Long-term Follow-up Visits Research Articles

Case report: Novel deletions in the 6p21.33 involving the CSNK2B gene in patients with Poirier-Bienvenu neurodevelopmental syndrome and literature review

BackgroundSeizures have been identified in most patients with CSNK2B-related Poirer-Bienvenu Neurodevelopment syndrome (POBINDS). Detailed descriptions of seizure phenotypes, various genotypes, and long-term follow-up visits are required for clinicians to provide reasonable clinical management for such patients.Case summaryWe report two new Chinese patients with varying sizes of 6p21.33 deletions encompassing the CSNK2B gene who presented with intellectual disability and seizures. Furthermore, we conducted a literature review of previously reported patients with 6p21.33 deletions or CSNK2B variants. We summarized and analyzed the clinical characteristics of these patients with seizures. The occurrence of a biphasic pattern of epilepsy and pharmacoresistant epilepsy in patients with CSNK2B variants is severely underestimated. One of our patients underwent a long follow-up period and presented with comprehensive disease progression.ConclusionOur data suggest that the CSNK2B variant or 6p21.33 deletion should be considered in patients with intellectual disability and epilepsy, especially those characterized by biphasic patterns and digital anomalies.

Clinical and radiological assessment of the Polish modification of the Ilizarov external fixator for the treatment of intra-articular calcaneal fractures.

There is currently no established gold standard for the treatment of calcaneal fractures. To conduct a clinical and radiological evaluation of patients following intra-articular calcaneal fractures treated with the Polish modification of the Ilizarov method. This was a 2-center retrospective study. We evaluated 27 patients (2 women and 25 men) aged 28-73 years (mean age 50.5 years) after treatment of intra-articular calcaneal fractures with the Polish modification of the Ilizarov method. We assessed pain using a visual analogue scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) scores, patient satisfaction with treatment, use of analgesics, duration of Ilizarov treatment, length of hospital stay, duration of surgery, patient's declared willingness to choose the same treatment again, complications, degenerative changes, Böhler angle, inflection angle, and Gissane angle. The mean follow-up period was 3 years and 2 months. Following treatment, the mean VAS pain score was 2.3. Prior to surgery, all patients were taking analgesics in comparison with only 2 patients (7.4%) at long-term follow-up. The treatment was rated as satisfactory by 11 patients, with 16 patients rating it as highly satisfactory. The mean post-treatment AOFAS score was 76.6 points. The Ilizarov fixator was removed after a mean period of 88 days. The mean duration of hospital stay was 7.4 days. The mean duration of the procedure was 44 min. All patients would choose the same treatment again. Complications were observed in 5 patients. The long-term follow-up visit revealed degenerative changes in the talocalcaneal joint in 8 patients. The median Böhler angle was 5.5° preoperatively and 28.5° postoperatively, p < 0.001. The median preoperative inflection angle of 160° decreased to 145°, p < 0.001. The median preoperative Gissane's angle of 119° increased significantly to a median postoperative value of 143°, p < 0.001. The patients achieved good clinical and radiological outcomes.

Chronic Refractory Cough: Long-Term Outcomes Following Cough Suppression Therapy

ObjectiveThis study aimed to determine the long-term outcomes of patients with chronic refractory cough (CRC) following treatment for cough suppression therapy (CST). Currently, there is a lack of objective data regarding the long-term outcome of behavioral treatment for CRC. MethodsFrom the charts of 106 adult patients diagnosed with CRC, 24 patients were identified as having long-term data at least 3 months post-CST in the form of otolaryngologic examination, Voice Handicap Index-10 (VHI-10), and Cough Severity Index (CSI) scores. Patients underwent otolaryngologic evaluation and completed the VHI-10 and CSI assessments during pretreatment, posttreatment, and long-term follow-up visits. Patients were also divided into two groups based on their number of comorbidities. ResultsTwenty of the 24 patients had significant reduction in cough severity after completing CST (P < 0.001). A significant difference was also found in CSI scores from pretherapy to the long-term follow-up visits (P = 0.001). No significant difference was found in CSI scores from posttherapy to long-term follow-up visits (P = 0.93). No significant difference was found in VHI-10 scores over time (P = 0.83). No correlation was found between changes in cough and voice severity and number of comorbidities at the tested level. ConclusionsFindings of no significant change in CRC over the long term compared to posttherapy measures suggest that patients were able to maintain improvement in cough over the long term despite various comorbidities. The current results suggest that CST represents a satisfactory approach to treating CRC and provides patients with an ongoing tool to maintain reduced cough severity. No significant correlations between number of comorbidities and mean CSI or VHI-10 scores were found over the long term.

Special considerations in paediatric dental trauma.

Traumatic dental injuries (TDIs) in the paediatric population are common and frequently seen in general dental practice. The management of TDIs can be challenging and, in most cases, the General Dental Practitioner is tasked with the initial assessment and emergency treatment. Patients and their families typically attend with elevated levels of distress, which is complicated by the limited dental experience of some children. Behaviour management is essential and helps prepare patients for dental care at both their emergency and follow-up appointments. Early and accurate diagnosis in combination with appropriate treatment contributes to favourable outcomes for traumatised teeth. Early discussions with or referral to paediatric dental teams for management of complex TDIs is encouraged, however shared follow-up care is beneficial over the long-term. In specific cases, initial dental treatment can be delayed by a few days to a subsequent appointment, allowing the dental team to book sufficient time for the treatment and for the patient and their families to prepare. Education of the patients and adults with parental responsibility is essential to manage expectations, explain likely complications and encourage attendance for long-term follow-up visits. This paper discusses the management of paediatric patients to aid the primary care practitioner in providing effective immediate and long-term care.

Variability of somatosensory evoked potential and motor evoked potential change criteria in thoracic spinal decompression surgery based on preoperative motor status

Background contextCombined somatosensory- and motor-evoked potential (SSEP and MEP) changes for predicting prognosis in thoracic spinal surgery have been variably reported. PurposeWe aimed to explore the validity of combined SSEP and MEP for predicting postoperative motor deficits (PMDs) in thoracic spinal decompression surgery (TSDS) and identify a relatively optimal neurophysiological predictor of PMDs in patients based on preoperative motor status. Study settingRetrospective study. Patient sampleA total of 475 patients were analyzed. Outcome MeasuresA reduction in muscle strength by more than or equal to one manual muscle testing (MMT) grade postoperatively compared with the preoperative MMT grade was identified as PMDs. Postoperative motor deficits were detected by comparing the preoperative and postoperative physical examination findings in short- and long-term follow-up visits. MethodsAll patients were divided into two subgroups according to preoperative motor status. The following data were collected: (1) demographic data; (2) IONM (intraoperative neuromonitoring) data; and (3) postoperative motor outcomes. Binary logistic regression analysis was performed to assess the efficacy of IONM change to predict PMDs. A receiver operating characteristic curve (ROC) was used to establish optimal IONM warning criteria. ResultsNinety-eight patients had severe preoperative motor deficits (Group S), and 377 patients did not (Group N). MEP and SSEP change was effective for predicting PMDs in the short term (p<.01) and long term (p<.01) for TSDS patients. In Group N, the cutoff values for predicting PMDs in the short term were a decrease of 65% in SSEP amplitude and 89.5% in MEP amplitude of the baseline value. Furthermore, the cutoff values for predicting PMDs in the short term were durations of change of 24.5 minutes for SSEP and 32.5 minutes for MEP. In Group S, however, the cutoff values for predicting PMDs in the short term were a decrease of 36.5% in SSEP amplitude and 59.5% in MEP amplitude of the baseline value. Moreover, the critical values for predicting short-term PMDs were durations of change of 16.5 minutes for SSEP and 17.5 minutes for MEP. ConclusionsThe optimal IONM changes for prediction vary depending on preoperative motor status. Combined SSEP and MEP are excellent for predicting PMDs in TSDS.

INCIDENCE ON COST AND DURATION OF THERAPY OF POSSIBLE POSTOPERATIVE WOUND INFECTIONS FROM TRAUMA WITH PROSTHETIC DEVICES, PREVENTIVELY TREATED AND UNTREATED, USING ANTIBACTERIAL GELS AT P.O. SAN GIULIANO, ASL NAPLES 2 NORTH

Introduction: Bacterial infections associated with implanted biomaterials represent the most significant complication in orthopedics, and they constitute the primary reason for the failure of primary hip and knee prostheses.The prevention of infections associated with implanted biomaterials should simultaneously focus on at least two objectives: inhibition of biofilm formation and minimization of suppression of the local immune response.Some of the technologies proposed for this purpose in clinical practice have already shown strong evidence of antibacterial effectiveness, safety, and resistance. The time is ripe for further development and experimentation of these technologies in a clinical context. Material and Methods: The study was conducted by observing wounds within 6 months following the treatments, and the purpose of the work was to evaluate the cost and benefit aspects in patients treated with defensive antibacterial gels during orthopedic prosthetic and/or synthesis surgeries at the P.O. San Giuliano ASL Napoli 2 Nord. The aim was to assess the effectiveness of the treatment applied to patients who underwent orthopedic prosthetic and/or synthesis surgeries. The wound conditions of treated patients and untreated patients were compared at 6 months after orthopedic surgery. Simultaneously, the costs incurred by the National Health Service (SSN) and the related benefits obtained for the treated patients and untreated patients were also analyzed. This observational and retrospective study was conducted over 6 months on a cohort of 60 patients from the orthopedic department and outpatient clinic of P.O. San Giuliano ASL Napoli 2, who underwent post-traumatic interventions. The cohort was divided into two groups: Group A (gA) included 30 operated patients whose wounds and/or devices used were treated with gels designed for decontamination, aiming to prevent infections; Group B (gB) consisted of 30 operated patients who were not treated with any such device. The study involved a 6-month observation of both groups, evaluating the possible onset of infections, their duration (until complete healing, including potential complications), and the average cost of the necessary treatment (monitoring the use of drugs, medical supplies, and devices).A value scale was established based on the average cost incurred and the average treatment duration for each of the 4 levels on the scale. Results: At the end of the study period, 30 patients from the cohort were observed in group gA, and 30 in group gB.Within group gA, 2 patients experienced infections that positioned them in the first two levels of the scale, while in group gB, 8 patients required treatment for infections that placed them at different levels of the scale based on the treatment received and its associated cost. The economic impact is significant and variable, depending on the extent of usage indications (e.g., applying the device alone or as a carrier in combination with antibiotics in all subjects undergoing primary and revision arthroplasty surgeries, or fracture osteosynthesis, or only in a subset of them, e.g., patients selected at risk of infections, subjects undergoing prosthesis reimplantation, osteosynthesis of open traumatic fractures, etc.). Conclusions:The management of an infection that develops after orthopedic prosthetic and/or synthesis surgery leads the patient to seek and rely on long-term medical follow-up visits and specialized nursing assistance. The total costs for the care of the 10 infected patients show that the overall expenditure related to the 8 patients in group gB is much higher than that of the total 2 patients in group gA, both because of the fivefold difference in terms of number, which demonstrates how treatment with antibacterial gel reduces the incidence of infections, and also because the infections that occurred in the case of the 2 patients in group gA are milder and more manageable. Also considering the costs related to the use of antibacterial gel on wounds and/or prosthetic/osteosynthesis devices, the economic savings are still significant considering the cost of pharmacological treatments for infections and those for their potential complications.

Dogs with congenital extrahepatic portosystemic shunts that have persistent shunting after surgery have a higher prevalence of urolithiasis.

To report the presence of urolithiasis in dogs long-term after gradual attenuation of congenital extrahepatic portosystemic shunts (cEHPSS). 25 client-owned dogs that underwent gradual attenuation of a cEHPSS, of which 19 had a closed cEHPSS and 6 developed multiple acquired portosystemic shunts (MAPSS) following surgery. A retrospective study with prospective follow-up was performed. Dogs that underwent cEHPSS surgery and had their postoperative cEHPSS status determined by transsplenic portal scintigraphy or CT angiography 3 months postoperatively were prospectively contacted and invited for a long-term follow-up visit (a minimum of 6 months postoperatively). Retrospective data were collected, and during the prospective follow-up visit a thorough history, blood tests and urinalysis, and ultrasonography of the urinary tract were performed to assess the presence of urinary signs and urolithiasis. Of 25 included dogs, 1 of 19 (5%) dogs with closed cEHPSS and 4 of 6 (67%) dogs with MAPSS had urolithiasis at long-term follow-up. Three (50%) dogs with MAPSS developed new uroliths. Long-term, dogs with closed cEHPSS that initially presented with and without urolithiasis had significantly less urolithiasis compared to dogs with MAPSS (P = .013 and P = .010, respectively). In the 4 dogs with closed cEHPSS that initially presented with nephrolithiasis, nephroliths became smaller or were no longer visible at the long-term follow-up visit. Dogs that developed MAPSS following cEHPSS surgery are at greater risk of urolithiasis compared to those with closed cEHPSS. Furthermore, ammonium urate uroliths might dissolve if portosystemic shunting ceases to exist.

Surveillance after childhood cancer: are survivors with an increased risk for cardiomyopathy regularly followed-up?

We aimed to study adherence to cardiac screening in long-term childhood cancer survivors (CCS) at high risk of cardiomyopathy. This study involved 976 5-year CCS at high risk for cardiomyopathy from the French Childhood Cancer Survivor Study. Determinants of adherence to recommended surveillance were studied using multivariable logistic regression models. Association of attendance to a long-term follow-up (LTFU) visit with completion of an echocardiogram was estimated using a Cox regression model. Among participants, 32% had an echocardiogram within the 5 previous years. Males (adjusted RR [aRR] 0.71, 95% CI 0.58-0.86), survivors aged 36-49 (aRR 0.79, 95% CI 0.64-0.98), Neuroblastoma (aRR 0.53, 95% CI 0.30-0.91) and CNS tumour survivors (aRR 0.43, 95% CI 0.21-0.89) were less likely to adhere to recommended surveillance. Attendance to an LTFU visit was associated with completion of an echocardiogram in patients who were not previously adherent to recommendations (HR 8.20, 95% CI 5.64-11.93). The majority of long-term survivors at high risk of cardiomyopathy did not adhere to the recommended surveillance. Attendance to an LTFU visit greatly enhanced the completion of echocardiograms, but further interventions need to be developed to reach more survivors.

Predictive factors of long-term follow-up attendance in very long-term childhood cancer survivors.

Long-term follow-up (LTFU) clinics have been developed but only some childhood cancer survivors (CCS) attend long-term follow-up (LTFU). To identify factors that influence LTFU attendance. Five-year CCS treated for a solid tumor or lymphoma in Gustave Roussy before 2000, included in the FCCSS cohort (French Childhood Cancer Survivor Study), aged >18years and alive at the date of the LTFU Clinic opening (January 2012) were invited to a LTFU visit. Factors associated with attendance at the LTFU clinic between 2012 and 2020 were estimated using logistic regression analyses. Analyses included different types of factors: clinical (tumor characteristics, cancer treatments, late effects), medical (medical expenses were used as a proxy of survivor's health status), social (deprivation index based on census-tract data relating to income, educational level, proportion of blue-collar workers, and unemployed people living in the area of residence), and spatial (distance to the LTFU clinic). Among 2341 CCS contacted (55% males, mean age at study,45years; SD±10years; mean age at diagnosis,6years; SD±5years), 779 (33%) attended at least one LTFU visit. Initial cancer-related factors associated with LTFU visit attendance were: treatment with both radiotherapy and chemotherapy (odds ratio [OR],4.02; 95% CI,2.11-7.70), bone sarcoma (OR,2.43; 95% CI,1.56-3.78), central nervous system primitive tumor (OR,1.65; 95% CI,1.02-2.67), and autologous hematopoietic cell transplant (OR,2.07; 95% CI,1.34-3.20). Late effects (OR,1.70; 95% CI,1.31-2.20), highest medical expenses (OR,1.65; 95% CI,1.22-2.22), living in the most advantaged area (OR vs. the most deprived area=1.60; 95% CI,1.15-2.22), and shorter distance from LTFU care center (<12miles) also increased attendance. Patients who are apparently healthy as well as socially disadvantaged and living far away from the center are less likely to attend LTFU care. Among 2341 adult childhood cancer survivors contacted between 2012 and 2020, 33% attended at least one long-term follow-up visit. Clinical factors related to attendance were multimodal treatment of first cancer (combining chemotherapy and radiotherapy), stem cell transplant, type of diagnosis (bone tumor and central nervous system primitive tumor), late effects (at least one disease among second malignancy, heart disease, or stroke), and highest medical expenses. In addition, the study identified social and spatial inequalities related to attendance, with independent negative effects of distance and social deprivation on attendance, even though the medical costs related to the long-term follow-up examinations are covered by the French social security system.

Complications and Outcome of Cranial Cruciate Ligament Disease in Small Dogs Treated with Tiny TTA Rapid

AbstractThe aim of this study was to evaluate the complications and the long-term outcome of TTA Tiny in small dogs using data from pressure-sensitive walkway analysis and the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire. This is a retrospective study. Dogs under 15 kg were included. Breed, weight, gender, age, and lameness were recorded. Clinical examination, radiographs, and pressure-sensitive walkway analysis were performed during the long-term follow-up visit. Radiographs were assessed for the postoperative patellar tendon angle (PTA), bone healing, and implant position, and the postoperative complications were recorded. Twenty-nine stifles were included. One dog (3%) had an intraoperative major complication and 14 (48%) had minor complications. Medium- to long-term follow-up was available in 20 of the 23 dogs (87%). Eight (40%) dogs were followed up by telephone using the LOAD questionnaire and 12 dogs (60%) came back for a long-term follow-up appointment. The average LOAD score was 3.6 and the average lameness score was 0. All the dogs presented at a clinical follow-up were considered lame free. All the owners were pleased with the long-term result after surgery based on the LOAD score and the return to normal activity. The result from this study showed low rate of perioperative complications with the use of the TTA Tiny implant in small dogs and a good long-term outcome based on client questionnaire and the result from pressure-sensitive walkway analysis.

Intravitreal injections with anti-VEGF agent aflibercept versus subthreshold micropulse laser for chronic central serous chorioretinopathy: the alternative treatment regimens for verteporfin-shortage in China

Purpose To compare short-term anatomical outcomes observed in optical coherence tomography (OCT) between intravitreal injection (IVI) with anti-vascular endothelial growth factor (VEGF) agent aflibercept (IVA) and subthreshold micropulse laser (SML) therapy in chronic central serous chorioretinopathy (cCSC). Methods Thirty-nine eyes of 36 patients with symptomatic cCSC in this retrospective study received either IVA or SML between December 2020 and August 2022. Spectral-domain-OCT (SD-OCT) findings were compared between the two treatment groups in terms of central macular thickness (CMT), serous subretinal fluid (SRF) height, the presence of pigment epithelial detachment (PED) and subretinal hyperreflective foci (HF) at baseline and one-month follow-up visits. Results Both groups showed significant reductions in CMT and SRF at one-month follow-up visit. However, there were no statistically significant differences between the IVA and SML groups. Complete SRF resolution was observed in 10 out of 21 and 7 out of 18 eyes in the IVA and SML groups, respectively; however, retinal pigment epithelial (RPE) damage remained persistent in patients with PEDs at baseline. Conclusions Both IVA and SML were effective in treating cCSC. IVA and SML treatments had comparable effects in reducing CMT and SRF in eyes with cCSC. Further prospective studies with larger sample sizes and long-term follow-up visits are warranted to identify the long-term efficacy.

Patient perspectives on post-bariatric surgery nutritional supplementation.

Bariatric procedures increase patient risk of long-term metabolic complications primarily due to nutrient deficiencies. The mainstay of prevention includes routine vitamin and mineral supplementation; however, patient-reported barriers to daily compliance are poorly understood. Post-bariatric surgery patients electively participated in an 11-point outpatient survey at a single academic institution. Surgical procedures included either laparoscopic sleeve gastrectomy (SG) or gastric bypass (GB). At the time of survey, patients ranged from 1-month to 15years from surgery. Survey items consisted of dichotomous (yes/no), multiple choice, and open-ended free response questions. Descriptive statistics were evaluated. Two hundred and fourteen responses were collected, 116 (54%) underwent SG and 98 (46%) underwent GB. Of these, 49% of samples were during short-term postoperative follow-up visits (0-3months), 34% intermediate follow-up (4-12months), and 17% long-term follow-up (> 1year). A total of 98% of patients reported that insurance did not cover their supplement cost. Most patients reported current vitamin use (95%), with 87% reporting daily compliance. Daily compliance was observed in 94%, 79%, and 73% of SG patients at short-, intermediate-, and long-term follow-up visits, respectively. While GB patients reported daily compliance in 84%, 100%, and 92% of short, intermediate, and long-term responses. Of those who were unable to take vitamins daily, non-compliance was attributed most to forgetting (54%), and less often to side effects (11%), or taste (11%). Patient-reported strategies for remembering to take vitamins included tying into daily routine (55%), use of a pill box (7%), and alarm reminders (7%). Daily compliance with post-bariatric surgery vitamin supplementation does not appear to vary based on postoperative time-period or surgical procedure. While a minority of patients struggle with daily compliance, factors associated with non-compliance include patient forgetting, side effects, and taste. Widespread utilization of patient-reported daily reminder strategies may lead to improved overall compliance and reduce incidence of nutritional deficiencies.

288 Propranolol Use in Adult Burn Patients: Results from a Multi-center Safety and Efficacy Trial

Abstract Introduction The hypermetabolic response induced by a large burn is associated with increased cardiac work, total body wasting, and impaired physical function, leading to delays in psychosocial recovery and reintegration into society, and persistence of chronic conditions. Modulation of this response could reduce long-term burn morbidity. Catecholamines drive burn-induced hypermetabolism, therefore clinicians have employed the non-selective beta-adrenergic receptor blocker propranolol to reduce cardiac stress and the hypermetabolic response. Here, in a masked, placebo-controlled study, we investigated the safety and efficacy of the administration of propranolol to adult burn patients during the acute hospitalization period. Methods Adults with large burns (n=157, mean 38 ± 15% TBSA) were enrolled at 13 participating centers. Subjects were randomized to receive placebo (n=75) or propranolol (n=82) with data collected for 72 and 79 subjects, respectively. Propranolol administration was initiated with an oral dose of 0.2 mg/kg dose and adjusted to decrease mean heart rate by 20%. The primary endpoint was effect on cardiac rate pressure product (CRPP), while the secondary endpoints included infections and survival. Adverse events were also tracked. Assessments were conducted between the time of consent and discharge, with a long-term follow-up visit occurring approximately 5 months post-burn on average. Results CRPP was significantly reduced with propranolol during the acute hospitalization period (p&amp;lt; 0.0001, Fig 1). The initial dose of propranolol adequately reduced heart rate in most patients. Infections were not different between cohorts. Cardiac complications (atrial arrhythmias, ventricular arrhythmias, cardiac arrest) occurred at similar rates for each group, as did additional complications (abdominal compartment syndrome, deep vein thromboses, pneumothorax, pulmonary embolus). Mortality was similar for both the placebo and propranolol cohorts. Post-discharge heart rates and blood pressures were similar in both groups at approximately 5 months following injury. Conclusions This study demonstrates that the short-term administration of propranolol to adults with large burns decreases CRPP without increasing complications, infections, or mortality. Furthermore, a safe dosing strategy was identified. This strategy may be effective for reducing acute cardiac stress and hypermetabolism. Future studies should focus on the effects of propranolol administration for longer periods, determining the effects on additional endpoints like the hypermetabolic response, pathologic scarring, long-term cardiac dysfunction, whether smaller burns benefit from the administration of propranolol.

Association between outpatient follow-up and incidence of revision after knee and hip replacements: a population-based cohort study

BackgroundFollow-up visits 5 or 7 years after surgery were recommended for people having primary hip or knee replacement. The benefits of this practice to patients and the healthcare system, however, have not yet been specifically examined. The aim of this study was to investigate the association between long-term follow-up outpatient hospital visits and revision rates for patients who undergo primary knee or hip replacement surgery.MethodsCohorts were identified for patients undergoing knee or hip replacement surgery using medical records from primary care practices within the UK Clinical Practice Research Datalink (CPRD) GOLD dataset linked to hospital records from the English Hospital Episodes Statistics (HES) data. Two groups of patients were compared in terms of revision and mortality rates: those with at least one long-term (between five and 10 years since primary surgery) follow-up visit at the orthopaedic department (‘Follow-up’ group), and those without (‘No follow-up’ group).ResultsA total of 9856 (4349 in the Follow-up group) patients with knee replacement and 10,837 (4870 in the Follow-up group) with hip replacement were included in the analysis. For knee replacement, the incidence of revision was 3.6% for those followed-up and 0.6% for those not followed-up. An adjusted regression model confirmed the difference in the hazard ratio (HR) for revision was statistically significant (HR: 5.65 [95% CI 3.62 to 8.81]). Mortality at 4 years was lower for the Follow-up (17%) compared to the No follow-up group (21%), but this difference was not statistically significant (HR: 0.95 [0.84 to 1.07]). For hip replacement, the incidence of revision rates were 3.2 and 1.4% for the follow-up and not follow-up groups, respectively, the difference being statistically significant (HR: 2.34 [1.71 to 3.20]). Mortality was lower for the Follow-up (15%) compared to the No follow-up group (21%), but the difference was not statistically significant (HR: 0.91 [0.81 to 1.02]).ConclusionPatients attending follow-up orthopaedic consultations show a higher risk of revision surgery compared to those who are not followed-up. A cause for this difference could not be identified in this study but a likely explanation is that surgeons play an effective role as ultimate arbitrators when identifying patients to be included in long-term follow-up lists.

Trial in Progress: An Open-Label, Multi-Center, First in Human, Phase 1/2a Trial to Evaluate the Safety and Preliminary Efficacy of Autologous Tolerogenic Dendritic Cells Ex Vivo Loaded with Recombinant Factor VIII (FVIII) in Adults with Congenital Hemophilia a (HA) with Neutralizing Antibodies to FVIII and Having Failed Immune Tolerance Induction (ITI)

Background Severe hemophilia A is a congenital bleeding disorder caused by a lack of factor VIII (FVIII) in plasma. Without treatment patients experience prolonged bleeding, either spontaneously or following trauma, and even life-threatening bleeds. Replacement therapy with FVIII is the standard of care, but development of neutralizing antibodies to FVIII is common, which reduces or completely prohibits the effect of FVIII treatment. Idogen AB has developed a cell therapy platform with the main purpose of making patients tolerant to FVIII and thus eliminating the problem of the immune system producing neutralizing antibodies. The cell therapy product, ItolDC-028, is produced from autologous mononuclear cells, collected by leukapheresis. A GMP-facility at Radboud University Hospital in the Netherlands enriches and cultures cells into tolerogenic dendritic cells, finally loaded with FVIII-antigen and cryopreserved. By this unique process the autologous cells has undergone a specific culture process to induce tolerance to FVIII. Trial Design and Methods This trial is a first-in-human, phase 1/2a, open-label trial, evaluating the safety and preliminary efficacy with ascending single doses of autologous tolerogenic dendritic cells for the management of neutralizing antibodies against FVIII in patients with hemophilia A. Male subjects aged 18-60 years and diagnosed with severe hemophilia A, with neutralizing antibodies against FVIII, having failed immune tolerance induction (ITI) treatment or for whom it is not possible to treat with ITI, a reported peak titer of ≥ 5 Bethesda Units (BU) and ≥ 1 BU at inclusion are eligible for the trial. Concomitant emicizumab is allowed, but FEIBA and other FVIII-containing treatments are excluded except in the case of an urgent need to treat bleeding. The primary objective is safety/tolerability of ItolDC-028, evaluated as the number of adverse events (AEs), changes in vital signs, physical examination findings and laboratory assessments including titers of neutralizing antibodies (BU) and ECG recordings from administration of ItolDC-028 up to the week 26 visit. The secondary objective is to evaluate the preliminary therapeutic efficacy of three dose levels of ItolDC-028 through evaluation of immune response, titer of neutralizing antibodies (BU), FVIII recovery and half-life as response to FVIII challenge at the week 20 visit. A minimum of nine subjects will be included in a classic 3+3 trial design, with single incremental dose levels of 36x106, 72x106 and 144x106 cells. Three additional subjects can be included in each dose level, upon reported signs of dose-limiting toxicity. An Internal Monitoring Board will evaluate the safety of the first subject at each dose level to decide if the next subject can be treated, and then all subjects at each dose level prior to escalation to the next dose level. There will be at least 2 weeks between treatments within a dose level and at least 6 weeks between the dose levels. Figure 1. At each clinical site, frozen ItolDC-028 is thawed and given to the subject by an intravenous infusion. Subjects are followed for 26 weeks including physical examinations, vital signs, laboratory assessments, FVIII-antibody titers, immunological changes, bleeding episodes and quality-of-life questionnaires (EQ-5D and Haem-A-QoL). In addition, there will be a long-term follow-up visit after 52 weeks. Figure 2. Twenty weeks after ItolDC-028 administration, the subject will be challenged by an administration of FVIII (Kovaltry®, 50 IU/kg), to evaluate the preliminary efficacy of ItolDC-028. The trial will be performed in eight European academic hospitals. The first subject is planned to be enrolled in August 2022. The trial is approved by the Swedish and Norwegian Competent Authorities and by the Swedish Ethical Review Authority (July 2022) and will also be reviewed by EU and UK Authorities. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Functional, aesthetic, and sensory postoperative complications of female genital gender affirmation surgery: A prospective study

Female genital gender affirmation surgeries have increased in recent years. Prospective studies with homogeneous standardized techniques and outcomes assessment are scarce in the current literature. This study aims to: 1) report the functional, aesthetic, and sensory postoperative complications (POCs) of primary genital gender confirmation surgeries performed on transgender women and 2) compare functional and aesthetic POCs amongst three vaginoplasty techniques: inverted penile skin, penoscrotal skin graft, and pedicled intestinal flap vaginoplasty. All (n=84) consecutive transfemale individuals who underwent primary genital gender confirmation surgery from January 2015 to December 2016 at IMCLINIC were prospectively followed. Functional, aesthetic, and sensory POCs were registered according to the Clavien-Dindo POC classification. Functional POC rates after vaginoplasty at our centre were 19%, 12%, 13%, and 1% at short (one month), mid-early (three months), mid-late (six months), and long-term (one year) follow-up visits, respectively. None of them were severe complications (grades IV-V), 25% were grade III, and less than 20% were low-grade complications (grades I-II). Overall, aesthetic satisfaction was high (90%). The total number of secondary surgeries needed to satisfy the cosmetic outcome was 20 (aesthetic POC grade IIIb). No differences regarding functional or aesthetic complication rates amongst vaginoplasty techniques were encountered. Twelve months after surgery, 81% of patients had initiated sexual intercourse, and 96% reported clitoral sensitivity. In our experience, female genital gender affirmation surgery is a feasible, low-complication surgery that offers high satisfaction in the long term. Further multicentric well-designed research is mandatory to improve outcomes.

Long-term peripheral retinal vascular behavior in retinopathy of prematurity patients treated with ranibizumab intravitreal injection as monotherapy using fluorescein angiography

BackgroundFew challenges are faced with the introduction of anti-VEGF agents as a modality of treatment for retinopathy of prematurity. The clinical behavior and time course of regression post injection differ compared to post laser ablation. This study aims to evaluate the long-term peripheral retinal vascularization outcome of Ranibizumab intravitreal injections monotherapy in the treatment of retinopathy of prematurity.MethodHospital-based quasi-experimental study. Include ROP patients who received intravitreal ranibizumab (IVR), as primary treatment for type 1 ROP. Patients were examined under general anaesthesia to ensure documentation of all junctions of vascular and avascular zones. Images were taken by RetCam III, Phoenix ICON and fluorescein angiography was performed to describe vascular behaviors.ResultsThe mean gestational age was 24.67 weeks and the mean postmenstrual age at the time of intravitreal ranibizumab treatment was 36.3 weeks. Fluorescein angiography was performed at 155–288 weeks; most eyes showed two disk diameters of avascular peripheral retina. Only eyes with original aggressive ROP who required a second injection (six eyes) showed extensive peripheral avascular retina reaching zone I (13.64%). Neovascularization was evident in five eyes (11.36%), all with an original aggressive ROP and received multiple injections.ConclusionsRanibizumab treated babies with incomplete retinal vascularization require close and long-term follow-up visits to assess post injection vascular behavior. Peripheral retinal avascular zone of more than two-disc diameters was present in most of the patients evidenced by fluorescein angiography. Babies with initial diagnosis of aggressive ROP are more likely to have persistent peripheral neovascularization.

Endometrial Cryoablation for the Treatment of Heavy Menstrual Bleeding: 36-Month Outcomes from the CLARITY Study.

Study ObjectiveTo examine long-term outcomes from the pivotal study that evaluated the safety and effectiveness of the Cerene® Cryotherapy Device (Channel Medsystems, Berkeley, CA) in premenopausal women with heavy menstrual bleeding due to benign causes who have completed childbearing.MethodsThe prospective, multicenter, single-arm, open-label study had eight sites in the USA, one in Mexico, and two in Canada. Inclusion criteria included uterine sound ≤10 cm, endometrial cavity length 2.5 to 6.5 cm, age 25 to 50 years, a pictorial blood loss assessment chart score of ≥150, no submucosal myomata and/or uterine obstruction, distortion, or abnormality. A total of 242 subjects underwent a 2.5-minute cryoablation. Long-term follow-up visits were conducted at Month 24 and Month 36. Data collected included gynecological adverse events, description of last menstrual period, contraception status, self-report of pregnancy, medical or surgical interventions to treat abnormal uterine bleeding, satisfaction, recommendation, and quality of life (QoL). QoL outcomes were measured with the Menorrhagia Impact Questionnaire (MIQ) and the Premenstrual Symptoms Impact Survey (PMSIS™).Results201 subjects completed their Month 36 final study visit. Subject outcomes were comparable to those at Month 12. Eighty-nine percent of subjects reported amenorrhea, a lighter-than-normal, or normal period, 91% of subjects had no or slight limitations in MIQ measured activities, and 85% reported premenstrual symptoms at a low frequency. Eighty-five percent of the subjects were satisfied or very satisfied. The cumulative incidence of hysterectomy was 5% and reintervention was 8.7%. Forty-nine gynecologic adverse events (AE) were reported; one non-serious AE, postcoital bleeding, was reported as related to the procedure. No serious device-related or procedure-related AEs were reported.ConclusionStudy data demonstrate that the positive effects of Cerene Cryotherapy Device treatment are sustained through Month 36 and that the risks associated with the device and procedure are low (ClinicalTrials.gov; NCT02842736).

Long-term outcome of a pragmatic trial of multifaceted intervention (STROKE-CARD care) to reduce cardiovascular risk and improve quality-of-life after ischaemic stroke and transient ischaemic attack: study protocol

BackgroundPatients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of incident cardiovascular events and recurrent stroke. Despite compelling evidence about the efficacy of secondary prevention, a substantial gap exists between risk factor management in real life and that recommended by international guidelines. We conducted the STROKE-CARD trial (NCT02156778), a multifaceted pragmatic disease management program between 2014 and 2018 with follow-up until 2019. This program successfully reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA within 12 months after the index event. To investigate potential long-term effects of STROKE-CARD care compared to standard care, an extension of follow-up is warranted.MethodsWe aim to include all patients from the STROKE-CARD trial (n = 2149) for long-term follow-up between 2019 and 2021 with the study visit scheduled 3–6 years after the stroke/TIA event. The co-primary endpoint is the composite of major recurrent cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and vascular death) from hospital discharge until the long-term follow-up visit and health-related quality of life measured with the European Quality of Life-5 Dimensions (EQ-5D-3L) at the final visit. Secondary endpoints include overall mortality, long-term functional outcome, and target-level achievement in risk factor management.DiscussionThis long-term follow-up will provide evidence on whether the pragmatic post-stroke/TIA intervention program STROKE-CARD is capable of preventing recurrent cardiovascular events and improving quality-of-life in the long run.Trial registration clinicaltrials.gov: NCT04205006 on 19 December 2019.

Use of the Superior Breast Border Landmark for Planning Reduction Mammoplasty

Aims: The aim of this study was to evaluate the reliability of the upper breast border (UBB) in determining the new location of the nipple and to objectively analyze long-term nipple position compared to pre-operative markings. Patients and Methods: Thirty-eight patients (76 breasts) patients who underwent superomedial pedicle, reverse-T scar breast reductions and who had long-term (&gt;12 months) follow-up data were included. The sternal notch to the nipple, nipple to inframammarian fold (N-IMF), nipple to chest midline, and areola diameter were measured and recorded at the time of preoperative, markings, and long-term follow-up visit. Statistical Analysis Used: The differences in measurements were compared using a paired, two-tailed T-test, and a P &lt; 0.05 was considered statistically significant. Results: The average follow-up time was 17.9 months (range 12–41 months). The nipple was located, on average, 0.95 cm lower on postoperative assessment compared to preoperative marking (P = 0.060). The nipple was located, on average, 0.75 cm lateral on postoperative assessment compared to preoperative marking (P &lt; 0.001). The average postoperative increase in the N-IMF distance between marking and the long-term follow-up visit was 1.75 cm (P &lt; 0.001). The areola diameter was increased 0.21 cm on postoperative assessment compared to preoperative marking (P &lt; 0.001). Conclusions: The nipple position moved down and the N-IMF distance was greater than planned. However, the nipple was usually located at the area of the greatest projection of the breast due to almost equal elongation of the superior and inferior poles. The outcome of breast reduction procedures in which the postoperative nipple position is planned using the UBB was good.