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Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that frequently infiltrates the peri-kidney space ("hairy kidney" appearance), kidney pelvis and proximal ureters, leading to obstructive uropathy. Here, we analyzed the clinical characteristics, imaging findings and long-term kidney outcome of a large multicenter cohort comprising 195 consecutive patients with ECD. Retroperitoneal peri-kidney or peri-ureteral involvement was detected at diagnosis in 147 patients. Of them, 70 had hydronephrosis (bilateral in 47), and 16 with kidney atrophy (unilateral in 14). Kidney vascular peduncle infiltration was found in 60 patients, and kidney artery stenosis in 31. The estimated glomerular filtration rate (eGFR) at diagnosis was significantly lower in patients with than in those without peri-kidney involvement (median 74 vs. 98 mL/min/1.73 m

AR-1105 is a novel biodegradable sustained-release dexamethasone implant designed to deliver 6-month durability. This Phase 2 study evaluated two AR-1105 formulations with different release profiles in patients with macular edema due to retinal vein occlusion.Patients received a single intravitreal injection with 340 µg dexamethasone. In the initial phase, five patients received clinical formulation (CF) 1. In the randomized phase, 44 patients were randomized 1:1 to CF1 or CF2. The follow-up was 6 months. Patients had vision loss due to macular edema diagnosed ≥9 (central retinal vein occlusion) or ≥12 months (branch retinal vein occlusion) before screening, and could be treatment-naive or -experienced (if received prior steroids, must have demonstrated response).Both formulations improved vision and reduced retinal thickening from baseline across all visits. At Month 6, mean changes in best-corrected visual acuity were +4.3 and +8.0 letters, and mean changes in central subfield thickness were -93 µm and -211 µm in CF1 and CF2 randomized patients, respectively. Most common adverse events were reduced visual acuity, worsening macular edema, conjunctival hemorrhage, and increased intraocular pressure. No patients required surgery or laser for intraocular pressure control.Both formulations were well tolerated and demonstrated clinically meaningful and sustained improvements in vision and retinal thickening in patients with retinal vein occlusion with longstanding edema.

Introduction: Individuals with cleft palate can present with velopharyngeal dysfunction after primary palatoplasty and require a secondary treatment due to insufficiency. In these cases, the pharyngeal bulb prosthesis can be used temporarily while awaiting secondary surgery. Objective: This study aimed to investigate the outcome of treatment of hypernasality with pharyngeal bulb prosthesis in patients with history of cleft palate presenting with velopharyngeal insufficiency after primary palatal surgery. We hypothesized that the use of the pharyngeal bulb prosthesis is an effective approach to eliminate hypernasality related to velopharyngeal insufficiency in patients with cleft palate. Methods: Thirty speakers of Brazilian Portuguese (15 males and 15 females) with operated cleft palate, ages ranging from 6 to 14 years (mean: 9 years; SD = 1.87 years), participated in the study. All patients were fitted with a pharyngeal bulb prosthesis to manage velopharyngeal insufficiency while they were awaiting corrective surgery to be scheduled. Auditory-perceptual analysis of speech recorded in the conditions with and without pharyngeal bulb prosthesis were obtained from three listeners who rated the presence or absence of hypernasality for this study. Results: Seventy percent of the patients eliminated hypernasality while employing the pharyngeal bulb prosthesis, while 30% still presented with hypernasality. The comparison was statistically significant (p < 0.001). Conclusion: The use of the pharyngeal bulb prosthesis is an effective approach to eliminate hypernasality related to velopharyngeal insufficiency. Resumo Introdução: Indivíduos com fissura palatina podem apresentar disfunção velofaríngea após a palatoplastia primária e necessitam de um secundário devido à insuficiência velofaríngea. Nesses casos, o obturador faríngeo pode ser usado temporariamente enquanto se aguarda uma cirurgia secundária. Objetivo: Investigar o resultado do tratamento da hipernasalidade com o uso de obturador faríngeo em pacientes com histórico de fissura palatina que apresentam insuficiência velofaríngea após a palatoplastia primária. Nossa hipótese é que o uso do obturador faríngeo seja uma abordagem eficaz para eliminar a hipernasalidade relacionada à insuficiência velofaríngea em pacientes com fissura palatina Método: Participaram do estudo 30 indivíduos falantes do Português Brasileiro (15 homens e 15 mulheres) com fissura palatina operada, de 6 a 14 anos de idade (média: 9 anos; DP = 1,87 anos). Todos os pacientes receberam obturador faríngeo para o tratamento da insuficiência velofaríngea, enquanto aguardavam vaga para a cirurgia secundária. A análise perceptivo-auditiva da fala, realizada nas condições com e sem obturador faríngeo, foi realizada por três ouvintes, quanto à presença e ausência da hipernasalidade. Resultados: 70% dos pacientes eliminaram a hipernasalidade de fala com o uso do obturador faríngeo, enquanto 30% não eliminaram. A comparação foi estatisticamente significante (p < 0,001). Conclusão: O uso temporário do obturador faríngeo é uma abordagem efetiva para eliminar a hipernasalidade decorrente da insuficiência velofaríngea.

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren’s syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies., Currò et al. investigate the prevalence of RFC1 expansions in a cohort of patients with chronic idiopathic axonal polyneuropathy. RFC1 expansions were found in 34% of patients with sensory neuropathy, but in none with sensory-motor neuropathy. Clinical features and diagnostic clues that should lead to suspicion of RFC1 neuropathy are discussed.

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

Supracondylar humeral fractures account for 60% of elbow fractures in childhood, with cubitus varus being its most common complication. It can be avoided by accurate assessment of distal humeral alignment after fracture reduction, and the Baumann angle is the usual measurement for this purpose. However, several reports demonstrate an inconsistency of this angle, and our hypothesis is that reliability could be improved with angles drawn between the trochlear physeal line and the humeral longitudinal axis. The aim of the study was to compare intra- and interobserver reliability between the Baumann angle and angles drawn between the trochlear physeal line and (1) humeral longitudinal axis (X-angle), (2) humeral lateral cortex line (Y-angle), (3) humeral medial cortex line (Z-angle). Angle measurements were performed on 141 distal humerus' radiographs of children aged 3-10 years by five observers in a tertiary hospital. The measurements were compared for their intra- and interobserver agreement. All measurements showed good or excellent intraobserver agreement levels, with the highest for Z-angle [intraclass correlation coefficient (ICC) = 0.906] and the lowest for Baumann angle. There were also excellent interobserver agreement levels for all angles, the highest for Z-angle (ICC = 0.885). There are indications that Z-angle had higher agreement levels when compared to the others (ICC = 0.954; 0.936-0.969) in the group aged 7-10 years. The angle drawn between the humeral medial cortex and trochlear physeal line showed greater agreement than the other angles analysed, becoming a potentially useful tool for evaluation of children with supracondylar humeral fractures in daily practice.

Background: Laparoscopic adrenalectomy (LA) is considered the "gold standard" treatment of adrenal lesions that are often coincidentally diagnosed during the radiologic workup of other diseases. This study aims to evaluate the intraoperative role of indocyanine green (ICG) fluorescence associated with preoperative 3-dimensional reconstruction (3DR) in laparoscopic adrenalectomy in terms of perioperative outcomes. To our knowledge, this is the first prospective case-controlled report comparing these techniques. Materials and Methods: All consecutive patients aged≥18 and undergoing laparoscopic transperitoneal adrenalectomy for all adrenal masses from January 1, 2019 to January 31, 2022 were prospectively enrolled. Patients undertaking standard LA and those undergoing preoperative 3D reconstruction and intraoperative ICG fluorescence were matched through a one-on-one propensity score matching analysis (PSM) for age, gender, BMI, CCI score, ASA score, lesion histology, tumor side, and lesion diameter. Differences in operative time, blood loss, intraoperative and postoperative complications, conversion rate, and length of stay were analyzed. Results: After propensity score matching analysis, we obtained a cohort of 36 patients divided into 2 groups of 18 patients each. The operative time and intraoperative blood loss were shorter in patients of the 3DR group (P=0,004 and P=0,004, respectively). There was no difference in terms of length of stay, conversion rate, and intraoperative and postoperative complications between the 2 groups. Conclusions: The use of intraoperative ICG in LA and preoperative planning with 3DR images is a safe and useful addition to surgery. Furthermore, we observed a reduction in terms of operating time and intraoperative blood loss.

BACKGROUND Portal vein resection and reconstruction in locally advanced pancreatic cancer represents a potentially curative treatment in selected patients without increasing surgical mortality. However, vascular reconstruction after segmental venous resection is challenging. The parietal peritoneum has emerged as a venous substitute but few reports include its use as a tubular graft. We report a retrospective series of portal vein reconstruction using a falciform ligament tubular graft during pancreaticoduodenectomy. MATERIAL AND METHODS Technical aspects and short-term morbidity and mortality after pancreaticoduodenectomy with falciform ligament tubular graft interposition were analyzed. RESULTS Among 21 patients who used parietal peritoneum for venous substitution between 2015 and 2019, eight underwent pancreaticoduodenectomy with venous resection and reconstruction using interposition of falciform ligament tubular graft. The mean duration of surgery and clamping time were 350 and 27 min, respectively. No perioperative blood transfusion was required. All the grafts were patent the day after surgery. No complication related to venous obstruction was detected during the hospital stay. Two patients had postoperative pancreatic fistula. No further intervention was needed. The 90-day mortality was null. CONCLUSIONS The use of interposition of falciform ligament tubular graft for portal venous reconstruction during pancreaticoduodenectomy seems to be a reliable, inexpensive, and safe procedure.

Injuries with exposure of soft tissue are frequent in orthopaedics. Innovative therapies using prosthesis as an auxiliary material to treat this type of injury are under development, aiming to overcome applicability and execution limitations of myocutaneous flap techniques. Figueiredo’s technique uses a polypropylene prosthesis extracted from sterile saline to treat trauma at the fingertip. It is an alternative technique with a high success rate, reproducible, low cost and easy to apply. This article reports a case of foot injury with exposure of soft tissue treated with a treatment similar to Figueiredo’s technique. The patient was admitted with a large and contaminated skin wound, muscle damage, tendon exposure, cuboid fracture and bone loss. Initially, debridement was performed. After 72 hours, a polypropylene prosthesis extracted from a sterile saline bottle was implanted and subsequently replaced after 60 days. After 76 days, the prosthesis was removed. There was no infection. 8 months later, there was total healing by second intention. The patient's motor and sensory functions were preserved. This case study shows that Figueiredo’s technique can also be employed in more extensive injuries, representing an alternative to using myocutaneous flaps. The polypropylene prosthesis is extremely affordable, which enables resolution of cases in a greater number of services. This technique still offers the best aesthetic result and does not compromise other body regions.

Cholangiography with indocyanine green fluorescence (ICG) is increasingly used to visualize the bile duct anatomy during laparoscopic cholecystectomy. Biliary leaks are rare complications after laparoscopic cholecystectomy, result could be lethal. Lesion's site is not always visible. We present an interesting case of a patient with biloma due to an iatrogenic lesion of the biliary tract, treated in urgency using ICG fluorescence. To our knowledge, this is the only case in the literature.A 62-years-old patient after 7 days from laparoscopic cholecystectomy presented abdominal pain and fever. Blood tests showed an increase of inflammation indexes. Abdominal US and abdominal CT revealed a conspicuous right sub-hepatic fluid. We performed a laparoscopy using ICG fluorescence to find the biliary leak. Operative time of surgery was 60 min. There were no complications during this procedure.ICG is a safe and effective procedure that enables real-time visualization of the biliary system. In some cases, it can also be used in urgent surgery, where the biliary anatomy is much more complex.Biloma, Indocyanine green fluorescence, Iatrogenic biliary leaks, Urgent surgery.Le lesioni iatrogene delle vie biliari rappresentano una rara ma temibile complicanza della colecistectomia laparoscopica. In questo lavoro, presentato durante il 39° congresso nazionale ACOI e selezionato per un premio, riportiamo il caso di un paziente con un voluminoso biloma insorto dopo colecistectomia laparoscopica, trattato chirurgicamente con l’ausilio del verde di indocianina. Il paziente si presentava presso la nostra struttura sette giorni dall’intervento con nausea, dolore addominale e febbre. L’ecografia e la TC addominali mostravano una voluminosa raccolta in loggia colecistica. Durante una laparoscopia esplorativa eseguita in urgenza, il leak sul letto epatico è stato evidenziato e riparato dopo la somministrazione del verde di indocianina. Il decorso postoperatorio è stato regolare e il paziente dimesso in decima giornata. In conclusione, l’ICG, già utilizzato in chirurgia epatica per prevenire e identificare lesioni biliari, potrebbe costituire un valido supporto anche nella gestione di tali complicanze insorte tardivamente post-colecistectomia.

The application of the minimally invasive approach has shown to be safe and effective for liver surgery and is in constant growth. The indications for laparoscopic surgery are steadily increasing across the field. In the early 2000s, robotic surgery led to some additional improvements, such as tremor filtration, instrument stability, 3D view and more comfort for the surgeon. These techniques bring in some advantages compared to the traditional OLR: less blood loss, shorter admissions, fewer adhesions, and a faster postoperative recovery and better outcomes in case of further hepatectomy for tumor recurrence has been shown. Concerning which is the best minimally invasive approach between laparoscopic and robotic surgery, the evidence is still conflicting. The latter shows good potential, since the endo-wristed instruments work similarly to the surgeon's hands, even with an intact abdominal wall. However, the technique is still under development, burdened by important costs, and limited by the lack of some instruments available for the laparoscopic approach. The paucity of universally accepted and proven data, especially concerning long-term outcomes, hampers drawing univocal acceptance at present. Furthermore, the number of variables related both to the patient and the disease further complicates the decision leading to a treatment tailored to each patient with strict selection. This review aims to explore the main differences between laparoscopic and robotic surgery, focusing on indications, operative technique and current debated clinical issues in recent literature.

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Radiographic skeletal survey (R-SS) is the standard imaging technique for the initial staging of Langerhans cell histiocytosis (LCH). Whole-body magnetic resonance imaging (WB-MRI) has been proposed as an effective, radiation-free alternative.We prospectively assessed patients with LCH followed at three tertiary centers in Italy and Austria. Two national study protocols were independently designed, and data were then pooled to increase the power of their findings. R-SS and WB-MRI were performed at diagnosis and repeated at the follow-up to confirm the nature of the identified lesions and to study their evolution.Data from 67 patients were analyzed (52 from Italy and 15 from Austria). Compared to R-SS, WB-MRI identified 29 additional skeletal lesions in 14 patients (including two false-positive lesions). Two skeletal lesions were detected at R-SS and missed at WB-MRI (false negative). Per-lesion sensitivity rates were 78.6% (95% CI: 71.0-85.9) for R-SS and 98.4% (95% CI: 94.4-99.8) for WB-MRI, respectively. Based on WB-MRI findings, six patients would have been upstaged to a higher risk class than staging with R-SS.WB-MRI had a significantly higher detection rate for skeletal lesions compared to R-SS. Clinical and radiology expertise is required to avoid upstaging and overtreatment.

[Background]: Water T2 (T2H2O ) mapping is increasingly being used in muscular dystrophies to assess active muscle damage. It has been suggested as a surrogate outcome measure for clinical trials. Here, we investigated the prognostic utility of T2H2O to identify changes in muscle function over time in limb girdle muscular dystrophies., [Methods]: Patients with genetically confirmed dysferlinopathy were assessed as part of the Jain Foundation Clinical Outcomes Study in dysferlinopathy. The cohort included 18 patients from two sites, both equipped with 3-tesla magnetic resonance imaging (MRI) systems from the same vendor. T2H2O value was defined as higher or lower than the median in each muscle bilaterally. The degree of deterioration on four functional tests over 3 years was assessed in a linear model against covariates of high or low T2H2O at baseline, age, disease duration, and baseline function., [Results]: A higher T2H2O at baseline significantly correlated with a greater decline on functional tests in 21 out of 35 muscles and was never associated with slower decline. Higher baseline T2H2O in adductor magnus, vastus intermedius, vastus lateralis, and vastus medialis were the most sensitive, being associated bilaterally with greater decline in multiple timed tests. Patients with a higher than median baseline T2H2O (>40.6 ms) in the right vastus medialis deteriorated 11 points more on the North Star Ambulatory Assessment for Dysferlinopathy and lost an additional 86 m on the 6-min walk than those with a lower T2H2O (, [Conclusions]: In dysferlinopathy, T2H2O did not correlate with current functional ability. However, T2H2O at baseline was higher in patients who worsened more rapidly on functional tests. This suggests that inter-patient differences in functional decline over time may be, in part, explained by different severities of the active muscle damage, assessed by T2H2O measure at baseline. Significant challenges remain in standardizing T2H2O values across sites to allow determining globally applicable thresholds. The results from the present work are encouraging and suggest that T2H2O could be used to improve prognostication, patient selection, and disease modelling for clinical trials., The Jain COS consortium would like to thank the study participants and their families for their invaluable contribution and would also like to acknowledge the ongoing support the Jain Foundation provides in the development, management, and analysis of this study. The Jain Foundation, based in Seattle, USA, is entirely focused on LGMD2B/dysferlinopathy/Miyoshi myopathy. The foundation does not solicit funding from patients but instead funds research and clinical studies worldwide with the goal of finding treatments for dysferlinopathy.

Colorectal cancer (CRC) is the third most common malignancy worldwide, with approximately 50% of patients developing colorectal cancer liver metastasis (CRLM) during the follow-up period. Management of CRLM is best achieved via a multidisciplinary approach and the diagnostic and therapeutic decision-making process is complex. In order to optimize patients’ survival and quality of life, there are several unsolved challenges which must be overcome. These primarily include a timely diagnosis and the identification of reliable prognostic factors. Furthermore, to allow optimal treatment options, a precision-medicine, personalized approach is required. The widespread digitalization of healthcare generates a vast amount of data and together with accessible high-performance computing, artificial intelligence (AI) technologies can be applied. By increasing diagnostic accuracy, reducing timings and costs, the application of AI could help mitigate the current shortcomings in CRLM management. In this review we explore the available evidence of the possible role of AI in all phases of the CRLM natural history. Radiomics analysis and convolutional neural networks (CNN) which combine computed tomography (CT) images with clinical data have been developed to predict CRLM development in CRC patients. AI models have also proven themselves to perform similarly or better than expert radiologists in detecting CRLM on CT and magnetic resonance scans or identifying them from the noninvasive analysis of patients’ exhaled air. The application of AI and machine learning (ML) in diagnosing CRLM has also been extended to histopathological examination in order to rapidly and accurately identify CRLM tissue and its different histopathological growth patterns. ML and CNN have shown good accuracy in predicting response to chemotherapy, early local tumor progression after ablation treatment, and patient survival after surgical treatment or chemotherapy. Despite the initial enthusiasm and the accumulating evidence, AI technologies’ role in healthcare and CRLM management is not yet fully established. Its limitations mainly concern safety and the lack of regulation and ethical considerations. AI is unlikely to fully replace any human role but could be actively integrated to facilitate physicians in their everyday practice. Moving towards a personalized and evidence-based patient approach and management, further larger, prospective and rigorous studies evaluating AI technologies in patients at risk or affected by CRLM are needed.

Mutations in the RYR1 gene, encoding ryanodine receptor 1 (RyR1), are a well-known cause of Central Core Disease (CCD) and Multi-minicore Disease (MmD). We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for RYR1 mutation. At least one RYR1 mutation was identified in 69 of them and these patients were further studied. Clinical and histopathological features were collected. Clinical phenotype was highly heterogeneous ranging from asymptomatic or paucisymptomatic hyperCKemia to severe muscle weakness and skeletal deformity with loss of ambulation. Sixty-eight RYR1 mutations, generally missense, were identified, of which 16 were novel. The combined analysis of the clinical presentation, disease progression and the structural bioinformatic analyses of RYR1 allowed to associate some phenotypes to mutations in specific domains. In addition, this study highlighted the structural bioinformatics potential in the prediction of the pathogenicity of RYR1 mutations. Further improvement in the comprehension of genotype–phenotype relationship of core myopathies can be expected in the next future: the actual lack of the human RyR1 crystal structure paired with the presence of large intrinsically disordered regions in RyR1, and the frequent presence of more than one RYR1 mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect.

Personalized medicine is the future of medical practice. In oncology, tumor heterogeneity assessment represents a pivotal step for effective treatment planning and prognosis prediction. Despite new procedures for DNA sequencing and analysis, non-invasive methods for tumor characterization are needed to impact on daily routine. On purpose, imaging texture analysis is rapidly scaling, holding the promise to surrogate histopathological assessment of tumor lesions. In this work, we propose a tree-based representation strategy for describing intra-tumor heterogeneity of patients affected by metastatic cancer. We leverage radiomics information extracted from PET/CT imaging and we provide an exhaustive and easily readable summary of the disease spreading. We exploit this novel patient representation to perform cancer subtyping according to hierarchical clustering technique. To this purpose, a new heterogeneity-based distance between trees is defined and applied to a case study of prostate cancer. Clusters interpretation is explored in terms of concordance with severity status, tumor burden and biological characteristics. Results are promising, as the proposed method outperforms current literature approaches. Ultimately, the proposed method draws a general analysis framework that would allow to extract knowledge from daily acquired imaging data of patients and provide insights for effective treatment planning.

Peripherin (PRPH), a type III intermediate filament, assembles with neurofilaments in neurons of the peripheral nervous system, including lower motor neurons (LMN). To evaluate the role of PRPH in LMN degeneration, we assessed PRPH and neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and serum of 91 patients with motor neuron diseases (MND) and 69 controls. Overall, we found PRPH to be more concentrated in serum than in CSF. Serum PRPH resulted significantly increased in MND patients but it was unrelated to CSF‐NfL or survival in the amyotrophic lateral sclerosis (ALS) subset. PRPH might represent a marker of LMN involvement.

Resection of the inferior vena cava may be required in the courses of oncological surgeries for the tumors originating from or invading it. Management of the remaining defect depends on the extension of the resection. Partial or complete replacement of the inferior vena cava, with a patch or interposition graft, may be required. Standard techniques for the reconstruction with a prosthetic material or the autologous veins can be associated with the prosthetic graft infection, high cost, long-standing anticoagulation, technical difficulties, and/or need for extra incisions. The use of the autologous peritoneum represents an easy and inexpensive alternative for the partial and complete inferior vena cava reconstructions.

To investigate the association of oral health condition with the occurrence of medication-related osteonecrosis of the jaw (MRONJ) in a cancer population. A multicenter cross-sectional study was conducted with cancer patients exposed to bisphosphonates for at least 7 months. Dental and periodontal conditions were assessed by epidemiological indices. The sample consisted of 80 patients under bisphosphonate therapy, nine of which were allocated to group 1 (with MRONJ) and 71 to group 2 (without MRONJ). Osteonecrosis cases presented 19 decayed, missing, and filled teeth on average. Moderate gingival inflammation was noted in both groups and together with severe inflammation exceeded 50% of the groups. The presence of dental calculus was detected in about half of the individuals in both groups. Shallow periodontal pockets were detected in about 25% of both groups. Deep periodontal pockets were more prevalent among patients with osteonecrosis. Regular oral hygiene was detected in approximately 25% of individuals in both groups. There was a strong positive correlation between the clinical staging of osteonecrosis and decayed, missing, and filled teeth index (DMFTI). Patients had a poor oral health condition. All but one osteonecrosis case had no previous history of tooth extraction; oral infections seemed to play a major role in the development of bone necrosis. Advanced osteonecrosis stages were associated with a higher DMFTI.

Background Circulating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC). Materials and Methods We designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression. Results One hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p = .002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16–3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p = .003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95–2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five. Conclusion We provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC. Implications for Practice This prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.

The aim of the present systematic review is to examine the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) associated with computed tomography (CT) or magnetic resonance imaging (MRI) in assessing response to preoperative chemotherapy or chemoradiotherapy (CRT) for patients with borderline and resectable pancreatic ductal adenocarcinoma (PDAC). Three researchers ran a database query in PubMed, Web of Science and EMBASE. The total number of patients considered was 488. The most often used parameters of response to therapy were the reductions in the maximum standardized uptake value (SUVmax) or the peak standardized uptake lean mass (SULpeak). Patients whose SUVs were higher at the baseline (before CRT) were associated with a better response to therapy and a better overall survival. SUVs remaining high after neoadjuvant therapy correlated with a poor prognosis. Available data indicate that FDG PET/CT or PET/MRI can be useful for predicting and assessing response to CRT in patients with resectable or borderline PDAC.

Wide area surveillance has become of critical importance, particularly for border control between countries where vast forested land border areas are to be monitored. In this paper, we address the problem of the automatic detection of activity in forbidden areas, namely forested land border areas. In order to avoid false detections, often triggered in dense vegetation with single sensors such as radar, we present a multi sensor fusion and tracking system using passive infrared detectors in combination with automatic person detection from thermal and visual video camera images. The approach combines weighted maps with a rule engine that associates data from multiple weighted maps. The proposed approach is tested on real data collected by the EU FOLDOUT project in a location representative of a range of forested EU borders. The results show that the proposed approach can eliminate single sensor false detections and enhance accuracy by up to 50%.

Clinically describing hypertensive patients initiating nebivolol/zofenopril extemporaneous combination (NZ-EXC) and estimating the number of patients currently receiving NZ-EXC and of those potentially eligible for the fixed-dose combination of the two molecules (NZ-FDC) in Italy. This retrospective observational study used data from IQVIA Italian Longitudinal Patient Database (LPD). Adult hypertensive patients firstly prescribed NZ-EXC between 1 July 2011 and 30 June 2020 were identified and their demographic and clinical characteristics were extracted. Treatment adherence was evaluated as proportion of days covered (PDC) and classified as low (PDC

Tumor growth and metastatic spreading are heavily affected by the P2X7 receptor as well as microvesicles and exosomes release into the tumor microenvironment. P2X7 receptor stimulation is known to trigger vesicular release from immune and central nervous system cells. However, P2X7 role in microvesicles and exosomes delivery from tumor cells was never analyzed in depth. Here we show that P2X7 is overexpressed in patients affected by metastatic malignant melanoma and that its expression closely correlates with reduced overall survival. Antagonism of melanoma cell-expressed P2X7 receptor inhibited in vitro anchorage-independent growth and migration and in vivo dissemination and lung metastasis formation. P2X7 stimulation triggered the release of miRNA-containing microvesicles and exosomes from melanoma cells, profoundly altering the nature of their miRNA content, as well as their dimensions and quantity. Among the more than 200 miRNAs that we found up-or-down-modulated for each vesicular fraction tested, we identified three miRNAs, miR-495-3p, miR-376c-3p, and miR-6730-3p, that were enriched in both the exosome and microvesicle fraction in a P2X7-dependent fashion. Interestingly, upon transfection, these miRNAs promoted melanoma cell growth or migration, and their vesicular release was minimized by P2X7 antagonism. Our data unveil an exosome/microvesicle and miRNA-dependent mechanism for the pro-metastatic activity of the P2X7 receptor and highlight this receptor as a suitable prognostic biomarker and therapeutic target in malignant melanoma.

Recent scientific evidence suggests a link between migraine and brain energy metabolism. In fact, migraine is frequently observed in mitochondrial disorders. We studied 46 patients affected by mitochondrial disorders, through a headache-focused semi-structured interview, to evaluate the prevalence of migraine among patients affected by mitochondrial disorders, the possible correlations between migraine and neuromuscular genotype or phenotype, comorbidities, lactate acid levels and brain magnetic resonance spectroscopy. We explored migraine-related disability, analgesic and prophylactic treatments. Diagnoses were achieved according to International Classification of Headache Disorders, 3rd edition. Lifetime prevalence of migraine was 61% (28/46), with high values in both sexes (68% in females, 52% in males) and higher than the values found in both the general population and previous literature. A maternal inheritance pattern was reported in 57% of cases. MIDAS and HIT6 scores revealed a mild migraine-related disability. The high prevalence of migraine across different neuromuscular phenotypes and genotypes suggests that migraine itself may be a common clinical manifestation of brain energy dysfunction. Our results provide new relevant indications in favour of migraine as the result of brain energy unbalance.

Non-dystrophic myotonias and periodic paralyses are a heterogeneous group of disabling diseases classified as skeletal muscle channelopathies. Their genetic characterization is essential for prognostic and therapeutic purposes; however, several genes are involved. Sanger-based sequencing of a single gene is time-consuming, often expensive; thus, we designed a next-generation sequencing panel of 56 putative candidate genes for skeletal muscle channelopathies, codifying for proteins involved in excitability, excitation-contraction coupling, and metabolism of muscle fibres. We analyzed a large cohort of 109 Italian patients with a suspect of NDM or PP by next-generation sequencing. We identified 24 patients mutated in CLCN1 gene, 15 in SCN4A, 3 in both CLCN1 and SCN4A, 1 in ATP2A1, 1 in KCNA1 and 1 in CASQ1. Eight were novel mutations: p.G395Cfs*32, p.L843P, p.V829M, p.E258E and c.1471+4delTCAAGAC in CLCN1, p.K1302R in SCN4A, p.L208P in ATP2A1 and c.280–1G>C in CASQ1 genes. This study demonstrated the utility of targeted next generation sequencing approach in molecular diagnosis of skeletal muscle channelopathies and the importance of the collaboration between clinicians and molecular geneticists and additional methods for unclear variants to make a conclusive diagnosis.

International audience; Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF β2) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF β2 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss Muscular Dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF β2-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF β2 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF β2-dependent mechanisms were also determined in laminopathic cells, where TGF β2 activated AKT/mTOR phosphorylation. These data show that TGF β2 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF β2 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies.

An abnormal structural form of glycogen (with less branching points or amylopectin-like polysaccharide) called polyglucosan (PG) may accumulate in various tissues such as striated and smooth muscles, brain, nerve, liver and skin, and cause a group of nine different genetic disorders manifesting with a variety of clinical phenotypes that affect mainly the nervous system (Lafora disease, adult PG body disease), the heart (glycogen storage disease type XV, hypertrophic cardiomyopathy type 6, PG body myopathy type 1) and the skeletal muscle (glycogen storage disease type IV, glycogen storage disease type VII, PG body myopathy type 2), depending on the organs which are mostly affected by the PG aggregates. The pathological feature of PG storage in tissues is a hallmark of these disorders. Whole-genome sequencing has allowed to obtain a diagnosis in a large number of patients with a previously unrecognized disorder. We describe the clinical, pathological and molecular features of these genetic disorders, for many of which the pathological mechanisms underlying the corresponding mutant gene have been investigated and, at least in part, understood.

Results of three rapid immunochromatographic tests (ICTs) were compared with those obtained with two automated immunoassays for evaluation of their usefulness. One hundred fifty-nine patients and 67 healthy volunteers were included. Different assays demonstrate 41-45% of diagnostic sensitivities and 91-98% of specificities, with substantial agreement (89.3-91.2%), but a high percentage of weak positive results (13-22%) was observed with ICTs. ICTs performances were comparable to those of automated immunoassays. ICTs could have a role as screening approach due to their easy usability. Subjective interpretation, significant rate of uncertain results, uncertainty on viral antigens source are undoubtedly drawbacks.

A retrospective analysis of a comprehensive series of high-volume air samples (n = 70) collected during 2010-2011 in Toronto (Canada) was performed. Seven UV compounds were analyzed by gas chromatography-tandem mass spectrometry (GC-MS/MS) with sum of concentrations (gas + particle phase) ranging from 80 to 2030 pg/m3. Homosalate (HMS) was the most prevalent organic UV-filter in air (47% of the total concentration), followed by 2-ethylhexyl salicylate (EHS, ∼29%), E- and Z-2-ethylhexyl 4-methoxycinnamate (EHMC, ∼17%). Ambient air (gas + particle phase) concentrations of organic UV-filters showed a strong seasonality, with peak levels during the summer. An analysis of Clausius-Clapeyron slopes indicated that much of the ambient burden of organic UV-filters are explained by volatilization from terrestrial and aquatic surfaces and supplemented with human activities and use of lotions and sunscreens, containing organic UV-filters, in addition to its use in plastics, textiles, paints, and pesticides. The results showed that organic UV-filters exist mainly in the gas phase with some exceptions, for instance, octocrylene (OCR), which was associated with both gas and particle phases, and avobenzone (AVB), which was predominantly in the particle phase. Lastly, this study revealed the need for basic physical chemical property data for organic UV-filters, including information on transformation rates and products, for better evaluating their environmental fate and effects. Fil: Pegoraro, César Nicolás. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentina Fil: Harner, Tom. Environment And Climate Change Canada; Canadá Fil: Su, Ky. Environment And Climate Change Canada; Canadá Fil: Ahrens, Lutz. Swedish University Of Agricultural Sciences; Suecia

Micronutrient deficiency affects billions of people, especially in countries where the diet is low in diversity with inadequate consumption of fruits, vegetables, and animal-source foods, and higher consumption of staple food, i.e., cereals, that have low concentrations of micronutrients. Genetic biofortification is a strategy to mitigate this problem and ensure nutritional security. Wheat is a target of genetic biofortification since it contributes significantly to the caloric requirement. The biofortification process involves a screening related to the presence of genetic variability for grain mineral content. Also, the accumulation of toxic elements must be considered to ensure food safety, because if ingested above the allowed concentrations, it represents health risks. In this sense, this study aimed to quantify the micronutrients iron, zinc, copper, selenium, and manganese and toxic elements arsenic and cadmium in a Brazilian wheat panel grown in Southern Brazil. The presence of genetic variability for the accumulation of micronutrients in the grain was detected; however, we observed that only the copper and manganese accumulation meet the human daily requirements. Iron, zinc, and selenium were detected in insufficient concentration to meet the daily demand. Arsenic and cadmium accumulation were not detected in wheat grain. The wheat genotypes grown in Brazil displayed a similar profile to that found in other countries which may be due to common high-yield breeding goals and the narrowing of the genetic variability, observed worldwide. Thus, the wheat genetic biofortification success in Brazil depends on the introduction of foreign genotypes, landraces, and wild relatives.

LGMD D2 is a disease caused by TNPO3 mutation. We describe the expression of TNPO3 and selected proteins, likely modified by TNPO3 mutation, in muscle biopsies of affected patients. We also aim to find other genes involved in pathways correlated to TNPO3. Our morphological study on LGMD D2 muscle described the expression of TNPO3 and SRSF1, a splicing factor transported by TNPO3. Moreover, we investigated some sarcomeric and nuclear proteins, likely altered by TNPO3 mutation. Through an in silico approach we tried to identify genes involved in pathways that include, besides TNPO3 and SRSF1, p62 and Murf-1, altered in LGMD D2. In patients' muscles TNPO3 appeared weaker and randomly organized, with sporadic cytoplasmic aggregates positive for TNPO3; both SRSF1 and sarcomeric alpha actinin showed a different expression, while there were no alterations in the expression of the nuclear proteins. The in silico study lead to identify five genes, all coding for proteins responsible for muscle contraction. Our data suggest a possible interference in the morphology and function of myofibrillar network by mutated TNPO3; these findings are supported by the in silico identification of genes involved in muscle contraction that could help to explain the pathogenic mechanisms of LGMD D2.

Background Serial assessment of phosphorus is currently recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, but its additional value versus a single measurement is uncertain. Methods We studied data from 17 414 HD patients in the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study, and calculated the area under the curve (AUC) by multiplying the time spent with serum phosphorus >4.5 mg/dL over a 6-month run-in period by the extent to which this threshold was exceeded. We estimated the association between the monthly average AUC and cardiovascular (CV) mortality using Cox regression. We formally assessed whether AUC was a better predictor of CV mortality than other measures of phosphorus control according to the Akaike information criterion. Results Compared with the reference group of AUC = 0, the adjusted hazard ratio (HR) of CV mortality was 1.12 [95% confidence interval (CI) 0.90–1.40] for AUC > 0–0.5, 1.26 (95% CI 0.99–1.62) for AUC > 0.5–1, 1.44 (95% CI 1.11–1.86) for AUC > 1–2 and 2.03 (95% CI 1.53–2.69) for AUC > 2. The AUC was predictive of CV mortality within strata of the most recent phosphorus level and had a better model fit than other serial measures of phosphorus control (mean phosphorus, months out of target). Conclusions We conclude that worse phosphorus control over a 6-month period was strongly associated with CV mortality. The more phosphorus values do not exceed 4.5 mg/dL the better is survival. Phosphorus AUC is a better predictor of CV death than the single most recent phosphorus level, supporting with real-world data KDIGO’s recommendation of serial assessment of phosphorus to guide clinical decisions.

International audience; Congenital titinopathies are myopathies with variable phenotypes and inheritance modes. Here, we fully characterized, using an integrated approach (deep phenotyping, muscle morphology, mRNA and protein evaluation in muscle biopsies), two siblings with congenital multicore myopathy harboring three TTN variants predicted to affect titin stability and titin-myosin interactions. Muscle biopsies showed multicores, type 1 fiber uniformity and sarcomeric structure disruption with some thick filament loss. Immunohistochemistry and Western blotting revealed a marked reduction of fast myosin heavy chain iso-forms. This is the first observation of a titinopathy suggesting that titin defect leads to secondary loss of fast myosin heavy chain isoforms.

Measurement of gene expression at the single-cell level has led to important advances in the study of transcriptional regulation programs in healthy and disease states. In particular, single-cell gene expression approaches have shed light on the high level of transcriptional heterogeneity of individual cells, both at baseline and in response to experimental or environmental perturbations. We have developed a method for High-Content Imaging (HCI)-based quantification of transcript abundance at the single-cell level in primary human immune cells and have validated its performance under multiple experimental conditions to demonstrate its general applicability. This method, which we abbreviate as hcHCR, combines the high sensitivity of the hybridization chain reaction (HCR) for the visualization of mRNA molecules in single cells, with the speed, scalability, and technical reproducibility of HCI. We first tested eight microscopy-compatible attachment substrates for short-term culture of primary human B cells, T cells, monocytes, or neutrophils. We then miniaturized HCR in a 384-well format and documented the ability of the method to detect increased or decreased transcript abundance at the single-cell level in thousands of cells for each experimental condition by HCI. Furthermore, we demonstrated the feasibility of multiplexing gene expression measurements by simultaneously assaying the abundance of two transcripts per cell, both at baseline and in response to an experimental stimulus. Finally, we tested the robustness of the assay to technical and biological variation. We anticipate that hcHCR will be a suitable and cost-effective assay for low- to medium-throughput chemical, genetic or functional genomic screens in primary human cells, with the possibility of performing personalized screens or screens on cells obtained from patients with a specific disease.

Funder: Howard Hughes Medical Institute, Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with a severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD) but of much earlier onset, caused by heterozygous frameshift variants in the RBP hnRNPA2/B1. All disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and are translated to produce hnRNPA2/B1 protein with the same neomorphic C-terminal sequence. In contrast to previously reported disease-causing missense variants in HNRNPA2B1, these frameshift variants do not increase the propensity of hnRNPA2 protein to fibrillize. Rather, the frameshift variants have reduced affinity for the nuclear import receptor karyopherin β2, resulting in cytoplasmic accumulation of hnRNPA2 protein in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with HNRNPA2B1 to include an early-onset form of OPMD caused by frameshift variants that alter its nucleocytoplasmic transport dynamics.

Introduction: the follow-up of small for gestational age (SGA) preterm infants is critical due to their differentiated postnatal growth pattern. Objective: to investigate the weight z-score behavior in SGA preterm infants during a four-week stay in a Neonatal Intensive Care Unit. Methods: a retrospective longitudinal study with data from nutritional anamneses of 190 preterm infants admitted to a Neonatal Intensive Care Unit between January/2017 and December/2019, classified according to nutritional status at birth as either SGA or appropriate for gestational age (AGA). Linear regression was used to verify association between weight z-score with gestational age, birth weight, initiation of enteral nutrition and relative amount of energy and protein administered. Results: SGA preterm infants accounted for 23 % of the study participants. In SGA, the difference in weight score was observed at week 1 when compared to admission (p0.05), while in AGA there was a difference sustained during the whole period (p0.05). In SGA, the linear regression analysis showed that the change in z-score was explained by time to start of enteral nutrition (p = 0.033), gestational age (p = 0.003) and birth weight (p = 0.001). In AGA the change was explained by gestational age (p = 0.000) and birth weight (p = 0.000). Conclusion: the weight z-score behavior in preterm infants was downward compared to admission, stable at the end of 4 weeks, and different according to nutritional status at birth. In the AGA group the decline in nutritional status was not recovered throughout hospitalization and in the SGA group the unfavorable nutritional status was maintained.Introducción: el seguimiento de los prematuros pequeños para la edad gestacional (PEG) es crítico debido al patrón de crecimiento posnatal diferenciado. Objetivo: investigar el comportamiento de la puntuación z del peso en recién nacidos prematuros PEG durante cuatro semanas de estancia en una unidad de cuidados intensivos neonatales. Métodos: estudio longitudinal retrospectivo con datos de anamnesis nutricionales de 190 prematuros ingresados en una unidad de cuidados intensivos neonatales entre enero/2017 y diciembre/2019, clasificados según el estado nutricional al nacer como PEG o como adecuado para la edad gestacional (AEG). Se utilizó la regresión lineal para verificar la asociación entre la puntuación z del peso con la edad gestacional, el peso al nacer, el inicio de la nutrición enteral y la cantidad relativa de energía y proteínas administradas. Resultados: los bebés prematuros PEG representaron el 23 % de los participantes en el estudio. En el grupo PEG, la diferencia de la puntuación z del peso se observó en la semana 1 en comparación con el ingreso (p0,05), mientras que en el grupo AEG hubo diferencia durante todo el período evaluado (p0,05). En los PEG, el análisis de regresión lineal mostró que el cambio de la puntuación z se explicaba por el tiempo transcurrido hasta el inicio de la nutrición enteral (p = 0,033), la edad gestacional (p = 0,003) y el peso al nacer (p = 0,001). En el caso de la AEG, el cambio se explicaba por la edad gestacional (p = 0,000) y el peso al nacer (p = 0,000). Conclusión: el comportamiento de la puntuación z del peso en los prematuros fue descendente en comparación con la admisión, estable al final de 4 semanas y diferente según el estado nutricional al nacer. En el caso de los AEG, el estado nutricional no se recuperó a lo largo de la investigación y, en el caso de los PEG, el estado nutricional desfavorable se mantuvo.