The failure group had higher incidences of complications such as pulmonary infections, pneumothorax, retinopathy of prematurity, moderate to severe bronchopulmonary dysplasia, and severe intraventricular hemorrhage during hospitalization, as well as longer hospital stays and higher total costs compared to the successful group (P<0.05). CONCLUSIONS: Smaller gestational age, a diagnosis of RDS in the NICU, and achieving a maximum FiO2 ≥30% during the initial NIV process are risk factors for initial NIV failure in infants with gestational age <32 weeks. Initial NIV failure significantly increases the risk of adverse outcomes in this population.

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Randomized controlled trials have reported psychoanalytic psychotherapy to improve longer-term post-treatment outcomes in patients with treatment-resistant depression. In this case study, we examine the therapy process of a female trial participant diagnosed with treatment-resistant depression. Structured clinical assessments indicated that the patient's level of depression remained unchanged during and after treatment. Over the course of the therapy, she repeatedly broke away from important others and finally also from the therapy itself, which we linked to the impact of earlier experiences of abandonment on her internal world. In the discussion, we present a variety of reflections that were put forward by the authors during a series of case discussion meetings. Some of these reflections relate to how the inner world of this patient might have triggered a negative therapeutic reaction and a destructive pattern of repetition. The interpretative stance, in which the therapist interpreted this reaction as indicative of a psychic conflict and linked this conflict to the therapeutic relationship, seemed to be experienced by the patient as unhelpful and persecutory. Other elements that were brought up include basic distrust, lack of symbolization and trauma in the patient, as well as the constraints of the research context.

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BACKGROUND: Vascular access intervention therapy (VAIVT) is widely used as a treatment for arteriovenous fistula (AVF) failure. However, recurrent AVF failure is a major concern for dialysis patients. By prospectively observing patients after an initial VAIVT, we attempted to identify risk factors for developing restenosis of AVF. METHODS: This single-center prospective study evaluated 57 patients who underwent their first VAIVT procedure at our hospital from April 2022 through March 2023. We performed blood and biochemical tests during the first VAIVT to collect data on clinical variables. Ultrasonography was used to measure vessel diameter reduction rate, flow volume (FV) reduction rate, and increase in resistance index (RI) rate over a 3-month period. RESULTS: Within 3 months, 24 patients developed short-term shunt stenosis and 30 did not. Three were not traceable. In a comparison of the two groups, significant differences were observed in albumin (ALB), FV, RI, and elbow shunt. Analysis of change rates in the three ultrasound findings identified five factors (hematocrit, platelet count, activated partial thromboplastin time, ALB, and FV). The results of logistic regression models revealed that ALB was the most significant predictive factor for short-term shunt stenosis (p = 0.031). CONCLUSION: In conclusion, our findings suggest that low serum ALB at the time of initial VAIVT is a significant risk factor for short-term recurrence of AVF failure in hemodialysis patients. These findings emphasize the importance of careful routine monitoring to reduce the risk of AVF failure and associated complications.

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BACKGROUND: Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. METHODS: This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. RESULTS: A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW. CONCLUSION: This pilot trial preliminarily confirmed that nebulized inhalation of PAW can alleviate pneumonia in moderate COVID-19 patients with antiviral treatment failure, with no adverse reactions observed. This still needs to be verified by large-scale studies. TRIAL REGISTRATION: Chinese Clinical Trial Registry; No.: ChiCTR2300078706 (retrospectively registered, 12/15/2023); URL: www.chictr.org.cn .

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INTRODUCTION: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate response to NSAIDs, biological disease-modifying antirheumatic drugs (bDMARDs) should be introduced according to the recommendations of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. Until 2015, only bDMARD was recommended for axSpA in case of failure to anti-tumour necrosis factor (TNF). The 2022 Assessment of SpondyloArthritis International Society (ASAS)-EULAR recommendation proposed to start an alternative bDMARD but without advocating a switch in mode of action as proposed in rheumatoid arthritis. Since 2015, the inhibition of interleukin (IL)-17 has demonstrated efficacy in axSpA. Then, we designed a randomised multicentre clinical trial to identify the more effective treatment after a first anti-TNF failure in axSpA, comparing an anti-IL-17 to a second anti-TNF. METHODS AND ANALYSIS: The ROC-SpA (Rotation Or Change of biotherapy after first anti-TNF treatment failure in axSpA patients) study is a prospective, randomised, multicentre, superiority open-label phase IV trial comparing an anti-IL-17 strategy (secukinumab or ixekizumab) to a second TNF blocker in a 1:1 ratio. Patients with an active axSpA (Bath Ankylosing Spondylitis Disease Activity Index >4 or ankylosing spondylitis disease activity score (ASDAS) >3.5) with inadequate 3 months response to a first anti-TNF and with a stable dose of conventional synthetic DMARDs, oral corticosteroids and/or NSAIDs for at least 1 month are included in 31 hospital centres in France and Monaco. The primary outcome is the ASAS40 response at week 24. The secondary outcomes are ASAS40 at weeks 12 and 52, other clinical scores (ASAS20, partial remission rate, ASDAS major improvement rate) at weeks 12, 24 and 52 with the drugs and anti-drugs concentrations at baseline, weeks 12, 24 and 52. The primary analysis is performed at the end of the study according to the intent-to-treat principle. ETHICS AND DISSEMINATION: Ethics approval was obtained from the committee for the protection of persons (Comité de protection des personnes Ouest IV #12/18_1, 6 February 2018) and registered in ClinicalTrials.gov and in EudraCT. Results of this study, whether positive or negative, will be presented at national and international congresses, to national axSpA patient associations and published in a peer-reviewed journal. It could also impact the international recommendation to manage patients with axSpA. TRIAL REGISTRATION NUMBER: NCT03445845 and EudraCT2017-004700-22.

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OBJECTIVE: To evaluate the surgical outcomes and predictors of failure of Single Incision Mini Sling (Ophira) in women with urodynamic stress incontinence. MATERIALS AND METHODS: Records of 115 women underwent anti-incontinence procedure using Ophira Mini Sling from June 2019 to September 2020 reviewed. Subjective evaluation was assessed using validated IIQ-7, UDI-6, POPDI-6 and PISQ-12 questionnaires. Multichannel urodynamics, 1-h pad test and 72-h voiding diary was performed as objective evaluation. Primary outcome was the objective cure rate of negative urine leak on provocative filling cystometry and 1-h pad test weight <2 g, and subjective cure rate was negative response to question 3 of UDI-6. Secondary outcome was to identify risk factors associated with failure for Ophira. RESULTS: Total of 108 women were evaluated. The objective cure rate was 91.7% with subjective cure rate of 86.1%. Comparison of clinical outcome shows significant improvement of USI post-operatively (p < 0.001) and reflected in 1-h pad test (p < 0.001). Improvement in all subjective evaluation parameters is seen except for POPDI-6. Failure of Ophira correlate significantly in women age >66 years, presence of asthma, pre-operative Intrinsic Sphincter Deficiency (ISD), and Maximum Urethral Closure Pressure (MUCP) value < 40 cmH20. CONCLUSION: Ophira Single Incision Mini Sling is safe and effective treatment option for USI, showing high objective and subjective cure rates with low incidence of complications. Non-modifiable risks of age ≥66 years, asthma status, pre-operative intrinsic sphincteric deficiency and low maximal urethral closure pressure were the factors of failure for Ophira.

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OBJECTIVE: Low Maximal Urethral Closure Pressure (MUCP) is linked to unfavourable outcome of anti-incontinence surgery, however the cut-off value varied within studies. This study aimed to predict the cut-off value of MUCP that contributes to poor outcome of Mid-Urethral Sling (MUS) surgery in Urinary Stress Incontinence (USI) patients. MATERIALS AND METHODS: Records of 729 women underwent MUS procedure from January 2004 to April 2017 reviewed. Patients were divided into four MUCP groups, which were <20 cmH2O (≥20 and < 40) cmH2O (≥40 and ≤ 60) cmH2O and >60 cmH2O. Objective evaluation comprising 72-h voiding diary, multichannel urodynamic study (UDS) and post-operative bladder neck angle measurement. Subjective evaluation through validated urinary symptoms questionnaires. Primary outcome was objective cure rate of negative urine leak on provocative filling cystometry and 1-h pad test weight <2 g, and subjective cure rate was negative response to question 3 of UDI-6. Secondary outcome was identifying risk factors of cure failure for MUS in low MUCP groups. To identify the risk factors of cure failure, MUCP groups were narrowed down into <40 cmH2O or ≥40 cmH2O. RESULTS: Total of 688 women evaluated. Overall objective cure rate was 88.2% with subjective cure rate of 85.9%. Objective and subjective cure rates were lower in groups with low MUCP <40 cmH2O. Failure of MUS correlate significantly in patients with low MUCP <40 cmH20, bladder neck angle <30° and Functional urethral length (FUL) < 2 cm. CONCLUSION: Women with MUCP <40cmH2O, bladder neck angle <30° and FUL < 2 cm are more likely to have unfavorable outcome following MUS surgery. We proposed the cut-off low MUCP <40cmH2O as predictor for fail MUS surgery in SUI patients.

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BACKGROUND: The positioning error of femoral tunnel was the key factor leading to the failure of anterior cruciate ligament (ACL) reconstruction. This study aimed to propose a new femoral tunnel classification to guide revision ACL reconstruction. METHODS: Totals of 150 patients with ACL reconstruction failure from 2017 to 2023 were enrolled in this retrospective study. According to the tunnel diameter, shape, posterior wall and the positioning relationship with the Lateral Intercondylar Ridge on the three-dimensional CT imaging, we divided the femoral tunnels into four types: Type I off-target type, Type II straddled type, Type III anatomical type, and Type IV irregular type. Finally, explored the inter-observer reliability within two groups of doctors (Group A, 12 high seniorities; Group B, 12 low seniorities), and evaluated the intra-observer reliability within 6 doctors after two months. Clinical evaluation was performed using the Lysholm score, Tenger activity score, Pivot Shift and anterior knee laxity measurements. RESULTS: Among 150 cases of femoral tunnel three-dimensional CT reconstructed imaging, 144 cases were successfully included in the classification system, and 6 cases were confirmed as uncertain type. We measured the Kappa (κ) coefficient of group A was significantly higher than that of group B (κ 0.72 VS 0.68), and the κ coefficient of group A was still higher than group B (κ 0.69 VS 0.62) after further dividing Type III anatomical type into three subtypes. In addition, the κ coefficients of intra-observer reliability were all exceeded 0.73. Clinical follow-up showed that 9 patients had good knee joint motor function and stability after operation. CONCLUSION: The new femoral tunnel classification was reliable and had clinical guiding significance based on three-dimensional CT imaging. LEVEL OF EVIDENCE: Level III.

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BACKGROUND: Sexual and gender minorities (SGMs) are at higher risk of HIV incidence compared to their heterosexual cisgender counterparts. Despite the high HIV disease burden among SGMs, there was limited data on whether they are at higher risk of virologic failure, which may lead to potential disease progression and increased transmission risk. The All of Us (AoU) Research Program, a national community-engaged program aiming to improve health and facilitate health equity in the United States by partnering with one million participants, provides a promising resource for identifying a diverse and large volunteer TGD cohort. Leveraging various data sources available through AoU, the current study aims to explore the association between sexual orientation and gender identity (SOGI) and longitudinal virologic failure among adult people with HIV (PWH) in the US. METHODS: This retrospective cohort study used integrated electronic health records (EHR) and self-reported survey data from the All of Us (AoU) controlled tier data, version 7, which includes participants enrolled in the AoU research program from May 31, 2017, to July 1, 2022. Based on participants' sexual orientation, gender identity, and sex assigned at birth, their SOGI were categorized into six groups, including cisgender heterosexual women, cisgender heterosexual men, cisgender sexual minority women, cisgender sexual minority men, gender minority people assigned female at birth of any sexual orientation, and gender minority people assigned male at birth of any sexual orientation. Yearly virologic failure was defined yearly after one's first viral load testing, and individuals with at least one viral load test > 50 copies/mL during a year were defined as having virologic failure at that year. Generalized linear mixed-effects models were used to explore the association between SOGI and longitudinal virologic failure while adjusting for potential confounders, including age, race, ethnicity, education attainment, income, and insurance type. RESULTS: A total of 1,546 eligible PWH were extracted from the AoU database, among whom 1,196 (77.36%) had at least one viral failure and 773 (50.00%) belonged to SGMs. Compared to cisgender heterosexual women, cisgender sexual minority women (adjusted Odds Ratio [aOR] = 1.85, 95% CI: 1.05-3.27) were at higher risk of HIV virologic failure. Additionally, PWH who were Black vs. White (aOR = 2.15, 95% CI: 1.52-3.04) and whose insurance type was Medicaid vs. Private insurance (aOR = 2.07, 95% CI: 1.33-3.21) were more likely to experience virologic failure. CONCLUSIONS: Maintaining frequent viral load monitoring among sexual minority women with HIV is warranted because it allows early detection of virologic failure, which could provide opportunities for interventions to strengthen treatment adherence and prevent HIV transmission. To understand the specific needs of subgroups of SGMs, future research needs to examine the mechanisms for SOGI-based disparities in virologic failure and the combined effects of multi-level psychosocial and health behavior characteristics.

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Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.

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