Nail patella syndrome: a rare cause of renal failure in a young adult

Nail Patella Syndrome (NPS) is a rare hereditary disease affecting multiple systems with predominant involvement of Kidney, Bones and Nails and Eyes. We report a case of NPS which presented as renal failure in a 22 year old male. The patient was admitted with decreased urine output and features of fluid overload and was being evaluated for renal failure. Physical examination revealed associated bony deformities which raised the suspicion of NPS as a possible etiology. This was confirmed by the radiological evaluation which showed the classical features of NPS. Though NPS is a rare clinical condition, physicians should complete knowledge about the components of NPS for appropriate diagnosis and for early detection of other systems involvement

Plasma exosomes protect the myocardium from ischemia-reperfusion injury

BACKGROUND: Exosomes are nanometer-sized vesicles released from cells into the blood, where they can transmit signals throughout the body. Shown to act on the heart, exosomes' composition and the signaling pathways they activate have not been explored. We hypothesized that endogenous plasma exosomes can communicate signals to the heart and provide protection against ischemia and reperfusion injury. OBJECTIVES: This study sought to isolate and characterize exosomes from rats and healthy volunteers, evaluate their cardioprotective actions, and identify the molecular mechanisms involved. METHODS: The exosome-rich fraction was isolated from the blood of adult rats and human volunteers and was analyzed by protein marker expression, transmission electron microscopy, and nanoparticle tracking analysis. This was then used in ex vivo, in vivo, and in vitro settings of ischemia-reperfusion, with the protective signaling pathways activated on cardiomyocytes identified using Western blot analyses and chemical inhibitors. RESULTS: Exosomes exhibited the expected size and expressed marker proteins CD63, CD81, and heat shock protein (HSP) 70. The exosome-rich fraction was powerfully cardioprotective in all tested models of cardiac ischemia-reperfusion injury. We identified a pro-survival signaling pathway activated in cardiomyocytes involving toll-like receptor (TLR) 4 and various kinases, leading to activation of the cardioprotective HSP27. Cardioprotection was prevented by a neutralizing antibody against a conserved HSP70 epitope expressed on the exosome surface and by blocking TLR4 in cardiomyocytes, identifying the HSP70/TLR4 communication axis as a critical component in exosome-mediated cardioprotection. CONCLUSIONS: Exosomes deliver endogenous protective signals to the myocardium by a pathway involving TLR4 and classic cardioprotective HSPs

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Outcomes of salvage radical prostatectomy following more than one failed local therapy

Purpose: To describe the salvage radical prostatectomy (sRP) experience in patients presenting with recurrent, clinically localized prostate cancer after multiple failed local treatments. Materials and Methods: Among the 251 sRP performed during 2000–2016, 11 patients had failed multiple local therapies. We describe baseline clinical characteristics at primary cancer diagnosis and prior to sRP, surgical information, complications and oncological outcomes. Results: The mean±standard deviation age at sRP was 65±5 years and the median (interquartile range) serum prostate-specific antigen (PSA) level was 2 (1.3) ng/mL. The most common first and subsequent treatments were radiotherapy and cryotherapy, respectively, with median time of 24 months from the last local treatment. The median operative time was 180 minutes and median estimated blood loss was 750 mL. Five (45.5%) patients underwent additional procedures during sRP for pre-operative morbidity from prior treatments (rectourethral fistula, urethral stricture, incontinence). Post-operative complications requiring invasive intervention occurred in 7 (63.6%) patients. Over a median follow-up of 29 (12–96) months, 10 of the 11 men (90.9%) achieved an undetectable PSA in after sRP. Three of these men with an initially undetectable PSA level experienced biochemical recurrence; the remaining 7 are without evidence of disease. Overall, no local recurrence or systemic metastasis was identified at last follow-up. Conclusions: sRP is technically feasible and offers durable cancer control in patients with recurrent prostate cancer despite having undergone multiple prior attempts at cure. These patients experience higher rates of post-operative complications and such patients must be appropriately counseled regarding the potential risks and benefits

Can pelvic node dissection at radical prostatectomy influence the nodal recurrence at salvage lymphadenectomy for prostate cancer?

Purpose: To verify the quality of pelvic lymph node dissection (PLND) performed at radical prostatectomy (RP) and its impact on nodal recurrence in patients undergoing salvage lymph node dissection (sLND). Materials and Methods: Retrospective review of 48 patients who underwent sLND for presumed nodal recurrence, to describe the PLND characteristics at RP and correlate the anatomical sites and number of suspicious nodes reported in radiological imaging and final pathology of sLND. Results: Overall, at RP, 8 (16.7%) did not undergo PLND, 32 (66.7%) and 8 (16.7%) received a “limited” (between external iliac vein and obturator nerve) and an “extended” (external iliac, hypogastric, and obturator) dissection, respectively. Median nodes removed during limited and extended dissection were 2 and 24, respectively. At sLND, the mean age was 61.3 years and median prostate specific antigen (PSA) was 1.07 ng/mL. Median nodes removed at sLND were 17 with a median of 2 positive nodes. Recurrent nodes were identified within the template of an extended PLND in 62.5%, 50.0% and 12.5% patients, respectively, following prior no, limited and extended dissection at RP. Recurrence outside the expected lymphatic drainage pathway was noted in 37.5% patients with prior extended dissection at RP. There was a correlation between imaging and pathology specimen in 83% for node location and 58.3% for number of anatomical sites involved. Conclusions: In prostate cancer patients undergoing sLND, most had inadequate PLND at the original RP. Pattern of nodal recurrence may be influenced by the prior dissection and pre sLND imaging appears to underestimate the nodal recurrence

Recovery of urinary continence after radical prostatectomy

INTRODUCTION: In the era of minimally-invasive surgery, urinary incontinence (UI) after radical prostatectomy (RP) still represents a troublesome issue for a considerable rate of patients. Factors associated with the risk of post-RP UI, need to be carefully assessed throughout the overall clinical management process thus including the pre-operative, intra-operative and post-operative setting. AREAS COVERED: This review analyses current published evidences regarding clinical and surgical aspects associated with urinary continence (UC) recovery after RP. A careful evaluation of patient's clinical characteristics should be carried out before surgery in order to properly counsel the patients regarding the risk of UI. In the last two decades, the advent of robotic surgery has led to an overall improvement of functional outcomes after RP, thanks to the development of different surgical strategies based on either the 'preservation' or the 'reconstruction' of the anatomical elements responsible for urinary continence. Finally, several therapeutic strategies including either a conservative approach, or pharmacological and surgical treatments, should be carefully considered for the post-operative management of UI. Expert commentary: A comprehensive pre-operative patient's clinical assessment, along with a proper and well-conducted surgical procedure and an effective post-operative care management are essential element to achieve a high probability of UC recovery

Localized prostate cancer Focal Therapy: "A la carte" Model

La terapia focal se ha instaurado como una alternativa al tratamiento radical en casos seleccionados de cáncer de próstata localizado. La selección de pacientes candidatos a terapia focal se basa en un diagnóstico por imagen apoyado en la resonancia magnética multiparamétrica y las técnicas de fusión de imagen. Debido a los resultados oncológicos y los perfiles de seguridad de series iniciales, se han desarrollado distintas fuentes de energía en los últimos años. La disponibilidad de múltiples tipos de energía para el tratamiento focal, nos compromete a evaluar qué tipo de energía será la óptima según el perfil de paciente y el tipo de lesión. Una energía única para el tratamiento focal sería el ideal, pero ante la investigación de los diversos tipos de energías debemos identificar cuál es la recomendada para cada lesión. Con la experiencia de nuestro centro en distintos abordajes de terapia focal, proponemos el MODELO “À LA CARTE” basado en la localización de la lesión. Presentamos los criterios en los que se basa el modelo “à la carte”, apoyados por la evidencia publicada en el uso de distintos tratamientos ablativos para el tratamiento de cáncer de próstata localizado. Tanto la localización de la lesión, las características técnicas de cada tipo de energía, el perfil del paciente y los efectos secundarios, han de contemplarse en toda elección de tratamiento focal.Focal therapy has settled as an alternative to radical treatment in selected cases of localized prostate cancer. The selection of patients who are candidates for focal therapy is based on imaging diagnosis relying on multiparametric MRI and image fusion techniques. Thanks to the oncological results and safety profiles of initial series, various energy sources have been developed over the last years. The availability of multiple types of energy sources for focal therapy, commits us to evaluate what type of energy would be the optimal depending on patient's profile and type of lesion. A unique energy for focal therapy would be ideal, but facing the research of the various types of energy we must identify which one is recommended for each lesion. With the experience of our center in different approaches of focal therapy we propose the "A LA CARTE" MODEL based on localization of the lesion. We present the criteria the "a la carte" model is based on, supported by the published evidence on the use of different ablative therapies for the treatment of localized prostate cancer. Lesion localization, technical characteristics of each type of energy, patient's profile and secondary effects must be considered in every choice of focal therapy.Sin financiación0.323 JCR (2016) Q4, 73/76 Urology & NephrologyUE

Scoring system for prediction of overall survival in patients with renal cell carcinoma T3aN0M0

Abstract Objective We aim to create a new score to predict postoperative overall survival in patients with nonmetastatic T3aN0 renal cell carcinoma. Methods We reviewed the clinical data of adult patients who underwent radical nephrectomy for renal cell carcinoma between December 2007 and January 2022 in a single tertiary oncological institution. Clinical characteristics, clinical‐pathological staging and histopathological characteristics were analysed. Survival analyses were determined using the Kaplan–Meier curve. A nomogram was established using Cox proportional hazard regression to identify the prognostic factors affecting the overall survival. The area under the curve, calibration curves and decision curve analysis were used to evaluate prognostic efficacy. Results We analyzed 362 patients classified as pT3aN0M0 stage with a median follow‐up of 40 months. According to Cox univariate and multivariate analyses, weight loss greater than 5% in 6 months before surgery, stage V chronic kidney disease after radical nephrectomy, sarcomatoid pattern, and coagulative tumor necrosis were identified as predictors of overall survival. We developed a score and performed internal and external validation. The time‐dependent receiver operating characteristic curve, area under the curve value and calibration curve analysis showed good prediction ability of the score. The nomogram can effectively predict and stratify overall survival after radical nephrectomy in patients with pT3aN0M0 renal cell carcinoma. Conclusion Patients with pT3aN0MO renal cell carcinoma exhibited different characteristics, and those with unfavourable characteristics deserve greater attention during follow‐up. This nomogram provides an accurate prediction of overall survival after radical nephrectomy