Clinical Stability Research Articles

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

What Are the Psychosocial Effects of Pavlik Harness Treatment? A Prospective Study on Perceived Impact on Families and Maternal-Infant Bonding.

The Pavlik harness (PH) is the most common treatment for infants with developmental dysplasia of the hip. Although success rates are high when used appropriately, brace treatment may impact family function and parental bonding. The purpose of this study was to prospectively determine how PH treatment affected these psychosocial variables. This is a prospective, single-surgeon study at a tertiary-care, urban, academic children's hospital between November 2022 and March 2023. All patients newly treated with a Pavlik were eligible. Caregivers were administered the Postpartum Bonding Questionnaire and the Revised Impact on Family Scale (rIOFS) at the baseline visit and 2- and 6 weeks following treatment initiation. Demographic and treatment-specific information was collected through surveys and retrospective chart review. Descriptive statistics and bivariate analysis were used. A total of 55 caregiver-child dyads were included in the final analysis. Most patients were female (89%) and/or first-born (73%). Forty (73%) hips were diagnosed as having stable dysplasia. rIOFS scores steadily improved from baseline, through 2- and 6 weeks posttreatment initiation. Six-week rIOFS scores were significantly lower than both baseline ( P= 0.002) and 2 weeks ( P =0.018). Average parental bonding scores also improved steadily throughout treatment and did not surpass the threshold of clinical concern at any time. Neither full-time harness use (24h/d vs. 23h/d based upon clinical stability) nor age at treatment initiation had a statistically significant effect on parental bonding or family functioning (all P >0.05). Additional demographic variables such as birth order, parental history of anxiety/depression, and relative socioeconomic disadvantage also had no significant effect on psychosocial outcomes. PH treatment did not significantly impact maternal-fetal bonding or family dynamics. Relative to other pediatric diseases, PH treatment has an impact on family life greater than that of single-leg spica, but less than that of school-age children with chronic medical illnesses. As PH treatment is a widely used treatment for infantile developmental dysplasia of the hip, this study provides information that clinicians may use to more accurately counsel families and assuage parental concerns. Level IV-prospective uncontrolled cohort study.

Post Operative Management in Intensive Care of Obstructive Jaundice caused by Choledocholithiasis: A Case Report

Introduction: Gallstones are a very common problem in the global population. 10%-25% of affected people may have specific symptoms, and 1%-2% of them may experience major complications.
 Case presentation: 83-year-old female patient complained of yellow in her eyes and skin. Patients also felt pain in the right upper abdomen. Laboratory examination revealed increased bilirubin serum. Abdominal Ultrasound examination showed Obstruction of the Bilier Ductus caused by a stone at ductus sisticus and sludge of the gallbladder. The patient was diagnosed with Jaundice obstruction caused by obstruction of the bile ducts due to a stone at the ductus sisticus with a history of nephrectomy, Hypertension, and type 2 diabetes. The patient underwent Laparoscopic cholecystectomy, ERCP, and stent biller, After the procedure, the patient was admitted to the intensive care unit.
 Conclusion: Understanding the patient's comprehensive medical and surgical history is fundamental in understanding the postoperative patient in the intensive care unit. Adequate resuscitation is necessary for good clinical perfusion and physiological stability of the patient.

SAT324 Pulmonary Embolism Before And After Transsphenoidal Surgery In Cushing's Disease: Case Report.

Abstract Disclosure: A.B. Figueiredo: None. C.A. Baptista: None. C.R. Xavier: None. A.K. Nascimento: None. R.L. Dolci: None. A.L. dos Santos: None. J. Ethel: None. C.T. da Silva: None. N.M. Scalissi: None. J.V. Lima: None. Introduction: Patients with Cushing's syndrome (CS) have a 4-fold increased risk of thrombosis, due to increased synthesis of Von Willebrand factor and cortisol-stimulated fibrinogen, as well as increased synthesis of type 1 plasminogen activator inhibitor. The first 4 weeks after surgery are the period most susceptible to thromboembolism due to the worsening of the coagulation profile associated with the sudden reduction in the level of cortisol and its anti-inflammatory activity, leading to a thrombotic and inflammatory state. Case report: A 28-year-old woman, evaluated for bariatric surgery, was admitted to the emergency department complaining of dyspnea and palpitations that had started the day before. Supplementary oxygen therapy was instituted, the electrocardiogram showed a S1Q3T3 pattern, and chest angiotomography identified a thrombus in the arch of the right pulmonary artery and another in the left pulmonary artery. Thrombolysis was performed in the emergency room, followed by anticoagulation with intravenous heparin, resulting in clinical stability. He had typical symptoms of hypercortisolism such as obesity, early-onset hypertension, hirsutism, amenorrhea, and proximal weakness. During preparation for bariatric surgery, CS was suspected, with suppression test with dexamethasone and nocturnal salivary cortisol confirming hypercortisolism, and peripheral test with DDAVP and pituitary magnetic resonance imaging (MRI) confirming Cushing's disease by 8x4 mm adenoma. It was opted for clinical treatment with ketoconazole and anticoagulation for 6 months with transsphenoidal surgery. In the immediate postoperative period, it was planned to keep the patient off anticoagulants for the shortest possible time, with enoxaparin being restarted after surgery. On the 5th postoperative day, laboratory tests revealed cortisol of 1.7 mcg/dL and ACTH of 6.3 pg/mL, suggesting remission of the disease and supplementation with prednisone. On the 8th postoperative day, the patient complained of sudden dyspnea and desaturation, which led to the investigation of a new episode of pulmonary embolism. which was confirmed by chest angiotomography. Thus, a new Pulmonary Embolism was confirmed, this time with the use of full dose enoxaparin. The patient was referred to the ICU, where he received oxygen support and heparin infusion, with gradual clinical improvement and later, with anticoagulation for Warfarin with an INR goal of 2.5-3.0 and after 22 days of surgery, the patient achieved clinical stability and was discharged from the hospital. Conclusion: This case highlights the association of CS and thromboembolic events, especially Pulmonary Embolism. Presentation: Saturday, June 17, 2023

THU654 The Use Of Plasmapheresis In A Severe Case Of Amiodarone Induced Thyrotoxicosis

Abstract Disclosure: T. Moazezi: None. C. Koh: None. Thyroid storm is an endocrine emergency that results in a hypermetabolic state due to excess levels of circulating thyroid hormone and carries a high mortality rate. Therapeutic plasma exchange (TPE) can be used in cases of thyrotoxicosis refractory to medical management to achieve hemodynamic and clinical stability. We present a case of a 74-year-old male with severe amiodarone-induced thyrotoxicosis who presented with altered mentation and ultimately required intubation and intensive care for management of thyroid storm. Standard medical therapy for treatment was initiated immediately with antithyroid drugs, beta blockers, glucocorticoids, potassium iodide solution, and cholestyramine. However, the patient remained unresponsive and intubated with worsening biochemical parameters with increased total T3 levels and sustained elevated levels of free T4 even after five days of maximal medical therapy. Due to the lack of a clinical and biochemical response to conventional medical therapy, the patient was started on plasmapheresis and underwent a total of seven cycles of plasmapheresis over a period of ten days. He significantly improved with TPE and was successfully bridged to a total thyroidectomy, which was completed without complications. Our case demonstrated a decrease in total T3 concentration of roughly 45% after one session of plasmapheresis and roughly 76% with seven sessions of plasmapheresis by the time of thyroidectomy. Free T4 levels remained elevated above reference range until the day after the fifth session of plasmapheresis. This case is important because the literature surrounding the use of TPE in thyroid storm is sparse, and there have only been case reports and retrospective studies published on the subject. Ultimately, while TPE is not conventionally used as part of routine treatment for thyroid storm, endocrinologists should keep this tool at the forefront of their management strategies to deliver quicker treatment to critically ill patients and prevent complications of thyroid storm. Nonetheless, more research is needed to delineate concrete guidelines and specific protocols for use of TPE in thyroid storm. Presentation: Thursday, June 15, 2023

THU093 Pituitary Enlargement And Hypopituitarism In Patients Treated With Immune Checkpoint Inhibitors: Two Sides Of The Same Coin?

Abstract Disclosure: S. Menotti: None. S. Chiloiro: None. A. Giampietro: None. A. Bianchi: None. F. Angelini: None. T. Tartaglione: None. G. Antonini Cappellini: None. F. De Galitiis: None. E. Rossi: None. G. Schinzari: None. A. Scoppola: None. A. Pontecorvi: None. L. De Marinis: None. M. Fleseriu: None. Introduction: Immune checkpoint inhibitors hypophysitis (IIHs) represents an emerging problem in cancer patients treated with immune checkpoint inhibitors (ICIs). In this study, we aimed to describe the clinical and molecular features, therapeutic management and outcome of a multicentre series of IIHs. Material and Methods: Demographic and clinical features were retrospectively collected for all cases. Patients with new onset of pituitary disfunction during ICI treatment underwent contrasted pituitary magnetic resonance images (MRI). IIH was diagnosed if presence of typical radiological finding of hypophysitis. The immunotherapy induced hypopituitarism was defined as patients without the radiological finding of hypophysitis. Anti-pituitary and anti-hypothalamus autoantibodies were also measured. Results: Nine patients were included; 7 with metastatic melanoma, 1 metastatic lung adenocarcinoma and 1 metastatic kidney adenocarcinoma. Six patients were treated with nivolumab and three with ipilimumab. All patients had new-onset asthenia. Secondary hypoadrenalism was diagnosed in all patients. Pituitary MRI showed pituitary enlargement in 2 cases and no abnormalities in the other 7 cases. APA were positive in 57.1% and AHA in 85.7% of cases. Multidisciplinary treatments were established by neuro-endocrinologist and oncologists: all patients were treated with hydrocortisone replacement; ICI was withdrawn in 2 cases, until the clinical stabilization of the hypoadrenalism. None of the patients were prescribed immunosuppressive high dose glucocorticoids (over 40 mg /day). At follow-up, hypoadrenalism persisted in all cases. Pituitary enlargement (hypophysitis per se) on MRI spontaneously recovered in the two affected patients. We found that the typical features of hypophysitis involved more frequently females in our study and in patients treated with ipilimumab. Conclusion: Although this study did not clarify if autoimmune secondary hypoadrenalism and ICI hypophysitis on brain imaging are two sides of the same disease, our preliminary data underline the need for molecular studies of IIHs and of autoimmune ICIs-related hypopituitarism, especially central hypoadrenalism. Presentation: Thursday, June 15, 2023

Assessing Sustained B-Cell Depletion and Disease Activity in a French Multiple Sclerosis Cohort Treated by Long-Term IV Anti-CD20 Antibody Therapy

Few studies have investigated sustained B-cell depletion after long-term intravenous (IV) anti-CD20 B-cell depleting therapy (BCDT) in multiple sclerosis (MS) with respect to strict and/or minimal disease activity. The main objective of this study was to investigate how sustained B-cell depletion after BCDT influences clinical and radiological stability as defined by “no evidence of disease activity” (NEDA-3) and “minimal evidence of disease activity” (MEDA) status in MS patients at 12 and 18 months. Furthermore, we assessed the frequency of serious adverse events (SAE), and the influence of prior lymphocytopenia-inducing treatment (LIT) on lymphocyte subset counts and gammaglobulins in MS patients receiving long-term BCDT. We performed a retrospective, prospectively collected, study in a cohort of 192 MS patients of all clinical phenotypes treated by BCDT between January 2014 and September 2021. Overall, 84.2% and 96.9% of patients attained NEDA-3 and MEDA status at 18 months, respectively. Sustained CD19+ depletion was observed in 85.8% of patients at 18 months. No significant difference was observed when comparing patients achieving either NEDA-3 or MEDA at 18 months and sustained B-cell depletion. Compared to baseline levels, IgM and IgG levels on BCDT significantly decreased at 6 months and 30 months, respectively. Patients receiving LIT prior to BCDT showed significant CD4+ lymphocytopenia and lower IgG levels compared to non-LIT patients. Grade 3 or above SAEs were rare. As nearly all patients achieved MEDA at 18 months, we suggest tailoring IV BCDT after 18 months given the occurrence of lymphocytopenia, hypogammaglobulinemia, and SAE after this time point.

Real-life safety and effectiveness outcomes of teriflunomide in patients with relapsing–remitting multiple sclerosis: The TERICAM study

Introduction and objectiveTeriflunomide is an oral immunomodulatory agent approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). We examined teriflunomide outcomes in patients with RRMS under clinical practice conditions in Spain. Material and methodsNon-interventional, retrospective study at 15 sites in the Autonomous Region of Madrid and nearby regions. Effectiveness (relapses, EDSS, gadolinium-enhancing T1 lesions and new/enlarged T2-weighted lesions), safety (adverse events), and reasons for discontinuation during the 24 months after teriflunomide initiation were reported. ResultsA total of 776 patients were included (mean [SD] age was 43.3 (9.8) years; 69.3% were female). Two-thirds (67.7%) of patients had received a prior treatment, with beta-interferons or glatiramer acetate (BRACE) as the most frequent (93.5%) treatment. After 24 months, teriflunomide significantly reduced the annualized relapse rate (ARR) by 72% (mean [95% confidence interval] 0.12 [0.10, 0.14] vs 0.43 [0.40, 0.47] at baseline; P<.0001) and 81.8% of patients were relapse-free. The number of patients with gadolinium-enhancing T1 lesions and new/enlarged lesions on T2 was also reduced after 24 months of teriflunomide treatment (P<.001). Mean EDSS (SD) score was 1.9 (1.5) at teriflunomide initiation and 2.0 (1.6) at month 24. Half of patients (n=388) reported at least 1 adverse event (AE; gastrointestinal disorders: 26.2%; hair thinning: 25%; and elevation of ALT values: 12.9%). Most patients (91.5%) did not show fatigue increase during teriflunomide treatment. Among patients who discontinued treatment (n=262; 34.2%), the most common reasons were lack of effectiveness (58.0%), AEs (31.9%; n=82), and pregnancy desire (6.6%; n=17). ConclusionsMost RRMS patients treated with teriflunomide in clinical practice had received prior treatments. Teriflunomide resulted in decreased clinical and radiological activity and disability stabilization. AE frequency and type were in line with prior reports. Most patients did not experience fatigue increases after teriflunomide initiation.

Current development in surgical techniques, graft selection and additional procedures for anterior cruciate ligament injury: a path towards anatomic restoration and improved clinical outcomes-a narrative review.

Anterior cruciate ligament (ACL) reconstruction has been widely used for ACL injury for a long time. However, residual rotational instability and osteoarthritic changes after ACL reconstruction have been identified as problems. Thus, anatomic reconstruction techniques, various types of grafts and additional procedures have been desired to improve the clinical outcomes and knee instability. Although clinical outcomes and knee stability are better than in the past, ipsilateral graft failures still occur in 4-17% and osteoarthritic changes are seen in about 20% of patients after ACL reconstruction. To remedy these problems, it is necessary to improve the understanding of various surgical techniques and grafts and to pursue further improvement of surgical techniques. Therefore, the objective of this review is to summarize the advantages and disadvantages of various surgical techniques and graft selection, and additional procedures for ACL injury. A literature review was conducted on the surgical procedures for ACL injury. Recent trends in surgical techniques, graft selection, and additional procedures for ACL injury were described. We performed a literature search in PubMed for studies published from origin to May 8, 2023. Studies were required to be English-language articles. Although many reports indicate that double-bundle ACL reconstruction is comparable to anatomic single-bundle (SB) reconstruction, intraoperative complications such as tunnel coalition exist in double-bundle reconstruction, and the technique needs to be improved. ACL repair has shown good short-term results, but long-term results need to be examined in the future. Quadriceps tendon autograft is being used more frequently, but hamstrings tendon autograft and bone-patellar tendon-bone autograft also have good results. In addition, in higher-risk cases, lateral extra-articular tenodesis (LET) and anterolateral ligament (ALL) reconstruction can be performed with good results. To further improve clinical outcomes, more anatomical reconstructions should be pursued. Autografts are better than allografts and synthetic grafts, but further study is needed to determine which graft is better. Additional procedures should be performed in highly unstable cases and in revision cases.

Three-dimensional customized titanium plate versus conventional titanium miniplate for management of mandibular angle fractures

Background Surgical treatment of mandibular angle fractures using an internal fixation has changed in the last decades to achieve the required rigidity, stability, and immediate restoration of function. Purpose The aim of the study was to evaluate both clinically and radiologically the efficacy of three-dimensional customized titanium plate versus conventional titanium miniplate in the management of mandibular angle fractures. Patients and methods Sixteen adult patients with unilateral mandibular angle fracture indicated for reduction and internal fixation were selected from the Outpatient Clinic, Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Tanta University. Patients were divided into two equal groups according to the type of plating system used in fracture fixation, for group I mandibular angle fractures were fixed with 3-D customized titanium plate while for group II mandibular angle fractures were fixed with single conventional titanium miniplate. Postoperative clinical and radiographic evaluations were performed immediately, one week, two weeks, one month, three months and six months. The postoperative clinical evaluation included presence or absence of infection, position and stability of the mandibular lower border, state of occlusion, maximal mouth opening, sensory nerve function, condition of teeth related to the fracture line and patient's tolerance to the plate. The postoperative radiographic examinations evaluated the accuracy of reduction and bony union by measuring the inter-fragmentary gap and the intergonial distance. Results Uneventful wound healing was obtained in all cases of both groups except case no 4 of group II in which dehiscence and mild infection was happened. Satisfactory occlusion was obtained in all cases of both groups except case no 7 of group II where it had mild occlusal derangement. Other parameters including clinical stability, maximal mouth opening, sensory nerve function, and plate tolerance were comparable in both groups. There were no significant differences between group I and group II regarding inter-fragmentary gap and intergonial distance regarding postoperative radiographs. Conclusion The use of three-dimensional customized titanium plate and conventional titanium miniplate fixation systems provided enough stability for proper bone healing, establishment of optimal occlusion, and early return to normal function.

Long term outcomes in patients with anti-DPPX autoimmunity

DDPX antibody-associated encephalitis is characterized by cognitive dysfunction, neuropsychiatric symptoms, and CNS hyperexcitability, preceded by prodromal weight loss and diarrhea. Data regarding long-term outcomes is scarce. We retrospectively identified six anti-DPPX encephalitis patients across all three Mayo Clinic sites with inclusion criteria: 1) positive DPPX cell-based assay and mouse tissue-based immunofluorescence samples in both serum and CSF; 2) duration of follow up of at least 36 months from symptom onset to last follow up. Only one patient had a paraneoplastic process in the setting of chronic lymphocytic leukemia. At last follow up, all patients had resolution of GI symptoms. Residual cognitive impairment was seen in 4/6 (67%). Clinical stability was reached in 3/6 (50%) while on immunotherapy. Immunotherapy was discontinued in 2/6 (33%) and they remained stable without relapse at last follow up. One patient died of unclear etiology. Overall long-term outcomes are good in anti-DPPX encephalitis. Symptoms can improve on immunotherapy, but full resolution and return to premorbid baseline is unlikely.

The Risk of Growth Disturbance Is Low After Pediatric Anterior Cruciate Ligament Reconstruction With a Femoral Growth Plate Sparing Technique

To evaluate radiological tibial and femoral length and axis growth disturbances, as well as clinical outcome in skeletal immature anterior cruciate ligament reconstruction (ACLR) patients treated with a femoral growth plate-sparing ACLR technique. Skeletally immature patients who underwent operation between 2013 to 2019 with ALCR using the femoral growth plate-sparing technique were investigated with follow-up after growth plate closure. The inclusion criteria were isolated ACL rupture in patients with open physis in the distal femur and proximal tibia seen at plain radiography. The minimum follow-up time was 29 months. Patients were evaluated with full extremity radiographs measuring limb length discrepancy and coronal knee alignment compared to contralateral leg, as well as clinical evaluation with Rolimeter measurements and the Knee Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee subjective knee form (IKDC), and Tegner Activity Scale scores. Sixty-five patients were examined with radiography, and 52 patients were assessed with clinical examination. The mean follow-up time was 68 (range, 29-148) months. No limb-length discrepancy (-0.65 mm [confidence interval {CI},-2.21 to 0.92]) or angular deformity at tibia (-0.25° [CI,-0.78° to 0.28°]) was found. There was a small but statistically significant different angular deformity at the distal femur compared to the contralateral leg (-1.51° [CI,-2.31 to-0.72]) at follow-up. The side-to-side difference in knee laxity at follow-up was 2.4 mm. At follow-up the KOOS Sport, KOOS Quality of Life (QoL), IKDC, and Tegner scores were 80, 75, 86, and 5, respectively. Sixty-seven percent of the patients met the Patient Acceptable Symptom State, and 52% reported results exceeding the KOOS Sport MCID Level and 69% the KOOS QoL level. Femoral physis-sparing ALCR is associated with a low risk of alignment and length disturbances. The technique provides otherwise good subjective clinical outcome and knee stability. Level IV, therapeutic case series.

Four-flanged polypropylene optic piercing technique for scleral fixation of multifocal intraocular lens

BackgroundTo evaluate the feasibility of creating flanges using an optic piercing technique with a 6 − 0 polypropylene monofilament for scleral fixation of dislocated one-piece diffractive multifocal intraocular lenses (IOLs).Study DesignExperimental study and case series.SubjectsOptical bench test and eyes with IOL dislocation.MethodsTwo separate 6 − 0 polypropylenes were penetrated twice at the opposite peripheral optic of the TECNIS Synergy IOL (Johnson & Johnson Vision). The root mean square of the modulation transfer function (MTFRMS), at between + 1.00 and − 4.00 D of defocus, was measured in the TECNIS Synergy IOL both with and without optic piercing in the optical bench study. This case series included three eyes from two patients who underwent scleral-fixation of multifocal IOLs using the four-flanged polypropylene optic piercing technique. The postoperative corrected distance visual acuity (CDVA) at 4 m, the uncorrected near visual acuity (UNVA) at 40 cm, and IOL centration were evaluated.ResultsThe optical bench test showed no differences in MTFRMS values measured in the TECNIS Synergy IOL, either with or without optic piercing at all defocuses. In all three case series, the postoperative CDVA at 4 m was 20/20 and UNVA at 40 cm was J1. Postoperative anterior segment photographs showed good centration of IOLs in all cases.ConclusionThe four-flanged polypropylene optic piercing technique for multifocal IOL scleral fixation can provide excellent clinical outcomes and IOL stability after surgery without diminishing the performance of the multifocal IOLs.

Improvements in Treatment Adherence after Family Psychoeducation in Patients Affected by Psychosis: Preliminary Findings.

(1) Background: Family psychoeducation is a well-recognized intervention which aims to improve the outcomes of illness in patients affected by psychosis. It has benefits in treatment adherence and leads to a reduction in relapses, higher levels of patient insight, and lower levels of stress within the family and among caregivers. (2) Methods: Eight patients and their families were recruited and randomly assigned to a Falloon-based family psychoeducation (FPP) intervention, and nine patients and their families were randomized to a Gestalt-based family intervention (GT). We compared the outcomes of these two treatment groups at a baseline assessment (T0), at the end of the programs (T1), and 6 and 12 months after the end of the programs (T2 and T3). The assessments included examinations of cognition (The Mini-Mental State Examination (MMSE) and The Five Point Test (5 Point)), the psychopathology and severity of illness (The Brief Psychiatric Rating Scale (BPRS), The Positive and Negative Syndrome Scale (PANSS), and The Clinical Global Impression Scale (CGI)), expressed emotion in families (Expressed Emotionality (Family Questionnaire-EE)), patient quality of life (The World Health Organization Quality of Life-BREF (WHOQOL-B)), social functioning (The Personal Social Performance (SPS)), aggression (Modified Overt Aggression Scale (MOAS)), and treatment adherence (The Brief Medication Adherence Report Scale (BMARS)). The primary aim was to test whether the FFP vs. GT program was more effective in improving treatment adherence over time. (3) Results: treatment adherence improved much more in the FFP group over time at any follow-up: +43.1% at T1, +24.0% at T2, and +41.6% at T3. Other characteristics, including psychopathology and the clinical stability of the subject, did not change over time. (4) Discussion: Family psychoeducation based on the Falloon program was effective at improving treatment adherence and contributed to avoiding relapses in the long term. Further studies on larger samples should be conducted to confirm this evidence, and similar psychoeducational programs should be routinely promoted in the clinical setting.

C6 (Clinical Case) A 5-Year-Old with Headbanging and Hemiparesis

Abstract Introduction/Background A 5-year-old boy had a medical history of Phelan-McDermid syndrome; and with that associated autism spectrum disorder; severe, medication-resistant headbanging; and type 1 diabetes. He presented to community hospital with acute onset inability to walk, irritability, and vomiting. Case Description On examination he had left arm weakness and truncal ataxia. CT head identified a left cerebellar infarction. He was transferred to the local children’s hospital, and CT angiogram showed left PICA proximal occlusion. Due to diagnostic delay, the infarct was not amenable to endovascular intervention. Initial management was neuroprotective care, and given his history of headbanging and the risk of further trauma, only ASA monotherapy. MR brain visualized a left vertebral artery dissection, the stroke’s likely cause. Other causes were ruled out with normal echocardiogram and thrombophilia work-up, including antiphospholipid panel. Genetic analysis was negative for connective tissue diseases, bleeding or clotting disorders. On day 5 of admission, he acutely developed worsened left arm weakness and inability to bear weight. Repeat brain imaging showed new bilateral medial thalamic infarcts and diffusion restriction within the right putamen. Given this progression, despite the risk of bleeding, heparin was initiated. On day 9, repeat CT head identified a new lacunar infarct. On day 14, repeat MRI confirmed clinical stability, and he was switched from heparin to enoxaparin. After 27 days, he was discharged for home-based rehabilitation. His three-month follow-up MRI was stable, and anticoagulation was discontinued, while he remained on ASA only. Discussion There is no known association between Phelan-McDermid syndrome and cerebrovascular diseases. However, self-injurious behaviour, such as head banging, is not uncommon in the paediatric population, particularly among neurodiverse patients. These behaviours, in and of themselves, can cause significant injury and morbidity. The case shows how severe headbanging may have caused vertebral artery dissection with thromboembolic consequences. As such, for patients who demonstrate self-injurious behaviour, it is important to counsel these patients and families on potential harms, and inform efforts to mitigate risk, where possible. In cases of acute change to neurological status, stroke should remain on the differential diagnosis, and brain imaging should be considered. Time to central imaging affects therapeutic opportunities, as exemplified in this case where, due to delays in obtaining imaging, endovascular therapy was not an option for the patient. Conclusion Many children engage in self-injurious behaviour that can, as in this case, cause devastating consequences. Clinicians should remain wary of change in neurologic status and have low thresholds for central nervous system imaging, especially for patients with non-verbal communication.

Report and follow-up on two new patients with congenital mesoblastic nephroma

BackgroundTumors are rare in neonatal age. Congenital mesoblastic nephroma (CMN) is a usually benign renal tumor observed at birth, or in the first months of life. It may also be identified prenatally and associated with polyhydramnios leading to preterm delivery. Effective treatment is surgical in most cases, consisting in total nephrectomy. In literature, very few studies report on the neonatal management of such a rare disease, and even less are those describing its uncommon complications.Cases presentationWe report on two single-center newborns affected with CMN. The first patient is a preterm female baby, born at 30+ 1 weeks of gestation (WG) due to premature labor, with prenatal (25 WG) identification of an intra-abdominal fetal mass associated with polyhydramnios. Once obtained the clinical stability, weight gain, instrumental (computed tomography, CT, showing a 4.8 × 3.3 cm left renal neoformation) and histological/molecular characterization of the lesion (renal needle biopsy picture of classic CMN with ETV6-NTRK3 translocation), a left nephrectomy was performed at 5 weeks of chronological age. The following clinical course was complicated by intestinal obstruction due to bowel adherences formation, then by an enterocutaneous fistula, requiring multiple surgical approaches including transitory ileo- and colostomy, before the conclusive anastomoses intervention. The second patient is a 17-day-old male term baby, coming to our observation due to postnatal evidence of palpable left abdominal mass (soon defined through CT, showing a 7.5 × 6.5 cm neoformation in the left renal lodge), feeding difficulties and poor weight gain. An intravenous diuretic treatment was needed due to the developed hypertension and hypercalcemia, which regressed after the nephrectomy (histological diagnosis of cellular CMN with ETV6-NTRK3 fusion) performed at day 26. In neither case was chemotherapy added. Both patients have been included in multidisciplinary follow-up, they presently show regular growth and neuromotor development, normal renal function and no local/systemic recurrences or other gastrointestinal/urinary disorders.ConclusionsThe finding of a fetal abdominal mass should prompt suspicion of CMN, especially if it is associated with polyhydramnios; it should also alert obstetricians and neonatologists to the risk of preterm delivery. Although being a usually benign condition, CMN may be associated with neonatal systemic-metabolic or postoperative complications. High-level surgical expertise, careful neonatological intensive care and histopathological/cytogenetic-molecular definition are the cornerstones for the optimal management of patients. This should also include an individualized follow-up, oriented to the early detection of any possible recurrences or associated anomalies and to a better quality of life of children and their families.

The Retinal Phenotype Associated with the p.Pro101Thr BEST1 Variant

To describe the retinal phenotype associated with the p.Pro101Thr BEST1 variant. Retrospective, observational case series. Patients diagnosed with bestrophinopathies in which molecular genetic testing identified the p.Pro101Thr BEST1 as well as healthy carriers among their first-degree relatives. Medical records were reviewed to obtain data on family history and ophthalmic examinations, including retinal imaging. The imaging protocol included OCT and fundus autofluorescence using Spectralis HRA+ OCT (Heidelberg Engineering). Genetic analysis was performed by next-generation sequencing. Results of ophthalmic examinations and multimodal imaging features of retinal phenotypes. The c.301C>A, p.Pro101Thr BEST1 missense variant was identified as the causative variant in 8 individuals (all men) from 5 families, accounting for 13% of cases (8/61) and 10% of pathogenic alleles (9/93) in our cohort of patients affected by bestrophinopathies. Seven individuals (14 eyes) had the variant in heterozygous status: all eyes had a hyperopic refractive error (median spherical equivalent of+ 3.75 diopters [D]) and 4 individuals had a macular dystrophy with mildly reduced visual acuity (median of 20/25 Snellen), whereas the other 3 were asymptomatic carriers. On multimodal retinal imaging, 5 (36%) out of 14 eyes had subclinical bestrophinopathy, 4 (29%) had typical findings of adult-onset foveomacular vitelliform dystrophy (AOFVD), and the remaining 5 (36%) displayed a pattern dystrophy-like phenotype. Follow-up data were available for 6 subjects, demonstrating clinical stability up to 11 years, in both subclinical and clinical forms. An additional patient with autosomal recessive bestrophinopathy was found to harbor the p.Pro101Thr variant in homozygosity. The p.Pro101Thr BEST1 variant is likely a frequent cause of bestrophinopathy in the Italian population and can result in autosomal dominant macular dystrophies with incomplete penetrance and mild clinical manifestations as well as autosomal recessive bestrophinopathy. The spectrum of autosomal dominant maculopathy includes the typical AOFVD and a pattern dystrophy-like phenotype. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Biological Properties and Antimicrobial Potential of Cocoa and Its Effects on Systemic and Oral Health.

Cocoa is considered a functional food because it is a natural source of macro- and micronutrients. Thus, cocoa is rich in vitamins, minerals, fiber, fatty acids, methylxanthines and flavonoids. In addition to favoring the metabolism of lipids and carbohydrates, the bioactive components of cocoa can have an antioxidant, anti-inflammatory and antimicrobial effect, providing numerous benefits for health. This literature review presents an overview of the effects of cocoa, fruit of the Theobroma cacao tree, on systemic and oral health. Several studies report that cocoa intake may contribute to the prevention of cardiovascular, neurodegenerative, immunological, inflammatory, metabolic and bone diseases, in addition to reducing the risk of vascular alterations and cognitive dysfunctions. On oral health, in vitro studies have shown that cocoa extract exerted an inhibitory effect on the growth, adherence and metabolism of cariogenic and periodontopathogenic bacteria, also inhibiting acid production, glycosyltransferase enzyme activity and the synthesis of insoluble polysaccharides. Additionally, administration of cocoa extract reduced biofilm accumulation and caries development in animals infected with cariogenic species. Clinical studies also reported that the use of mouthwashes containing cocoa extract reduced Streptococcus mutans counts in saliva and dental biofilm formation. In short, these studies highlight the nutritional value of cocoa, considering its clinical applicability, stability and economic accessibility.

Prognostic Value of the Anatomic-Physiologic Classification in Adults With Congenital Heart Disease.

The prognostic role of the congenital heart disease (CHD) anatomic/physiologic classification has not been systematically studied. The purpose of this study was to determine whether CHD physiologic stage provided improvement in prognostic power (to predict all-cause mortality) beyond conventional clinical risk models. Retrospective study of adults with CHD at the Mayo Clinic (2003-2019). The CHD physiologic stage was assessed at baseline and 36 (24-48) months, and patients were classified into stages A to D at these time points. Clinical stability (remaining in the same stage), clinical improvement (moving to less advanced stage), and clinical deterioration (moving to more advanced stage) were determined at 36 months. We defined conventional clinical risk indices as age/sex, functional class, comorbidities, cardiac procedures, hepatorenal dysfunction, and ventricular/valvular dysfunction. Of 5321 patients, 1649 (31%), 1968 (37%), 1224 (23%), and 480 (9%) were in stages A, B, C, and D at baseline. Of 5321 patients, 4588 (86%) also had assessments at 36 months, and of these patients, 3347 (73%), 386 (8%), and 855 (19%) had clinical stability, deterioration, and improvement, respectively. Patients with clinical improvement were more likely to have undergone cardiac procedures between both assessments. Both baseline CHD physiologic stage (hazard ratio, 1.13 [95% CI, 1.09-1.17]; P<0.001, per unit increase in stage) and change in CHD physiologic stage (hazard ratio, 1.46 [95% CI, 1.32-1.61]; P=0.007, per unit increase in stage) were associated with mortality after adjustments for conventional risk indices and provided incremental improvement in prognostic power beyond conventional clinical risk models as evidence by an increase in C statistic from 0.702 (0.681-0.724) to 0.769 (0.754-0.787). The CHD physiologic stage can potentially be used for risk stratification, as well as to monitor disease progression and response to therapy.

Family Planning in Fertile-Age Patients With Multiple Sclerosis (MS) (ConPlanEM Study): Delphi Consensus Statements.

Family planning is essential for establishing Multiple Sclerosis (MS) prognosis, treatment decision, and disease monitoring. We aimed to generate an expert consensus addressing recommendations for family planning in MS patients of childbearing age. Initially, a committee comprising seven neurologists, experts in the MS field, identified the topics to be addressed. Then, the committee elaborated on different evidence-based preliminary statements. Next, using the Delphi methodology, a panel of neurologists manifested their level of agreement on the different statements using a Likert-type scale. Consensus was reached when ⩾70% of respondents expressed an agreement or disagreement using a five-point scale. Consensus was achieved on 47 out of 63 recommendations after three rounds of evaluations. The panel considered it essential to address family planning in all patients of childbearing age. There was also consensus that treatment should not be delayed due to the patient's desire for pregnancy. Additionally, in highly active patients, planning the pregnancy in the medium to long term using depletory drugs such as cladribine or alemtuzumab might represent a useful strategy. However, risks of adverse effects on the fetus due to drug-associated secondary autoimmunity should be addressed when alemtuzumab is considered. Moreover, the maintenance of natalizumab during pregnancy in very active patients reached expert consensus. Also, the panel supported the use of certain disease-modifying treatment(DMT) during lactation in selected cases. Our results identified specific areas of pregnancy planning in MS patients, where different treatment strategies might be considered to facilitate a safe and successful pregnancy while maintaining clinical and radiological stability.