Morbidity and mortality of elderly patients with pancreaticobiliary disease according to age and comprehensive geriatric assessment: A prospective observational study / Morbilidad y mortalidad de pacientes de edad avanzada con enfermedad pancreaticobiliar con relación a su edad y la evaluación geriátrica integral: un estudio prospectivo observacional

Background This study was designed to analyze the influence of age and comprehensive geriatric evaluation on clinical results of pancreaticobiliary disease management in elderly patients. Methods A prospective observational study has been undertaken, including 140 elderly patients (over 75 years) with benign pancreaticobiliary disease. Patients were divided according to age in the following groups: group 1: 75–79 years old; group 2: 80–84 years old; group 3: 85 years and older. They underwent a comprehensive geriatric assessment with different scales: Barthel Index, Pfeiffer Index, Charlson Index, and Fragility scale, at admission and had been follow-up 90 days after hospital discharge to analyze its influence on morbidity and mortality. Results Overall, 140 patients have been included (group 1=51; group 2=43 and group 3=46). Most of them, 52 cases (37.8%), had acute cholecystitis, followed by 29 cases of acute cholangitis (20.2%) and acute pancreatitis with 25 cases (17.9%). Significant differences has been observed on complications in different age groups (p=0.033). Especially in patients with a Barthel Index result ≤60, which suggests that these less functional patients had more severe complications after their treatment (p=0.037). The mortality rate was 7.1% (10 patients). Conclusions No significant differences were found between age, morbidity and mortality in elderly patients with pancreaticobiliary disease. Comprehensive geriatric scales showed some utility in their association with specific complications. (AU)

Antecedentes Este estudio fue diseñado para analizar la influencia de la edad y la evaluación geriátrica integral en los resultados clínicos del manejo de la enfermedad pancreatobiliar en pacientes de edad avanzada. Métodos Se ha realizado un estudio observacional prospectivo en el que se incluyeron 140 pacientes de edad avanzada (mayores de 75 años) con enfermedad pancreatobiliar benigna. Los pacientes se dividieron según la edad en los siguientes grupos: Grupo 1: 75-79 años; Grupo 2: 80-84 años; Grupo 3: 85 años y más. Se les realizó una valoración geriátrica integral con diferentes escalas: Barthel Index, Pfeiffer Index, Charlson Index y Fragility scale, al ingreso y seguimiento 90 días después del alta hospitalaria para analizar su influencia en la morbimortalidad. Resultados En total, se incluyeron 140 pacientes (Grupo 1=51; Grupo 2=43 y Grupo 3=46). La mayoría de ellos, 52 casos (37,8%), presentaron colecistitis aguda, seguido de colangitis aguda con 29 casos (20,2%) y pancreatitis aguda con 25 casos (17,9%). Se han observado diferencias significativas en las complicaciones en diferentes grupos de edad (p=0,033). Especialmente en pacientes con un índice de Barthel ≤60, lo que sugiere que estos pacientes menos funcionales tuvieron complicaciones más severas después de su tratamiento (p=0,037). La tasa de mortalidad fue de 7,1% (10 pacientes). Conclusiones No se encontraron diferencias significativas entre la edad, la morbilidad y la mortalidad en pacientes ancianos con enfermedad pancreatobiliar. Las escalas geriátricas integrales mostraron cierta utilidad en su asociación con complicaciones específicas. (AU)

Microfracture-coagulation for the real robotic liver parenchymal transection.

The use of the robotic approach in liver surgery is exponentially increasing. Although technically the robot introduces several innovative features, the instruments linked with the traditional laparoscopic approach for the liver parenchymal transection are not available, which may result in multiple technical variants that may bias the comparative analysis between the different series worldwide. A real robotic approach, minimally efficient for the liver parenchymal transection, with no requirement of external tool, available for the already existing platforms, and applicable to any type of liver resection, counting on the selective use of the plugged bipolar forceps and the monopolar scissors, or "microfracture-coagulation" (MFC) transection method, is described in detail. The relevant aspects of the technique, its indications and methodological basis are discussed.

Diagnosis and clinical management of thrombotic thrombocytopenic purpura (TTP): a consensus statement from the TTP Catalan group.

Thrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an extremely serious condition and, therefore, timely and appropriate treatment is critical to prevent life-threatening complications.Over the past 25 years, significant advances in the understanding of the pathophysiology of immune TTP have led to the development of readily available techniques for measuring ADAMTS13 levels, as well as new drugs that are particularly effective in the acute phase and in preventing relapses. These developments have improved the course of the disease.Given the complexity of the disease and its various clinical and laboratory manifestations, early diagnosis and treatment can be challenging.To address this challenge, a group of experienced professionals from the Catalan TTP group have developed this consensus statement to standardize terminology, diagnosis, treatment and follow up for immune TTP, based on currently available scientific evidence in the field. This guidance document aims to provide healthcare professionals with a comprehensive tool to make more accurate and timely diagnosis of TTP and improve patient outcomes.

Outcome improvement over time in reduced intensity conditioning hematopoietic transplantation: a 20-year experience.

The current study includes all consecutive patients (N = 484) who received a reduced-intensity conditioning regimen (RIC) allogeneic hematopoietic stem cell transplantation in our center from 1999 to 2020. Conditioning regimens were based on fludarabine with melphalan or busulfan, with low-dose thiotepa and pharmacological GVHD prophylaxis consisted of cyclosporine A (CsA)-methotrexate (MTX)/mofetil (MMF) (n = 271), tacrolimus-sirolimus (n = 145), and post-transplantation cyclophosphamide (PTCy)-tacrolimus (n = 68). The median time of overall follow-up in survivors was 8 years (1-22 years) and was at least 3 years in all three GVHD prophylaxis groups. Thirty-three percent had a high or very high disease risk index, 56% ≥ 4 European bone marrow transplantation risk, and 65% ≥ 3 hematopoietic stem cell transplantation comorbidity index score-age score. Neutrophil and platelet engraftment was longer for PTCy-tacro (p 0.0001). Cumulative incidence of grade III-IV aGVHD was 17% at 200 days, and that of moderate-severe cGvHD was 36% at 8 years. GVHD prophylaxis was the only prognostic factor in the multivariable analyses for the development of aGVHD and moderate-severe cGVHD (p 0.0001). NRM and relapse incidences were 29% and 30% at 8 years, while OS and PFS rates were 43% and 39% at 8 years. At 3 years, OS was highest in the PTCy-tacro group (68%) than in the tacro-siro (61%) and CsA-MTX/MMF (49%) cohorts (p < 0.01). In the three groups, respectively, the 200-day incidence of grade III-IV aGvHD (6% vs. 12% vs. 23%) and 3-year moderate-severe cGVHD (8% vs. 40% vs. 38%) were lower in the PTCy cohort. These better outcomes were confirmed in multivariable analyses. Based on our recent results, the PTCy could be considered as a real GvHD prophylaxis in the RIC setting due to improve best 3-year GvHD and survival outcomes.

Resección venosa en cirugía oncológica pancreática: opciones técnicas ante situaciones diversas / Venous resection in pancreatic oncologic surgery: Different techniques for different situations

Introducción: Análisis de los resultados de resección venosa en cirugía pancreática oncológica de 2 centros de referencia. Se analiza el tipo de intervención realizada, los tipos de reconstrucción vascular, el estudio anatomopatológico, la morbimortalidad postoperatoria y la supervivencia a 3 y 5 años. Métodos: Análisis retrospectivo, transversal y comparativo. Se incluyen 41 pacientes intervenidos de lesiones neoplásicas pancreáticas desde 2003 hasta 2021 que requirieron resección venosa por afectación vascular. Resultados: La técnica quirúrgica más frecuente fue la duodenopancreatectomía cefálica tipo Whipple, realizada en 35 de los 41 pacientes (85%). Uno de los casos se realizó por acceso laparoscópico. La reconstrucción vascular tipo 1 (sutura simple) se realizó en 11 pacientes (27%), la tipo 2 (patch de falciforme) en 4 casos (10%), la tipo 3 (sutura término-terminal) en 23 casos (56%) y la reconstrucción tipo 4 (injerto autógeno) en 3 casos (7%). La longitud media del segmento venoso resecado fue de 21mm (11-46) y el tiempo quirúrgico medio fue de 290min (220-360). El 90% (37/41) fueron adenocarcinoma de páncreas. El 83% se consideraron R0 y hubo afectación en el tramo vascular resecado en el 41% de los casos. Hubo morbilidad Clavien-Dindo>3 en 4 pacientes y no hubo ningún caso de mortalidad postoperatoria. La supervivencia a 3 años fue del 48% y a 5 años del 20%. Conclusiones: La resección venosa con reconstrucción para asegurar una resección R0 es una técnica factible, con una aceptable tasa de morbimortalidad y supervivencia global. (AU)

Introduction: To report the clinical results of patients with malignant pancreatic lesions who underwent oncological surgery with vascular resection. The type of intervention performed, the types of vascular reconstruction, the pathological anatomy results, postoperative morbidity and mortality, and survival at 3 and 5 years were analysed. Methods: Retrospective, cross-sectional and comparative analysis. We include 41 patients with malignant pancreatic lesions who underwent surgery with vascular resection due to vascular involvement, from 2013 to 2021. Results: The most performed surgery was the cephalic pancreaticoduodenectomy (Whipple procedure) using median laparotomy, in 35 of the 41 patients (85%). One of the cases in the series was performed laparoscopically. Type 1 reconstruction (simple suture) was performed in 11 (27%) patients, type 2 in 4 (10%) cases, type 3 (T–T suture) in 23 (56%) cases, and type 4 reconstruction by autologous graft in 3 (7%) cases. The mean length of the resected venous segment was 21 (11–46)mm and the mean surgical time was 290 (220–360)min. 90% (37/41) were pancreatic adenocarcinoma. 83% were considered R0 and there was involvement in the resected vascular section in 41% of the cases. Four patients had Clavien-Dindo morbidity>3 and there were no cases of postoperative mortality. Survival at 3 years was 48% and at 5 years was 20%. Conclusions: The aggressive surgical treatment with venous resection in pancreatic malignant lesions to ensure R0 and its vascular reconstruction is a feasible technique, with an acceptable morbid-mortality rate and overall survival. (AU)

Child dental neglect and legal protections: a compendium of briefs from policy reviews in 26 countries and a special administrative region of China.

Background: Child neglect is a public health, human rights, and social problem, with potentially devastating and costly consequences. The aim of this study was to: (1) summarize the oral health profile of children across the globe; (2) provide a brief overview of legal instruments that can offer children protection from dental neglect; and (3) discuss the effectiveness of these legal instruments. Methods: We summarized and highlighted the caries profile and status of implementation of legislation on child dental neglect for 26 countries representing the World Health Organization regions: five countries in Africa (Nigeria, South Africa, Sudan, Tanzania, Zimbabwe), eight in the Americas (Argentina, Brazil, Canada, Chile, Mexico, Peru, Unites States of America, Uruguay), six in the Eastern Mediterranean (Egypt, Iran, Libya, Jordan, Qatar, Saudi Arabia), four in Europe (Italy, Latvia, Serbia, United Kingdom), two in South-East Asia (India and Indonesia) and one country (China) with its special administrative region (Hong Kong) in the Western Pacific. Results: Twenty-five of the 26 countries have legal instruments to address child neglect. Only two (8.0%) of these 25 countries had specific legal instruments on child dental neglect. Although child neglect laws can be interpreted to establish a case of child dental neglect, the latter may be difficult to establish in countries where governments have not addressed barriers that limit children's access to oral healthcare. Where there are specific legal instruments to address child dental neglect, a supportive social ecosystem has also been built to facilitate children's access to oral healthcare. A supportive legal environment, however, does not seem to confer extra protection against risks for untreated dental caries. Conclusions: The institution of specific country-level legislation on child dental neglect may not significantly reduce the national prevalence of untreated caries in children. It, however, increases the prospect for building a social ecosystem that may reduce the risk of untreated caries at the individual level. Social ecosystems to mitigate child dental neglect can be built when there is specific legislation against child dental neglect. It may be more effective to combine public health and human rights-based approaches, inclusive of an efficient criminal justice system to deal with child dental neglect.

Cirugía robótica hepática: una nueva realidad. Análisis descriptivo de 220 casos de cirugía hepática mínimamente invasiva en 182 pacientes / Robotic liver surgery: A new reality. Descriptive analysis of 220 cases of minimally invasive liver surgery in 182 patients

Introducción El nivel de recomendación del abordaje robótico en la cirugía hepática es controvertido. Se realiza un análisis descriptivo, retrospectivo yunicéntrico de los resultados a corto plazo de la cirugía hepática robótica y laparoscópica en un mismo periodo.MétodosAnálisis descriptivo del abordaje robótico y laparoscópico sobre 220 resecciones en 182 pacientes sometidos a cirugía hepática mínimamente invasiva.ResultadosEntre abril de 2018 y junio de 2022 se realizaron 92 resecciones hepáticas robóticas (RHR) en 83 pacientes y 128 laparoscópicas (RHL) en 99 pacientes. Se observaron más resecciones mayores (p<0,001) y más resecciones múltiples (p=0,002) en el grupo CHL. El porcentaje de resecciones anatómicas fue similar (RHR: 64,1 vs. RHL: 56,3%). En el grupo CHL el tiempo medio operatorio fue de 212min (DE: 52,1), las pérdidas hemáticas de 276,5ml (100-1.000) y la tasa de conversión del 12,1%. La estancia media hospitalaria fue de 5,7 días (DE: 4,9), la morbilidad fue del 27,3%, con un 2% de mortalidad. En el grupo CHR el tiempo medio operatorio fue de 217min (DE: 53,6), las pérdidas hemáticas fueron de 169,5ml (100-900) y la tasa de conversión del 2,5%. La estancia media hospitalaria fue de 4,1 días (DE: 2,1) y la morbilidad fue del 15%, con mortalidad nula.ConclusiónLa cirugía mínimamente invasiva hepática es una técnica segura y reproducible. La CHR permite realizar resecciones hepáticas con seguridad y parece ser una técnica no inferior a la CHL, pero para determinar el abordaje mínimamente invasivo de elección en cirugía hepática se requieren estudios aleatorizados. (AU)

Introduction The level of recommendation of the robotic approach in liver surgery is controversial. The objective of the study is to carry out a single-center retrospective descriptive analysis of the short-term results of the robotic and laparoscopic approach in liver surgery during the same period.MethodsDescriptive analysis of the short-term results of the robotic and laparoscopic approach on 220 resections in 182 patients undergoing minimally invasive liver surgery.ResultsBetween April 2018 and June 2022, a total of 92 robotic liver resections (RLR) were performed in 83 patients and 128 laparoscopic (LLR) in 99 patients. The LLR group showed a higher proportion of major surgery (P<.001) and multiple resections (P=.002). The two groups were similar in anatomical resections (RLR 64.1% vs. LLR 56.3%). In the LLS group, the average operating time was 212min (SD 52.1). Blood loss was 276.5ml (100-1000) and conversion 12.1%. Mean hospital stay was 5.7 (SD 4.9) days. Morbidity was 27.3% and 2% mortality. In the RLS group, the mean operative time was 217min (SD 53.6), blood loss 169.5ml (100.900), and conversion 2.5%. Mean hospital stay was 4.1 (SD 2.1) days. Morbidity was 15%, with no mortality.ConclusionMinimally invasive liver surgery is a safe technique, and in particular, RLS allows liver resections to be performed safely and reproducibly; it appears to be a non-inferior technique to LLS, but randomized studies are needed to determine the minimally invasive approach of choice in liver surgery. (AU)

Pancreatectomía corporocaudal laparoscópica y robótica, de elección y de futuro / Laparoscopic and robotic distal pancreatectomy: The choice and the future

Introducción La pancreatectomía distal (PD) mínimamente invasiva (MIS) está actualmente bien establecida, ya sea mediante técnica laparoscópica (PDL) o robótica (PDR).MétodosDe 83 PD realizadas entre enero del 2018 y marzo del 2022, se realizaron 57 casos (68,7%) mediante MIS, 35 PDL y 22 PDR (da Vinci Xi). Se evalúa la experiencia de ambos procedimientos y el valor del abordaje robótico. Se analizan en detalle los casos de conversión.ResultadosEl tiempo quirúrgico medio en las PDL y PDR fue de 201,2 (DE 47,8) y 247,54 (DE 35,8) min, (p=0,486). No se observaron diferencias en estancia hospitalaria ni en tasa de conversión, 6 (5-34) vs. 5,6 (5-22) días y 4 (11,4%) vs. 3 (13,6%) casos, respectivamente, (p=0.126). La tasa de reingresos fue de 3/35 (11,4%) y 6/22 (27,3%) casos, PDL vs. PDR respectivamente, (p=0.126).No existieron diferencias en morbilidad (Dindo-Clavien ≥ III) entre ambos grupos. La mortalidad fue de un caso en el grupo robótico (un paciente con conversión precoz por afectación vascular). La tasa de resecciones R0 fue mayor en el grupo robótico (77,1% vs. 90,9%) alcanzando la significación estadística, p=0,04.ConclusionesLa PDMIS es un procedimiento seguro y factible en pacientes seleccionados. Una planificación quirúrgica y la implementación escalonada basada en la experiencia previa ayudan a afrontar procedimientos técnicamente exigentes. Se sugiere que la PDR podría ser el abordaje de elección en la pancreatectomía corporocaudal, no siendo inferior a la PDL. (AU)

Introduction Distal pancreatectomy (DP) is currently well established as a minimally invasive surgery (MIS) procedure, using either a laparoscopic (LDP) or robotic (RDP) approach.MethodsOut of 83 DP performed between January 2018 and March 2022, 57 cases (68.7%) were performed using MIS: 35 LDP and 22 RDP (da Vinci Xi). We have assessed the experience with the 2techniques and analyzed the value of the robotic approach. Cases of conversion have been examined in detail.ResultsThe mean operative times for LDP and RDP were 201.2 (SD 47.8) and 247.54 (SD 35.8)min, respectively (p=0,486). No differences were observed in length of hospital stay or conversion rate: 6 (5–34) vs. 5.6 (5–22) days, and 4 (11.4%) vs. 3 (13.6%) cases, respectively (p=0.126). The readmission rate was 3/35 patients (11.4%) treated with LDP and 6/22 (27.3%) cases of RDP (p=0.126).There were no differences in morbidity (Dindo-Clavien≥III) between the 2groups. Mortality was one case in the robotic group (a patient with early conversion due to vascular involvement). The rate of R0 resection was greater and statistically significant in the RDP group (77.1% vs. 90.9%) (P=,04).ConclusionsMinimally invasive distal pancreatectomy (MIDP) is a safe and feasible procedure in selected patients. Surgical planning and stepwise implementation based on prior experience help surgeons successfully perform technically demanding procedures. RDP could be the approach of choice in distal pancreatectomy, and it is not inferior to LDP. (AU)

Haematological and other manifestations in the presence of antiphospholipid antibodies in a multicentric paediatric cohort.

OBJECTIVES: To identify the variables associated with the development of haematological manifestations in the presence of antiphospholipid antibodies (aPLs) in a paediatric cohort. METHODS: We conducted a multicentric retrospective cohort study of children under the age of 18 years. RESULTS: One hundred and thirty-four children were included; 12.2% had at least one thrombotic event (TE) and 67% at least one non-criterion manifestation. Of them, 90% did not develop any TE. Haematological manifestations were the most frequent (42%), followed by neurological (19.8%), cutaneous (17.6%), cardiac (16.8%) and renal (1.5%) manifestations. In those children with haematological disorders, the aPLs positivity rate was: 67.3% LA, 65.6% aß2GPI, 60% aCL, 45.5% single, 23.6% double and 30.9% triple. A univariate analysis showed that children with IgM aCL+, IgM aß2GPI+, triple positivity and with a SLE diagnosis had a significantly higher frequency of haematological manifestations (p<0.05). Finally, a stepwise regression analysis identified IgG aß2GPI positivity [OR 2.91, 95% CI (1.26-6.74), p=0.013], SLE [OR 2.67, 95% CI (1.13-6.3), p=0.026] and LA positivity [OR 2.53, 95% CI (1.08-5.94), p=0.033] as independent risk factors for the development of haematological manifestations. CONCLUSIONS: Non-criteria manifestations and among them haematological disorders, are the most frequent events in the presence of aPLs and/or LA in our paediatric cohort. Children with SLE, LA and/or IgG aß2GPI positivity showed a higher risk of haematological manifestations.

Morbidity and mortality of elderly patients with pancreaticobiliary disease according to age and comprehensive geriatric assessment: A prospective observational study.

BACKGROUND: This study was designed to analyze the influence of age and comprehensive geriatric evaluation on clinical results of pancreaticobiliary disease management in elderly patients. METHODS: A prospective observational study has been undertaken, including 140 elderly patients (over 75 years) with benign pancreaticobiliary disease. Patients were divided according to age in the following groups: group 1: 75-79 years old; group 2: 80-84 years old; group 3: 85 years and older. They underwent a comprehensive geriatric assessment with different scales: Barthel Index, Pfeiffer Index, Charlson Index, and Fragility scale, at admission and had been follow-up 90 days after hospital discharge to analyze its influence on morbidity and mortality. RESULTS: Overall, 140 patients have been included (group 1=51; group 2=43 and group 3=46). Most of them, 52 cases (37.8%), had acute cholecystitis, followed by 29 cases of acute cholangitis (20.2%) and acute pancreatitis with 25 cases (17.9%). Significant differences has been observed on complications in different age groups (p=0.033). Especially in patients with a Barthel Index result ≤60, which suggests that these less functional patients had more severe complications after their treatment (p=0.037). The mortality rate was 7.1% (10 patients). CONCLUSIONS: No significant differences were found between age, morbidity and mortality in elderly patients with pancreaticobiliary disease. Comprehensive geriatric scales showed some utility in their association with specific complications.

Metal ion content of internal organs in the calorically restricted Wistar rat.

BACKGROUND: Despite the agreed principle that access to food is a human right, undernourishment and metal ion deficiencies are public health problems worldwide, exacerbated in impoverished or war-affected areas. It is known that maternal malnutrition causes growth retardation and affects behavioral and cognitive development of the newborn. Here we ask whether severe caloric restriction leads per se to disrupted metal accumulation in different organs of the Wistar rat. METHODS: Inductively coupled plasma optical emission spectroscopy was used to determine the concentration of multiple elements in the small and large intestine, heart, lung, liver, kidney, pancreas, spleen, brain, spinal cord, and three skeletal muscles from control and calorically restricted Wistar rats. The caloric restriction protocol was initiated from the mothers prior to mating and continued throughout gestation, lactation, and post-weaning up to sixty days of age. RESULTS: Both sexes were analyzed but dimorphism was rare. The pancreas was the most affected organ presenting a higher concentration of all the elements analyzed. Copper concentration decreased in the kidney and increased in the liver. Each skeletal muscle responded to the treatment differentially: Extensor Digitorum Longus accumulated calcium and manganese, gastrocnemius decreased copper and manganese, whereas soleus decreased iron concentrations. Differences were also observed in the concentration of elements between organs independently of treatment: The soleus muscle presents a higher concentration of Zn compared to the other muscles and the rest of the organs. Notably, the spinal cord showed large accumulations of calcium and half the concentration of zinc compared to brain. X-ray fluorescence imaging suggests that the extra calcium is attributable to the presence of ossifications whereas the latter finding is attributable to the low abundance of zinc synapses in the spinal cord. CONCLUSION: Severe caloric restriction did not lead to systemic metal deficiencies but caused instead specific metal responses in few organs.

Realidad aumentada en cirugía hepato-bilio-pancreática. Una tecnología al alcance de la mano / Augmented reality in hepatobiliary-pancreatic surgery: A technology at your fingertips

La realidad aumentada es una tecnología que abre nuevas posibilidades en cirugía. Se presenta su implementación en una unidad de cirugía hepato-bilio-pancreática en relación con la planificación preoperatoria, el soporte intraoperatorio y la docencia. Para la planificación quirúrgica se han utilizado reconstrucciones 3D de la TC y de la RMN para hacer una evaluación de casos complejos, siendo la interpretación de la anatomía más precisa, y la planificación de la técnica más simple. A nivel intraoperatorio ha permitido la conexión remota holográfica entre especialistas, la substitución de elementos físicos por elementos virtuales, y el uso de modelos virtuales de consulta y guía quirúrgica. En docencia se han impartido clases que incluyen la retransmisión de una cirugía con el soporte de elementos virtuales para una mejor comprensión por parte de los estudiantes. Siendo la experiencia satisfactoria, la realidad aumentada podría aplicarse en el futuro de la cirugía hepato-bilio-pancreática para mejorar sus resultados. (AU)

Augmented reality is a technology that opens new possibilities in surgery. Its implementation in a hepatobiliary-pancreatic surgery unit is presented in relation to preoperative planning, intraoperative support and teaching. For surgical planning, 3D CT and MRI reconstructions have been used to evaluate complex cases, making the interpretation of the anatomy more precise and the planning of the technique simpler. At an intraoperative level, it has allowed remote holographic connection between specialists, the substitution of physical elements for virtual elements, and the use of virtual consultation models and surgical guides. In teaching, new lessons include the retransmission of a surgery with the support of virtual elements for a better understanding by the students. Being the experience satisfactory, augmented reality could be applied in the future of hepatobiliary-pancreatic surgery to improve its results. (AU)

Randomized phase II study of weekly carfilzomib 70 mg/m2 and dexamethasone with or without cyclophosphamide in relapsed and/or refractory multiple myeloma patients.

In this randomized phase II study (GEM-KyCyDex, clinicaltrials gov. Identifier: NCT03336073), the combination of weekly carfilzomib 70 mg/m2, cyclophosphamide and dexamethasone (KCd) was compared to carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines (PL). One hundred and ninety-seven patients were included and randomized 1:1 to receive KCd (97 patients) or Kd (100 patients) in 28-day cycles until progressive disease or unacceptable toxicity occurred. Patient median age was 70 years, and the median number of PL was one (range, 1-3). More than 90% of patients had previously been exposed to proteasome inhibitors, approximetely 70% to immunomodulators, and approximetely 50% were refractory to their last line (mainly lenalidomide) in both groups. After a median follow-up of 37 months, median progression-free survival (PFS) was 19.1 and 16.6 months in KCd and Kd, respectively (P=0.577). Of note, in the post hoc analysis of the lenalidomide-refractory population, the addition of cyclophosphamide to Kd resulted in a significant benefit in terms of PFS: 18.4 versus 11.3 months (hazard ratio =1.7, 95% confidence interval: 1.1-2.7; P=0.043). The overall response rate and the percentage of patients who achieved complete response was around 70% and 20% in both groups. The addition of cyclophosphamide to Kd did not result in any safety signal, except for severe infections (7% vs. 2%). In conclusion, the combination of cyclophosphamide with Kd 70 mg/m2 weekly does not improve outcomes as compared with Kd alone in RRMM after 1-3 PL, but a significant benefit in PFS was observed with the triplet combination in the lenalidomide-refractory population. The administration of weekly carfilzomib 70 mg/m2 was safe and convenient, and, overall, the toxicity was manageable in both arms.

Successful Outcome in Patients with Myelofibrosis Undergoing Allogeneic Donor Hematopoietic Cell Transplantation Using Reduced Doses of Post-Transplantation Cyclophosphamide: Challenges and Review of the Literature.

Engraftment and nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT) depend greatly on the transplantation platform in patients with myelofibrosis (MF). We report outcomes of 14 consecutive MF patients who received reduced doses of post-transplantation cyclophosphamide (PTCy; 60 mg/kg total dose) and tacrolimus as graft-versus-host disease (GVHD) prophylaxis as part of a new standardized allo-HCT protocol. The median patient age at allo-HCT was 59 years (range, 41 to 67 years), and the median interval from diagnosis to HCT was 19 months (range, 2 to 114 months). All patients received ruxolitinib before HCT, and 71% had no response. Most patients (78%) had symptomatic splenomegaly at HCT. Eighty-six percent received reduced-intensity conditioning, and 64% underwent allo-HCT from an unrelated donor. There were no graft failures, and neutrophil and platelet recovery occurred at a median of 21 days and 31 days, respectively. The cumulative incidence of grade II-IV acute GVHD was 28.6%, and that of grade III-IV acute GVHD was 7%. The 2-year incidence of overall and moderate-severe chronic GVHD was 36% and 14%, respectively. Only 1 patient relapsed after transplantation, and NRM was 7% at 100 days and 14% at 2 years. The GVHD-free/relapse-free and immunosuppression-free incidence at 1 year was 41%. With a median follow-up for survivors of 28 months (range, 8 to 55 months), the 2-year overall survival and progression-free survival were 86% and 69%, respectively. Reduced doses of PTCy as GVHD prophylaxis for high-risk MF patients showed promising results by reducing the incidence of GVHD without any cases of graft failure.

Laparoscopic and robotic distal pancreatectomy: the choice and the future.

INTRODUCTION: Distal pancreatectomy (DP) is currently well established as a minimally invasive surgery (MIS) procedure, using either a laparoscopic (LDP) or robotic (RDP) approach. METHODS: Out of 83 DP performed between January 2018 and March 2022, 57 cases (68.7%) were performed using MIS: 35 LDP and 22 RDP (da Vinci Xi). We have assessed the experience with the two techniques and analyzed the value of the robotic approach. Cases of conversion have been examined in detail. RESULTS: The mean operative times for LDP and RDP were 201.2 (SD 47.8) and 247.54 (SD 35.8) minutes, respectively (P = NS). No differences were observed in length of hospital stay or conversion rate: 6 (5-34) vs. 5.6 (5-22) days, and 4 (11.4%) vs. 3 (13.6%) cases, respectively (P = NS). The readmission rate was 3/35 patients (11.4%) treated with LDP and 6/22 (27.3%) cases of RDP (P = NS). There were no differences in morbidity (Dindo-Clavien ≥ III) between the two groups. Mortality was one case in the robotic group (a patient with early conversion due to vascular involvement). The rate of R0 resection was greater and statistically significant in the RDP group (77.1% vs. 90.9%) (P = .04). CONCLUSION: Minimally invasive distal pancreatectomy (MIDP) is a safe and feasible procedure in selected patients. Surgical planning and stepwise implementation based on prior experience help surgeons successfully perform technically demanding procedures. RDP could be the approach of choice in distal pancreatectomy, and it is not inferior to LDP.

Robotic liver surgery: A new reality. Descriptive analysis of 220 cases of minimally invasive liver surgery in 182 patients.

INTRODUCTION: The level of recommendation of the robotic approach in liver surgery is controversial. The objective of the study is to carry out a single-center retrospective descriptive analysis of the short-term results of the robotic and laparoscopic approach in liver surgery during the same period. METHODS: Descriptive analysis of the short-term results of the robotic and laparoscopic approach on 220 resections in 182 patients undergoing minimally invasive liver surgery. RESULTS: Between April 2018 and June 2022, a total of 92 robotic liver resections (RLR) were performed in 83 patients and 128 laparoscopic (LLR) in 99 patients. The LLR group showed a higher proportion of major surgery (P < .001) and multiple resections (P = .002). The two groups were similar in anatomical resections (RLR 64.1% vs. LLR 56.3%). In the LLS group, the average operating time was 212 min (SD 52.1). Blood loss was 276.5 mL (100-1000) and conversion 12.1%. Mean hospital stay was 5.7 (SD 4.9) days. Morbidity was 27.3% and 2% mortality. In the RLS group, the mean operative time was 217 min (SD 53.6), blood loss 169.5 mL (100.900), and conversion 2.5%. Mean hospital stay was 4.1 (SD 2.1) days. Morbidity was 15%, with no mortality. CONCLUSION: Minimally invasive liver surgery is a safe technique, and in particular, RLS allows liver resections to be performed safely and reproducibly; it appears to be a non-inferior technique to LLS, but randomized studies are needed to determine the minimally invasive approach of choice in liver surgery.

Augmented reality in hepatobiliary-pancreatic surgery: a technology at your fingertips.

Augmented reality is a technology that opens new possibilities in surgery. We present our experience in a hepatobiliary-pancreatic surgery unit in terms of preoperative planning, intraoperative support and teaching. For surgical planning, we have used 3D CT and MRI reconstructions to evaluate complex cases, which has made the interpretation of the anatomy more precise and the planning of the technique simpler. At an intraoperative level, it provides for remote holographic connection between specialists, the substitution of physical elements for virtual elements, and the use of virtual consultation models and surgical guides. In teaching, new lessons include sharing live video of surgery with the support of virtual elements for a better student understanding. As the experience has been satisfactory, augmented reality could be applied in the future to improve the results of hepatobiliary-pancreatic surgery.

BCKDK deficiency: a treatable neurodevelopmental disease amenable to newborn screening.

There are few causes of treatable neurodevelopmental diseases described to date. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder characterized by autism, intellectual disability and microcephaly. We report the largest cohort of patients studied, broadening the phenotypic and genotypic spectrum. Moreover, this is the first study to present newborn screening findings and mid-term clinical outcome. In this cross-sectional study, patients with a diagnosis of BCKDK deficiency were recruited via investigators' practices through a MetabERN initiative. Clinical, biochemical and genetic data were collected. Dried blood spot (DBS) newborn screening (NBS) amino acid profiles were retrieved from collaborating centres and compared to a healthy newborn reference population. Twenty-one patients with BCKDK mutations were included from 13 families. Patients were diagnosed between 8 months and 16 years (mean: 5.8 years, 43% female). At diagnosis, BCAA levels (leucine, valine and isoleucine) were below reference values in plasma and in CSF. All patients had global neurodevelopmental delay; 18/21 had gross motor function (GMF) impairment with GMF III or worse in 5/18, 16/16 intellectual disability, 17/17 language impairment, 12/17 autism spectrum disorder, 9/21 epilepsy, 12/15 clumsiness, 3/21 had sensorineural hearing loss and 4/20 feeding difficulties. No microcephaly was observed at birth, but 17/20 developed microcephaly during follow-up. Regression was reported in six patients. Movement disorder was observed in 3/21 patients: hyperkinetic movements (1), truncal ataxia (1) and dystonia (2). After treatment with a high-protein diet (≥ 2 g/kg/day) and BCAA supplementation (100-250 mg/kg/day), plasma BCAA increased significantly (P < 0.001), motor functions and head circumference stabilized/improved in 13/13 and in 11/15 patients, respectively. Among cases with follow-up data, none of the three patients starting treatment before 2 years of age developed autism at follow-up. The patient with the earliest age of treatment initiation (8 months) showed normal development at 3 years of age. NBS in DBS identified BCAA levels significantly lower than those of the normal population. This work highlights the potential benefits of dietetic treatment, in particular early introduction of BCAA. Therefore, it is of utmost importance to increase awareness about this treatable disease and consider it as a candidate for early detection by NBS programmes.