Clinical Evolution Research Articles

Vaginal Rhabdomyosarcome: Case Report

Introduction: Rhabdomyosarcoma is a soft tissue sarcoma, most common in children, localised in the female genital tract and therefore rare in adults. Among its subtypes, it is most often distinguished as embryonal. It is an aggressive tumour, difficult to diagnose, is usually detected by CT or MRI and the diagnosis is confirmed by biopsy and treatment involving surgical excision, radiotherapy and chemotherapy. The authors present a case of embryonal rhabdomyosarcoma localised in the vagina, highlighting relevant aspects of the subject. Observation: We report the observation of a girl aged 2 years and 8 months, with no notable antecedents, from a 2nd degree consanguineous marriage. For 1 month she presented with a rapidly progressive vaginal mass associated with bleeding. Examination revealed a reddish, grape-like mass in the vulva. Abdomino-pelvic ultrasound revealed a vaginal tumour, abdomino-pelvic MRI revealed an endovaginal mass delivered through the vulva, suggesting a botryoid rhabdomyosarcoma, and biopsy of the vaginal mass with morphological appearance and immunohistochemical profile of an embryonal rhabdomyosarcoma. The extension work-up showed a vulvovaginal lesional process, with no secondary location on the thoraco-abdominal CT scan. The patient was classified as group C according to the RMS 2005 protocol and received 6 courses of IVA + vaginal brachytherapy + 3 courses of IVA with a good clinical and biological evolution. Conclusion: In view of the diagnostic difficulties and the risk of progression and rapid worsening of rhabdomyosarcoma, early positive diagnosis means that treatment can be started at an early stage with chemotherapy, surgery and radiotherapy.

Covid-19 in HIV-infected patients: A report of 14 cases experience of the infectious diseases department of the University Hospital Mohamed VI Marrakech - Faculty of Medicine and Pharmacy Marrakech

Objective: Evaluation of clinical, biological, radiological characteristics, therapeutic management and outcome in patients with HIV / SARS-COV-2 co-infection. Materials and Methods: Descriptive retrospective study of 14 files of patients with HIV / SARS-COV-2 co-infection confirmed by SARS-COV-2 PCR between April 2020 and May 2022 in the infectious diseases department of the University Hospital Mohamed VI Marrakech Results: 14 patients were included, with a sex ratio M/F: 2.5. The mean age of our patients was 40.7 years. The clinical symptoms presented by our patients were: asthenia (71%); febrile pneumonia (64.20%); anosmia (46.6%); diarrhea (28.5%); and lower limb thrombophlebitis (7.14%). The HIV status was as follows: 9 new cases (64.2%), while HIV was already present in 5 patients (35.8%). On the radiological level, 10 patients had moderate damage (72%), 3 patients had mild damage (21%), while 1 patient had severe damage (7%). Our patients' treatment changed during the study period; in particular, one group of patients was treated with the national covid-19 therapeutic protocol, while others received molnupiravir. The outcome was overall good, with a clear clinical and biological improvement; and only 4 patients died. Conclusion: The predisposition to SARS-COV2 infection as well as the clinical presentation and evolution of Covid 19 in PLHIV do not differ from the general population.

Superior capsular reconstruction with the long head of the biceps tendon achieves excellent clinical results and low rotator cuff rerupture rates one year after cuff repair surgery.

To analyze the clinical one-year evolution of healed and rerupture lesions in patients who received a rotator cuff repair plus Superior Capsular Reconstruction (SCR) with the long head of the biceps (LHB). Moreover, to compare this evolution between men and women. A pilot study was conducted on patients who underwent a rotator cuff repair plus SCR with LHB between February 2021 and June 2022. All patients completed pre-operative and one-year post-operative evaluations for tendon type of tear and tendon integrity using Magnetic Resonance Imaging (MRI)after one year of the surgery. Besides, functionality was evaluated with the American Shoulder and Elbow Surgeons (ASES) score; the visual analog scale for pain (VAS); and the Constant score. A total of 38 patients completed the one-year final evaluation, they presented an increased functionality score to 83 and 86 in Constant and ASES scales (p < .001), respectively. Besides, 84% of the patients presented a healed cuff, while rerupture occurred in 16% of the patients. There were differences between the healed and rerupture patients in the total Constant score, with a remarkable increase in the strength subscale, almost double for patients with healed cuff (p < .001); in the same way, daily life activity score, and balance subscale increased, while pain score decreased in the healed cuff group (p < .05). There was no difference in functionality between men and women (p > .05). Besides, almost all patients achieved the MCID in both ASES and Constant total scores, irrespectively of the healing group. The cuff repair using SCR with the LHB achieved a low percentage of rerupture and a functional improvement after one year of follow-up. Patients who healed the lesion presented more strength and better performance in daily life activities than those with cuff repurture. Thus, SCR + LHB procedure can be considered an efficient technique for rotator cuff repair surgery for both men and women. Although a comparison with a control group is needed to confirm these findings.

#992 Protocol based on PLA2R1 epitope recognition is superior to standard protocol in achieving remission in PLA2R1-associated membranous nephropathy

Abstract Background and Aims Membranous nephropathy (MN) is a rare, but severe autoimmune disease affecting kidney glomeruli. Clinical evolution is variable, ranging from spontaneous remission to persistent nephrotic syndrome and kidney failure. The major autoantigen in MN is PLA2R1 protein associated with 50-70% of all cases. Patients may present antibodies against a single immunodominant CysR domain or may develop additional antibodies against CTLD1 and/or CTLD7 and/or CTLD8 domains of PLA2R1 defining a cascade immunization or epitope spreading. The mechanism of epitope spreading has been described in a variety of contexts: it can reinforce immune response to eliminate a pathogen, but can also be associated with the aggravation of autoantibody-mediated autoimmune pathologies. The value of this marker in the management of MN patients remains debated. Our initial study (confirmed on an independent cohort) has shown that the single domain recognition (non-spreader patients) is associated with a higher chance of spontaneous remission (45% vs 0.05% in GEMRITUX cohort) and a better response to treatment (100% of remission regardless of the dose of rituximab used). The patients with multi domain recognition (spreader patients) of CTLD1 and/or CTLD7 domains, on the other hand, have poor prognosis and are less likely to achieve remission requiring high doses of rituximab. Based on these studies we have proposed a personalized treatment protocol with either low or high dose Rituximab based on patients’ PLA2R1 epitope spreading status. The aim of this study was to evaluate the efficacy of this personalized treatment in comparison to the established GEMRITUX protocol. Method A multicenter, randomized, controlled, prospective clinical trial was conducted in 12 French hospitals. Sixty-four consecutive patients with PLA2R1-related MN were randomly assigned to either the control group following the GEMRITUX protocol (symptomatic treatment for 6 months, two 375 mg/m2 rituximab infusions at month-6 in case of persistent nephrotic syndrome (NS)) or the personalized treatment (PMMN) group (patients with no epitope spreading at month-0 were treated as per GEMRITUX protocol, while patients with epitope spreading at month-0 or month-6 with persistent NS were treated immediately with two 1 g rituximab infusions). The primary study outcome was the rate of clinical remission at month-12. The secondary outcomes were complete and partial remission, immunological remission, proteinuria, albuminuria, serum creatinine, and PLA2R1 antibody titer. Results From 64 patients included, three were excluded from final analyses due to loss to follow-up. There was no difference in age, gender, albumin, UPCR, anti-PLA2R1 titer and the rate of PLA2R1 epitope spreading at baseline between the two groups. At M12, 34% of patients from the GEMRITUX group and 69% of patients from PMMN group achieved partial clinical remission (P = .0105) defined as UPCR &amp;lt; 3.5 g/g with a decrease greater than 50% from baseline; improvement or normalization of serum albumin; and increase of serum creatinine lower than 20%. While there was no difference in remission rate between the GEMRITUX group and PMMN group for patients with single domain recognition (38% vs 50%, respectively, P = .7107), multi-domain recognizers (spreaders) were more likely to achieve remission with personalized protocol (36% vs. 87%, P = .0078). The rate of complete clinical remission between the two experimental groups, defined as UPCR &amp;lt;0.3 g/g and normal albumin, was close to statistical significance (0% vs 16%, P = .0538). Conclusion Personalized treatment protocol based on the stratification of patients with PLA2R1-related MN according to their epitope spreading status, is superior to the standard GEMRITUX protocol in achieving partial clinical remission at 12 months. Patients with multiple domain recognition should be treated immediately with high doses of rituximab to increase their chances of remission.

#2968 Preemptive kidney transplantation: the best option for retransplantation?

Abstract Background and Aims Kidney re-transplantation (Re-KT) is associated with worse outcomes. Better results have been described when the KT is performed preemptive, before the patient returns to dialysis. However, the experience is limited so far. Method We performed a retrospective analysis of KT patients who received a preemptive KT (pRe-KT) in Andalusia between 1978-2023. A case-control study was carried out, choosing 2 controls for each case, adjusted for donor and recipient demographic characteristics (1 patient receiving a second non-preemptive KT [npRe-KT] and 1 patient receiving a first KT). We compared clinical characteristics and evolution between the 3 groups. Results During this period, 12217 KT recipients were registered in Andalusia. Of these, 1380 (11.3%) received at least a second KT. Eighty-two (0.059%) patients were pRe-KT recipients, all of them with a second KT. In the npRe-KT patients, there was a lower proportion of living donors than in the other groups (pRe-KT 30.4%, npRe-KT 6.3%, first KT 28.4%; p &amp;lt; 0.001). There were no differences nor in age neither in gender of donors and recipients. Graft survival in pRe-KT and first KT patients was similar and significantly better than in npRe-KT. Adjusting for donor type (living/deceased), npRe-KT remained as a risk factor. However, we observed no differences in patient survival between groups. Conclusion In pRe-KT patients, outcomes are significantly better than npRe-KT outcomes and similar to that of the first KT. These patients, when their clinical situation allows it, should be evaluated for inclusion on the waiting list before the definitive graft loss. Living donor KT should be actively encouraged in patients who are losing the functionality of their renal graft.

#2867 Is there an interrelationship between the SARS-CoV-2 virus and the BK polyomavirus in kidney transplant recipients?

Abstract Background and Aims Several viral co-infections following SARS-CoV-2 infection have been described. However, there is very limited and inconclusive data on the relationship between COVID-19 and BK polyomavirus (BKV) in kidney transplant (KT) recipients. Method Retrospective analysis of KT recipients with BK infection (BKi) in our centre from March 2020 (first cases of COVID-19) to March 2023. BK viremia is periodically determined prospectively in all KTs performed in our hospital. We carried out a case-control study, choosing two controls without BKi for each case (closest transplant date and similar donor and recipient age). We analyzed clinical characteristics and evolution, as well as previous history of COVID-19 in both groups. A composite outcome including de novo BKi and/or significant increase in BK viremia (increase &amp;gt; 50% in at least 2 consecutive samples) was analyzed. Multivariate analysis was performed using logistic regression for de novo BKi and/or significant increase in BK viremia risk factors. Results During this period 235 KTs were performed in our center, of which 37 were diagnosed with BKi (16.1%). The median time from the date of KT to BKi was 73 days. When comparing cases versus controls, demographic characteristics and donor type were similar in both groups, except for a higher proportion of males in the BKi group (76.3% vs. 55.3%; p = 0.029). The incidence of SARS-CoV-2 infection was significantly higher in patients with de novo/increased viremia BKi than in the control group (44.7% vs. 26.3% p = 0.048). During follow-up, one patient in the BKi group died and one patient in the control group lost the graft due to causes other than viral infections. In multivariate analysis, male gender and SARS-CoV-2 infection were risk factors for the composite outcome. Conclusion As has been described with other viruses, there may be an interrelationship between SARS-CoV-2 and BKV. Our experience suggests that close monitoring for BKV after episodes of COVID-19 may be appropriate.

#2771 Peritoneal dialysis after kidney graft loss … and now, what?

Abstract Background and Aims The evolution of peritoneal dialysis (PD) as renal replacement therapy (RRT) after graft loss is not well defined. Method Retrospective analysis of the Andalusian Renal Registry of patients who received their first kidney transplant (KT) in Andalusia (Spain) and returned to dialysis between 1978-2023. Patients who lost follow-up and those who underwent preemptive re-KT were excluded of the study. We compared clinical characteristics and evolution between those who started hemodialysis (HD) and peritoneal dialysis (PD) after graft loss. Secondly, we analyzed technique and patient survival in those who started PD post-KT versus patients on PD as their first renal replacement therapy (RRT) We performed multivariate analysis for PD technique and patient survival risk factors using Cox regression. Results During this period, we followed 11868 KT recipients in Andalusia. Of these, 3148 (26.52%) lost the graft: 2768 started HD and 298 PD. 82 patients underwent preemptive re-KT. Patients who returned to DP were younger (p &amp;lt; 0.001) and glomerulonephritis as cause of chronic kidney disease (CKD) was more frequent (p = 0.019). The pre-KT RRT was HD in 96.3% of patients starting HD post-KT and PD in 48.3% of patients who returned to PD after KT (p &amp;lt; 0.001). Survival of patients in the HD group was lower than those who started PD (p = 0.026). In the multivariate analysis, older age when dialysis restarted, male sex and diabetes were risk factors for patient death and not the type of dialysis. When comparing only the post-KT PD group (n = 298) versus patients on PD as their first RRT (n = 5312), patients on the first group were younger (57.1 vs. 41.9; p &amp;lt; 0.001) and time on PD was longer (24.4 vs. 19 months; p &amp;lt; 0.001). The causes of PD drop-out also varied between groups (p &amp;lt; 0.001). During this period, 269 post-KT PD patients left the technique mainly due to re-KT (34.3%) and in the PD group as the first RRT, there were 4919 technique drop-outs, mainly due to transfer to HD (35.3%) and death (30%). The percentage of peritonitis was higher in the post-KT PD group, although without significant differences (post-KT PD 27.9% vs. PD as first RRT 23.25%; p = 0.061). Survival of the DP technique in post-KT PD group was 78.2% at 1 year and 38.5% at 5 years, and 77.7% and 42.1% respectively in the DP group as the first DP RRT (p = 0.059). In the multivariate analysis, patient age and diabetes as a cause of CKD, behaved as risk factors for patient survival. Conclusion Almost half of the patients starting PD after KT had been on PD prior to transplantation. They tend to have more peritonitis although survival of the technique and complications were very similar to those observed in patients on PD as first RRT.

#1814 Infection associated pancreatitis in peritoneal dialysis, a case report

Abstract Background and Aims Peritoneal dialysis (PD) patients seem to have a higher incidence of acute alithiasic pancreatitis. Though rare and with some suggested triggers described in the literature, this is still a poorly understood and potentially life-threatening complication. We present a 60 years old woman concluding antimicrobial therapy with an icodextrin night-dwell regimen for peritonitis presenting with epigastric pain. This work reviews our approach to cloudy effluent from non-infectious causes during an infection while managing acute pancreatitis in the PD setting. We report diagnostic difficulties and treatment considerations with a positive outcome. Method We present a 60 years old woman on PD for one year presenting to the emergency room in November of 2023 with severe epigastric pain, nausea and emesis. She suffered from stage 5 chronic kidney disease due to autosomal dominant polycystic kidney disease and had disease complications as anemia and secondary hyperthyroidism controlled within targets. She was on automated PD (APD) with glucose based solutions. She was on the 17th of 21 days antibiogram guided treatment (ceftazidime) for a Enterobacter ludwigii PD-related peritonitis with good clinical evolution and peritoneal effluent (PE) leukocyte count per μl from 1258 to 91 in 5 days. In the previous 3 months she had had 2 other infectious episodes. A bacteremic urinary tract infection to E. coli associated with peritonitis treated with antibiogram guided therapy (ceftazidime) followed by C. difficile colitis treated with oral vancomycin. During each infection period she transitioned from APD to continuous ambulatory peritoneal dialysis with an icodextrin night dwell. On admission she presented with normal vital signs, no fever, and abdominal distention with severe epigastric tenderness to palpation without muscular guarding. Her dwell exchange showed blood-tinged cloudy PE. She had hemoglobin of 11.3 g/dl, otherwise normal blood cell counts, and raised amylase (213 UI/l) and lipase (1467 UI/l). There was no elevation of transaminases, cholestatic enzymes, C-reactive protein or procalcitonin and lipidemia or hyperbilirubinemia were normal. PE cell count showed 213/μl leukocytes and 202/μl erythrocytes. Abdominal ultrasound showed no evidence of an obstructive cause. She was admitted in the surgical care unit for a conservative and watchful approach. Results On presentation we accounted for the peritonitis still under treatment, acute pancreatitis, drug therapy and recently introduced icodextrin solution. The acute alithiasic pancreatitis diagnosis was established but there was still a possible causative role of icodextrin or infection and refractory peritonitis could also not be promptly excluded. The literature suggests icodextrin and other drugs as causes for acute pancreatitis in some patients but also mentions the possibility of cloudy or hemorrhagic effluent due to abdominal inflammation processes. Considering the clinical stability, the multiple possible contributing causative agents and the differential diagnosis of refractory peritonitis we closely monitored PE cell count evolution keeping the icodextrin dwell and ceftazidime prescriptions and collected samples for bacterial and fungal culture. The cultures were negative and stability of leukocyte count and mononuclear cell predominance (Fig. 1) helped us exclude the peritonitis hypothesis and attribute the PE changes to the pancreatitis process. Conclusion Inpatient monitoring and identifying all possible causes are essential to ensure good outcomes in PD patients suffering from acute pancreatitis. Full anamnesis, physical examination and close attention to laboratory findings were key in allowing adequate antibiotic therapy and resolution of the abdominal inflammatory process at hand while maintaining an adequate PD prescription.

#2840 Early tolerance of SGLT2i therapy in patients with ATTR V30M amyloidosis: staging the disease to establish standard of care

Abstract Background and Aims Studies of sodium-glucose co-transporter 2 inhibitors (SGLT2i) therapy on ATTR cardiomyopathy are scarce and focus wild-type and V122I. In ATTRv, namely V30M, SGLT2i introduction to preserve kidney function or improve cardiorenal syndrome is not an outlined practice. Our aim was to assess the clinical evolution and difficulties with SGLT2i therapy in ATTR V30M amyloidosis, a population with neurogenic bladder, dysautonomia and prone to dehydration. Methods Patients with ATTR V30M amyloidosis and criteria for SGLT2i started standard dosages. Gillmore score (GS) for ATTR cardiomyopathy, kidney failure risk equation (KFRE) and the renal system score (RSS) of the FASTEX model (Fabry disease) were calculated. Estimation of heart amyloid load was based on Tc-99-DPD scintigraphy. Results Eight patients were followed on median of 7 months [IQR 5.6-9.4]; 7 treated with dapagliflozin, 1 with empagliflozin. 6 had type-2 diabetes. 4 were treated with tafamidis, 1 inotersen and 1 patisiran. 3/7 had positive DPD scintigraphy. Heart failure decompensation, new arrhythmias and renal adverse events were absent. Neurogenic bladder was present in 4 patients, 2 had urinary tract infections. 1 had symptomatic hypotension, leading to discontinuation of therapy. EGFR and RSS improved in 5 and 3 patients, respectively; NT-proBNP/albuminuria/proteinuria and KFRE at 2 and 5 years decreased. In terms of cardiomyopathy, 1 patient improved to GSI; 2 using CKD-EPI creatinine and none using CKD-EPI cystatin C. 1 progressed to GSII in all equations. Conclusion In this pilot study, we evidenced that ATTR V30M patients meet the criteria for SGLT2i therapy. Dysautonomia and neurogenic bladder were not an impediment for therapy. In addition to disease modifying drugs, SGLT2i may improve kidney and cardiovascular outcomes in ATTR V30M amyloidosis.

#1337 Evolution of ANCA-associated vasculitis in a population with confirmed renal involvement. Myeloperoxidase and proteinase 3 antibodies, which is worse?

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare but potentially serious diseases with high mortality. Renal involvement is frequent in AAV with patients developing end-stage renal disease (ESRD) or becoming dependent on dialysis in up to 23% of patients. Several studies suggest the presence of clinical factors as predictors of survival in these diseases. The objective of this study was to analyze clinical evolution of AAV and to identify potential risk factors for developing renal events (ESRD or dialysis) and death in patients with AAV, with special attention to the implications that the presence of myeloperoxidase (MPO) or proteinase 3 (PR3) antibodies at diagnosis may have on the disease progression. Method We conducted a retrospective observational study of patients under follow-up for AAV. We considered only those with a confirmed diagnosis of AAV through renal biopsy for the present study. We collected clinical and laboratory variables at the time of disease presentation. We divided the patients based on the presence of MPO or PR3. Subsequently, we analyzed the patients' progression towards the occurrence of renal events (ESRD or dialysis) and mortality. Results Out of the 42 studied patients, 29 were MPO-positive and 13 were PR3-positive. We observed statistically significant differences in age and the frequency of hypertension, with the MPO group being older and more hypertensive than the PR3 group. On the contrary, PR3-positive patients exhibited a higher percentage of diabetes and increased severity of vasculitis at diagnosis as measured by the Birmingham Vasculitis Activity Score (BVAS). While most MPO-positive patients met criteria for microscopic polyangiitis (MPA), all PR3-positive patients met criteria for granulomatosis with polyangiitis (GPA) according to the ACR/EULAR 2022 guidelines. There were no statistically significant differences regarding clinical or laboratory variables analyzed, neither with induction nor maintenance treatment. We did not observe differences in the progression towards renal events or mortality between groups. However, we did observe a higher percentage of disease recurrence among PR3-positive patients (Table 1). Conclusion There were no statistically significant differences observed in the progression towards renal events (ESRD and dialysis) or mortality regardless of MPO or PR3 antibodies.

Double Localization of a Cerebral Germinoma: Case Report

Germinal cell tumors are embryonic tumors located mainly in the gonads, and their cerebral localization is rare, representing less than 1% of intracranial neoplasia. Clinical expression can be polymorphous, while imaging provides a highly suggestive radiological semiology. We report the case of a 31-year-old patient presenting with diabetes insipidus evolving for one year and associated with decreased visual acuity. Cerebro-medullary MRI revealed a tumoral process in the pineal region associated with thickening of the pituitary region. Tumor markers (β HCG and AFP) in plasma and CSF were negative, confirming the diagnosis of pure germinoma without the need for biopsy. Treatment is mostly based on radiotherapy, and sometimes on a combination of radiotherapy and chemotherapy. The latter was our therapeutic choice, with a good clinical and biological evolution.

Analysis of clinical outcomes in older individuals who received pharmaceutical care and posthospital discharge follow-up.

Previous evidence underscores the need to assess potential clinical outcomes resulting from pharmaceutical care interventions and to monitor patient's progress to evaluate their clinical evolution, which is crucial for bolstering the relevance of implementing pharmaceutical care in healthcare services. To conduct an in-depth analysis of pharmaceutical care practices in a geriatric ward and monitor the clinical outcomes of older people served. This interventionist study was conducted in the geriatrics ward of a Brazilian university hospital. The research intervention occurred between January and May 2022, with a follow-up conducted for up to 90 days after patients' hospital discharge. Older patients in the geriatrics ward received pharmaceutical care, including medication reconciliation, medication review,and pharmacotherapeutic follow-up, aimed at identifying and resolving drug-related problems (DRPs). The clinical relevance of DRPs and pharmaceutical recommendations was evaluated. Additionally, analyses were conducted on mortality and rehospitalization outcomes in older patients at 30, 60,and 90 days following initial hospital discharge. Of the patients evaluated, a significant 88.3% exhibited at least one DRP (with an average of 2.6 ± 1.9 DRPs per patient), with the majority classified as need/indication problems (38.9%). The acceptance rate of pharmaceutical recommendations was 80.9%, with the majority categorized as very significant relevance (60.4%). DRPs were predominantly of serious clinical relevance (50.9%). In patients whose clinical indicators could be monitored, 95.5% showed some clinical response (in vital signs, laboratory testsand/or clinical status evolution) potentially related to resolved DRPs. Association analysis revealed that a higher number of medications in use before hospitalization correlated with a greater identification of DRPs during hospitalization (p = 0.03). At hospital discharge, 23.6% of patients were no longer using polypharmacy. In total, 16 patients (26.7%) died during the study period. Among patients who did not die during hospitalization (n = 54), 20 patients (37%) experienced rehospitalizations within 90 days following discharge. This study facilitated the consolidation of pharmaceutical care implementation in a geriatric ward. We conducted identification, evaluation,and proposed evidence-based solutions, as well as monitored cases for outcome analysis. It is anticipated that this methodology will inspire future research and the implementation of pharmaceutical care-related services.

PARTIALLY REVERSIBLE DILATED CARDIOMYOPATHY ASSOCIATED WITH AMPHOTERICIN B THERAPY

Abstract Background Amphotericin B (AmB) is an antifungal drug commonly used in a broad spectrum of infections, including leishmaniasis. Leishmaniasis, transmitted through insect bites, has cutaneous, mucocutaneous, or visceral (particularly liver and spleen) involvement. The main adverse effects of AmB are cardiotoxicity and nephrotoxicity, often reversible, but with yet unclear pathophysiology. Reversible dilated cardiomyopathy is a rare disease with very few cases described in the literature (less than 10). The Case A 41–year–old man with a silent cardiological history (only cocaine and alcohol abuse in past) is admitted for visceral leishmaniasis. Cardiological evaluation: LBBB in ECG (none previous available); no abnormality detected on ECOCG (EF 55%). Ten days after the AmB cycle, onset of worsening dyspnoea needing hospital treatment after a further two weeks for heart failure (HF). At ECOCG severe left ventricular dysfunction (EF 30%), no rise of cardiac enzymes was detected. Coronary angiography showed 50–75% stenosis on RCA and LAD, treated by angioplasty and stenting. Cardiac MRI showed: dilated left ventricle with diffuse biventricular hypokinesis (FE 16% left and 22% right), areas of LGE of non–ischemic appearance. HFrEF GDMTs were prescribed, with progressive clinical improvement over the next four weeks; at cardiac MRI performed one month later, partially recovery of biventricular function (FE sn 41% right 48%) was found. The ECG showed regression of LBBB. No myocardial biopsy was performed, so it is not possible to get to an unequivocal cardiac dysfunction’s cause. However, the time relationship between the use of AmB and the clinical findings evolution, consistently with the few literature available, suggests a probable diagnosis of AmB toxic cardiomyopathy. An ischaemic cause of the dysfunction is unlikely by the MRI feature and by coronary angiography findings. Literature data suggest that the presence of predisposing factors for cardiac dysfunction, rather than the duration of treatment or preparation used, is the most relevant factor in the development of AmB–related cardiomyopathy. It’s important to perform cardiac monitoring in all patients receiving AmB therapy. In all reported cases, cardiac function recovered substantially after cessation of AmB treatment.

A COMPLEX CASE OF EARLY ONSET ATRIAL FIBRILLATION IN AN ENDURANCE ATHLETE: THE IMPORTANCE OF FAMILY HISTORY

Abstract Introduction Early onset atrial fibrillation (AF) in an endurance athlete represents a challenge for the cardiologist, especially in apparent absence of an overt structural heart disease. Different genetic variants have been associated with early onset AF but indications to genetic testing are still under definition. Case A 54–year–old man (BMI 19 kg/sqm), previous competitive athlete (Nordic running and walking) presented to the Emergency Department with sudden onset palpitations and dyspnea due to high penetrance AF (145 bpm). Family history (FH) was positive for cerebrovascular accidents in both parents and for early onset (&amp;lt;60 years) AF in the father. The man had a recent history of borderline hypertension, of effort related syncope of and of infundibular, isolated, premature ventricular complexes during a maximal exercise stress test (otherwise negative for ischemia) which ultimately led to the denial of competitive sport eligibility. Sinus rhythm (SR) was acutely restored with flecainide and the patient was discharged with low dose nadolol. Cardiac US showed normal left ventricular (LV) dimensions and thicknesses (10 mm), with regular LVEF (60%) and global longitudinal strain (–18%), mildly dilated left atrium (LAVI 36 ml/sqm) and bi–leaflet mitral valve prolapse without significant mitral regurgitation, mitro–anular disjunction nor Pickelhaube sign; 24h Holter ECG showed SR with rare supraventricular (SV) ectopic beats and a 4 beats SV run. Due to the recurrence of short episodes of palpitations, rhythm control with flecainide and antithrombotic prophylaxis were started and AF ablation was planned. Genetic testing for early onset AF identified a nonsense variant (c.84665delG; p.Gly28222fs*2) in TTN gene, classified as likely pathogenic (C4), so far not reported in scientific literature. Also, despite a moderate–low cardiovascular risk as assessed by SCORE2, mostly due to the FH and the desire to engage in high intensity exercise, coronary CT was prescribed, which showed a critical coronary disease leading to stenting on left anterior descending artery and intermediate branch. Cardiac MRI was planned. Conclusions Early onset AF in endurance athletes should not be underrated and a thorough examination including a detailed family history should be performed. TTN is the single gene most frequently associated with early onset AF in absence of an overt structural heart disease, but the subsequent clinical evolution is still largely unknown.

CHANGES IN LEFT ATRIAL VOLUME DURING ECHOSTRESS IN PATIENTS UNDERGOING MITRAL VALVE PLASTIC CARDIAC SURGERY

Abstract Mitral Regurgitation (MR) is characterized by a high morbidity and mortality that often finds a solution only in the reparative surgical treatment, in particular in presence of myxomatous degeneration that cause the prolapse of one or both leaflets. This results in an increase in diastolic pressure that leads to a progressive dilation of the left atrium. The increase in Left Atrium Volume Index (LAVI) during stress test represents a negative prognostic factor in the clinical evolution of many pathologies, such as ischemic heart disease, hypertrophic cardiomyopathy, heart failure. An increase in peak/rest LAVI &amp;gt;6.8 ml/m2 correlates with a higher incidence of heart failure decompensation, reduced left ventricular contractile reserve (LVCR), pulmonary congestion. We evaluate the effect of MR reparative surgery on the changes of LAVI during stress–echo. We enrolled 19 patients, 11 females and 8 males, affected by MR candidate to cardiac surgery. We performed a physical stress–echo test by using the ABCDE protocol suggested by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), before and after 12 weeks from surgery. During each test, the changes in LAVI (ΔLAVI) expressed as peak/rest difference in ml/m2 was measured. In addition, the prognostic score deriving from the sum of the ABCDE criteria was calculated, such as the LVCR (C parameter of the score) that represents a parameter of the force deriving from the hemodynamic changes during the test. In all patients we observed a significant reduction in ΔLAVI (8.4+0.5 mL/m2 vs 9.7+0.7 mL/m2; p&amp;lt;0.0001). In addition, there was a significant reduction in the ABCDE prognostic score (from 4.19+0.43 to 3.48+0.37; p=0.002), secondary to the increase in the LVCR observed approximately 3 months after surgery (from 1.77 mmHg/ml to 2.44 mmHg/ml, p&amp;lt;0.0001), as well as a significant reduction in pulmonary congestion during stress (B parameter). There were no significant changes in ejection fraction, wall motion score index–WMSI (A parameter), coronary reserve (D parameter) and heart rate reserve (E parameter). These data demonstrate for the first time that mitral valve plastic surgery is able to reduce the ΔLAVI during stress echocardiography in patients with severe MR. The surgical procedure also resulted in both an improvement in the LVCR and a reduction in the degree of pulmonary congestion, that ultimately led to an improvement in the ABCDE prognostic score.

Early source control of infection in patients seen in the emergency department: a systematic review

The term source (or focus) control encompasses all those physical measures that can be used to reduce the inoculum and modify those factors in the infectious medium that promote microbial growth or foreign antimicrobial defenses of the host. The main objective of this systematic review (SR) is to know and compare whether early detection and control of the focus (in less than 6 hours) in adult patients treated in the ED for severe infection or sepsis, compared to not controlling the focus or delayed focus control (more than 12 hours) is more effective and safer (improves clinical evolution, mortality, complications, hospital stay or need for ICU admission). A systematic review is carried out following the PRISMA regulations in the databases of PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase and ClinicalTrials.gov from January 2000 to December 31, 2023 without language restrictions and using a combination of MESH terms: "Source Control", "Early" "Infection OR Bacterial Infection OR Sepsis", "Emergencies OR Emergency OR Emergency Department" and "Adults". Observational cohort studies were included. No meta-analysis techniques were performed, but results were compared narratively. A total of 1,658 articles were identified, of which 2 that met the inclusion criteria and were classified as high quality were finally analyzed. The included studies represent a total of 2,404 patients with 678 cases in which an intervention was performed to control the focus (28.20%). In the first study, 28-day mortality was lower in patients who underwent an intervention to control the focus (12.3% vs. 22.5%; P <0.001), with an adjusted HR of 0.538 (95% CI: 0.389-0.744; P<0.001). In the second, it was demonstrated that the time elapsed from when the patient was evaluated for the first time and was hemodynamically stabilized, until the start of surgery was associated with his survival at 60 days with an OR of 0.31 (95% CI: 0.19-0.45; P <0.0001). In fact, for each hour of delay an adjusted OR of 0.29 (95% CI: 0.16-0.47; P<0.0001) is established. So if the intervention is performed before 2 hours at 60 days, 98% of the patients are still alive, if it is performed between 2-4 hours it is reduced to 78%, if it is between 4-6 hours it drops to 55%, but if it is done for more than 6 hours there will be no survivors at 60 days. This review shows that source control carried out after the evaluation of patients attending the ED reduces short-term mortality (30-60 days) and that it would be advisable to implement any required source control intervention as soon as possible, ideally early (within 6 hours).

Unusually severe neonatal presentation of mediastinal bronchogenic cyst.

Bronchogenic cysts are rare congenital malformations that occur in adults and children, with differences in distribution and presentation. We present the case of a newborn who initiated respiratory distress from the first minutes of life, presenting with hypoventilation and rightward displacement of the cardiac impulse, requiring oxygen therapy and intubation. The first radiograph shows a left pulmonary emphysema. The computerized axial tomography revealed a large mediastinal mass causing an obstructive syndrome of the left bronchus. The mass was successfully excised, resulting in a favorable clinical evolution. Although the presentation of our case is exceptional, it is worth noting that while most bronchogenic cysts are asymptomatic, they can occur in childhood, even from birth, as in our case.

Blood RNA-sequencing across the continuum of ANA-positive autoimmunity reveals insights into initiating immunopathology

ObjectiveMechanisms underpinning clinical evolution to systemic lupus erythematosus (SLE) from preceding antinuclear antibodies (ANA) positivity are poorly understood. This study aimed to understand blood immune cell transcriptional signatures associated with...

Relationship between Plasma Lipid Profile and Cognitive Status in Early Alzheimer Disease.

Alzheimer disease (AD) is a heterogeneous and complex disease in which different pathophysiological mechanisms are involved. This heterogenicity can be reflected in different atrophy patterns or clinical manifestations. Regarding biochemical pathways involved in early AD, lipid metabolism plays an important role; therefore, lipid levels have been evaluated as potential AD diagnosis biomarkers, and their levels could be related to different AD clinical manifestations. Therefore, the aim of this work is to study AD lipid profiles from early AD patients and evaluate their clinical significance. For this purpose, untargeted plasma lipidomic analysis was carried out in early AD patients (n = 31) diagnosed with cerebrospinal fluid (CSF) biomarkers. Cluster analysis was carried out to define early AD subgroups according to the lipid levels. Then, the clinical significance of each lipid profile subgroup was studied, analyzing differences for other variables (cognitive status, CSF biomarkers, medication, comorbidities, age, and gender). The cluster analysis revealed two different groups of AD patients. Cluster 1 showed higher levels of plasma lipids and better cognitive status than Cluster 2. However, no differences were found for the other variables (age, gender, medication, comorbidities, cholesterol, and triglycerides levels) between both groups. Plasma lipid levels could differentiate two early AD subgroups, which showed different cognitive statuses. However, further research with a large cohort and longitudinal study evaluating the clinical evolution of these patients is required. In general, it would involve a relevant advance in the knowledge of AD pathological mechanisms, potential treatments, and precision medicine.

Minerals and trace elements in pregnancy in women with previous bariatric surgery consequences on maternal and foetal health

BackgroundBariatric surgery (BS) may decrease the risk of these obesity-related complications; however, due to its effect on nutrient intake and absorption, it can also have adverse consequences on maternal and foetal health. The aim of this study is to describe the evolution of electrolytes and trace elements serum levels throughout pregnancy after BS, according to the surgical technique and to evaluate the effect of nutritional deficiencies on the risk of maternal-foetal complications. MethodsThis is a retrospective observational study of the clinical evolution and maternal-foetal complications in a group of women with pregnancies that occurred after BS. Clinical evolution during pregnancy, body weight, and plasma electrolytes, vitamins, and trace elements, as well as their influence on maternal-foetal outcomes were evaluated. Composite neonatal variable (CNV) was defined to evaluate unfavourable foetal outcome. Published reference values for micronutrients during pregnancy have been used. ResultsThe study includes data on 164 singleton pregnancies in 91 women. A hundred and twenty-seven pregnancies got to full term. The average birth weight was 2966 (546) g., 26.8% < P10 and 13.8% < P3 of a reference population. New-born of gestations after malabsorptive bariatric surgery had a higher risk of having a percentile of birth weight < P3. Plasma electrolytes, trace elements and vitamins throughout pregnancy showed differences depending on the surgical technique, with lower haemoglobin, ferritin, calcium, zinc, copper, vitamin A and vitamin E in the malabsorptive techniques. A high percentage of deficiency was observed, especially in the third trimester (Hb < 11 g/dl: 31.8%; ferritin < 30 mg/ml: 85.7%; zinc < 50 μg/dl: 32.4%, vitamin D < 30 ng/ml: 75.5% and < 20 ng/ml: 53.3%). A decreased plasma copper in the first trimester or zinc in the third trimester were associated with a lower percentile of new-born birth weight. A higher risk of CNV was observed in predominant malabsorptive BS and in pregnancies that had presented at least one vitamin D level lower than 20 ng/ml throughout pregnancy (30.4% vs. 7.1%, p=0.018). ConclusionsTrace elements and vitamin deficiencies are common in pregnant women after bariatric surgery, especially of iron, zinc, and vitamin D. These deficiencies might negatively affect foetal development. Further studies are needed to better define the role of micronutrients in maternal-foetal health after bariatric surgery.