Diarrea crónica en paciente inmunocompetente / Chronic diarrhea in an immunocompetent patient

Presentamos un caso de diarrea crónica en un paciente varón de 58 años que no tenía antecedentes personales de interés ni alteraciones conocidas en su estado inmunitario. (AU)

We present a case of chronic diarrhea in a 58-year-old male patient with no relevant personal history and no known alterations in his immune status. (AU)

Placenta Accreta in a COVID-19 positive patient

Placenta accreta spectrum is a state of abnormal attachment of the placenta to the myometrium, resulting in hemorrhage and delayed or impossible delivery of the placenta. It`s an infrequent pathology, and this condition can be life-threatening. We present an interesting case of a 41-year-old female with COVID-19 that attends the emergency room due to scanty vaginal bleeding at 14 days postpartum. A hemostatic hysterectomy was performed, and the diagnosis of placenta accreta was made. (AU)

Lesiones osteolíticas multifocales / Multifocal osteolytic lesions

A 79-year-old woman with multiple pathologies and multiple osteolytic lesions during the Covid-19 pandemic. Histopathological and radiological differential diagnosis of injuries. (AU)

First Precision Measurement of the Parity Violating Asymmetry in Cold Neutron Capture on

We report the first precision measurement of the parity-violating asymmetry in the direction of proton momentum with respect to the neutron spin, in the reaction ^{3}He(n,p)^{3}H, using the capture of polarized cold neutrons in an unpolarized active ^{3}He target. The asymmetry is a result of the weak interaction between nucleons, which remains one of the least well-understood aspects of electroweak theory. The measurement provides an important benchmark for modern effective field theory and potential model calculations. Measurements like this are necessary to determine the spin-isospin structure of the hadronic weak interaction. Our asymmetry result is A_{PV}=[1.55±0.97(stat)±0.24(sys)]×10^{-8}, which has the smallest uncertainty of any hadronic parity-violating asymmetry measurement so far.

La mortalidad del primer cuatrimestre de 2020 en la pandemia por COVID-19. Análisis del Comité de Mortalidad del Hospital Central de la Defensa «Gómez Ulla», Madrid / Mortality in the first four months of 2020 in the COVID-19 pandemic. Analysis of the Mortality Committee of the Hospital Central de la Defensa «Gómez Ulla», Madrid

INTRODUCCIÓN: En diciembre de 2019, Wuhan, China, tuvo un brote de la enfermedad COVID-19, causado por el síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2). La enfermedad en poco tiempo se convirtió en pandemia. Los factores de riesgo asociados a su mortalidad están aún por determinar. El Comité de Mortalidad estudia los fallecimientos hospitalarios con el objetivo principal de reducir las muertes evitables. OBJETIVOS: Describir las características de comorbilidad y demográficas de los exitus del primer cuatrimestre de 2020 en el Hospital Central de la Defensa y su relación con COVID-19. MATERIAL Y MÉTODOS: Estudio transversal, descriptivo, observacional y retrospectivo. Datos clínicos y demográficos de los exitus en relación a la presencia de COVID-19. RESULTADOS: De 371 fallecidos, 271 COVID-19 positivos y 100 COVID-19 negativos. Casi 1,8 veces más de la mortalidad esperada en el cuatrimestre (208 a 371). Edad media de los grupos 80 y 84 años, rango entre 35 y 104 años. Estancia hospitalaria en COVID-19 positivos del 10,1% frente a 5,5% en COVID-19 negativos. Exitus extranjeros menor de 70 años 80%. Lugar del exitus: planta hospitalaria (84%). Puntuación media del índice de Charlson: 4 puntos (intercuartil, 2-6), 53% supervivencia estimada a 10 años. Comorbilidades más frecuentes: HTA (70,5%); DM (36,5%); Oncológico (31%); Neumonía (86,7%). Mal estado general al ingreso (81,9%). CONCLUSIONES: La variable con mayor potencia relacionada con la mortalidad fue la edad avanzada. Otro grupo, sin comorbilidades, menor de 51 años, presentó evolución fatal. A pesar de la dificultad para establecer la tasa de mortalidad real por COVID-19, la diferencia entre los exitus esperados y los registrados por el Comité de Mortalidad Hospitalario constituye el valor más aproximado

INTRODUCTION: In December 2019, Wuhan, China had an outbreak of the COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease quickly turned into a pandemic. The risk factors associated with its mortality are yet to be determined. The Mortality Committee studies hospital deaths with the main objective of reducing preventable deaths. OBJECTIVES: To describe the comorbidity and demographic characteristics of the deaths from the first four-month period of 2020 at the Central Defense Hospital and their relationship with COVID-19. MATERIAL AND METHODS: Cross-sectional, descriptive, observational and retrospective study. Clinical and demographic data of deaths in relation to the presence of COVID-19. RESULTS: Of 371 deceased, 271 positive COVID-19 and 100 negative COVID-19-. Almost 1.8 times more than the expected mortality in the four-month period (208 to 371). Average age of the groups 80 and 84 years, range between 35 and 104 years. Hospital stay at positive COVID-19 10.1% compared to 5.5% at negative COVID-19. Foreign exitus under 70 years 80%. Exit location: hospital plant (84%). Average Charlson index score: 4 points (interquartile, 2-6), 53% estimated survival at 10 years. Most frequent comorbidities: HTN (70.5%); DM (36.5%); Oncological (31%); Pneumonia (86.7%). Poor general condition at admission (81.9%). CONCLUSIONS: The variable with the greatest power related to mortality was advanced age. Another group, without comorbidities, younger than 51 years, presented fatal evolution. Despite the difficulty in establishing the actual mortality rate from COVID-19, the difference between the expected deaths and those recorded by the Hospital Mortality Committee constitutes the most approximate value

Cardiotoxicity and pro-inflammatory effects of the immune checkpoint inhibitor Pembrolizumab associated to Trastuzumab.

BACKGROUND: The immunotherapy has revolutionized the world of oncology in the last decades with considerable advantages in terms of overall survival in cancer patients. The association of Pembrolizumab and Trastuzumab was recently proposed in clinical trials for the treatment of Trastuzumab-resistant advanced HER2-positive breast cancer. Although immunotherapies are frequently associated with a wide spectrum of immune-related adverse events, the cardiac toxicity has not been properly studied. PURPOSE: We studied, for the first time, the putative cardiotoxic and pro-inflammatory effects of Pembrolizumab associated to Trastuzumab. METHODS: Cell viability, intracellular calcium quantification and pro-inflammatory studies (analyses of the production of Interleukin 1ß, 6 and 8, the expression of NF-kB and Leukotriene B4) were performed in human fetal cardiomyocytes. Preclinical studies were also performed in C57BL6 mice by analyzing fibrosis and inflammation in heart tissues. RESULTS: The combination of Pembrolizumab and Trastuzumab leads to an increase of the intracellular calcium overload (of 3 times compared to untreated cells) and to a reduction of the cardiomyocytes viability (of 65 and 20-25%, compared to untreated and Pembrolizumab or Trastuzumab treated cells, respectively) indicating cardiotoxic effects. Notably, combination therapy increases the inflammation of cardiomyocytes by enhancing the expression of NF-kB and Interleukins. Moreover, in preclinical models, the association of Pembrolizumab and Trastuzumab increases the Interleukins expression of 40-50% compared to the single treatments; the expression of NF-kB and Leukotriene B4 was also increased. CONCLUSION: Pembrolizumab associated to Trastuzumab leads to strong cardiac pro-inflammatory effects mediated by overexpression of NF-kB and Leukotriene B4 related pathways.

Low doses of Bisphenol A have pro-inflammatory and pro-oxidant effects, stimulate lipid peroxidation and increase the cardiotoxicity of Doxorubicin in cardiomyoblasts.

Endocrine disrupters are strictly associated to cancer and several cardiovascular risk factors. Bisphenol A (BPA) is an endocrine disrupter commonly used in the manufacturing of plastics based on polycarbonate, polyvinyl chloride and resins. Our study aims to investigate whether BPA may cause pro-oxidative and pro-inflammatory effects on cardiomyoblasts, thus exacerbating the Doxorubicin (DOXO)-induced cardiotoxicity phenomena. We tested the metabolic effects of BPA at low doses analyzing its affections on the intracellular calcium uptake, oxidative stress, lipid peroxidation and production of nitric oxide and interleukins. Co-incubation of BPA and DOXO significantly reduced the cardiomyoblast viability, compared to only DOXO exposure cells. The mechanisms underlying these effects are based on the stimulation of the intracellular calcium accumulation and lipid peroxidation. Notably, BPA increase the production of pro-inflammatory interleukins involved in cardiovascular diseases as well as in DOXO-Induced cardiotoxicity phenomena. This study provides a rationale for translational studies in the field of cardio-oncology.

First Observation of P-odd γ Asymmetry in Polarized Neutron Capture on Hydrogen.

We report the first observation of the parity-violating gamma-ray asymmetry A_{γ}^{np} in neutron-proton capture using polarized cold neutrons incident on a liquid parahydrogen target at the Spallation Neutron Source at Oak Ridge National Laboratory. A_{γ}^{np} isolates the ΔI=1, ^{3}S_{1}→^{3}P_{1} component of the weak nucleon-nucleon interaction, which is dominated by pion exchange and can be directly related to a single coupling constant in either the DDH meson exchange model or pionless effective field theory. We measured A_{γ}^{np}=[-3.0±1.4(stat)±0.2(syst)]×10^{-8}, which implies a DDH weak πNN coupling of h_{π}^{1}=[2.6±1.2(stat)±0.2(syst)]×10^{-7} and a pionless EFT constant of C^{^{3}S_{1}→^{3}P_{1}}/C_{0}=[-7.4±3.5(stat)±0.5(syst)]×10^{-11} MeV^{-1}. We describe the experiment, data analysis, systematic uncertainties, and implications of the result.

[Obstetrical prognosis of patients after a previous caesarean section performed before 32 weeks of amenorrhea]. / Pronostic obstétrical des patientes présentant un antécédent de césarienne réalisée avant 32 semaines d'aménorrhée.

OBJECTIVE: To assess delivery mode, maternal morbidity including uterine rupture and scar dehiscence and neonatal outcome, during a pregnancy after a previous caesarean delivery before 32 weeks of amenorrhea. METHODS: A retrospective descriptive study was carried out at the Besançon University Hospital during an 8-year period. We identified 292 consecutive patients presenting a singleton pregnancy delivery before 32 weeks of amenorrhea. We analysed the next pregnancy. Patients presenting more than one caesarean section were excluded from this study. RESULTS: Out of the 292 patients, 62 met inclusion criteria. The average gestational age of the first caesarean section was 29 weeks and 3 days. Among these patients, 17 (27.4%) had a planned caesarean delivery after caesarean (CDAC) and 45 (72.6%) had a trial of vaginal delivery (TVD) with a success rate of 71.1%, that is a total of 51.6% of vaginal delivery after a previous early caesarean section. In case of a failed TVD, arterial pH (P<0.005), Apgar score at one minute (P<0.05) and at 10minutes (P<0.05) were significantly lower compared to the CDAC group. Regarding perinatal outcome, there was no significant difference (P=0.31) between the groups in intention to treat. The only uterine rupture (1.6%) was noticed during a caesarean section at 26 weeks and 3 days, in a patient initially included in the TVD group. Five uterine scar-dehiscences (8.1%) were discovered including 80% during caesarean section, at an average term of 32 weeks and 2 days of amenorrhea. CONCLUSION: After an early caesarean section, trial of vaginal delivery can be implemented if local conditions are favorable. There is no difference in maternal morbidity, success of labour and neonatal outcome if previous caesarean section was performed before 32 weeks or at term. It appears however that uterine rupture rate (complete or incomplete) is slightly higher in comparison to a previous caesarean at term, which might occur prematurely and before labour.

[Impact of the external cephalic version on the obstetrical prognosis in a team with a high success rate of vaginal delivery in breech presentation]. / Impact de la version par manœuvre externe sur le pronostic obstétrical dans une équipe à fort taux de réussite de l'accouchement vaginal du siège.

OBJECTIVES: To analyse the impact of external cephalic version (ECV) on caesarean section rate in a team with a high success rate of vaginal delivery in breech presentation. MATERIALS AND METHODS: Retrospective monocentric study including 298 patients with a breech presentations between 33 and 35weeks of amenorrhea followed at our university hospital and delivered after 35weeks, between 1st January 2011 and 31st December 2013. Patients were divided into 2 groups: planned ECV (n=216 patients) versus no planned ECV (n=57 patients). RESULTS: Our rate of successful vaginal breech delivery over the period of the study was 61.1%. We performed 165 ECV, with a 21.8% success rate. The average term of the attempt of ECV was 36.7weeks of amenorrhea. The caesarean section rate was not significantly different in the planned ECV group, even after adjustment on age, parity and previous caesarean delivery (adjusted OR=1.67 [0.77-3.61]). Attempt of ECV did not reduce the number of breech presentation at delivery (61.1% versus 61.4% [P=0.55]). CONCLUSION: Planned ECV in our center with a high level of breech vaginal delivery did not significantly impact our cesarean section rate.

Teriparatide in Fracture Non-Unions.

BACKGROUND: The use of teriparatide in the management of fracture disorders is poorly documented. This study aims to show that teriparatide administration may improve the healing process in patients with nonunions after open fixation of traumatic fractures of the lower limb. METHODS: Four patients received Teriparatide for management of non-unions after open fixation of traumatic fractures of the lower limb. RESULTS: Teriparatide administration resulted in adequate bone callus over the site of nonunion in all the patients, and clinical and radiographic evidence of sound union. CONCLUSIONS: The efficacy of teriparatide in delayed or non unions is still unclear. It may induce an angiogenetic response which counteracts the features responsible for development of non-union. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Impact of age on viral kinetics of peginterferon alfa-2a/ribavirin in chronic hepatitis C: final analysis from the PROPHESYS cohort.

The population of patients with chronic hepatitis C viral infection is ageing; however, elderly, hepatitis C-infected patients are understudied and less frequently treated. This subanalysis of data from the multinational PROPHESYS study examined associations between age (≤65 vs >65 years), on-treatment virological response and sustained virological response (SVR) in patients treated with peginterferon alfa-2a (40KD)/ribavirin in accordance with local licences. PROPHESYS comprised three cohorts studied in 19 countries according to country-specific legal and regulatory requirements. This subanalysis includes treatment-naive HCV mono-infected patients assigned to receive peginterferon alfa-2a (40KD)/ribavirin, with 6276 individuals aged ≤65 years and 349 aged >65 years. Rapid virological response (RVR) rates by Week 4 were consistently lower in older genotype (G) 1 (21.6% vs 27.2% in younger patients), G2 (80.7% vs 85.1%) and G3 (60.0% vs 74.2%) patients. SVR rates were significantly lower (29.8% vs 43.0%) and relapse rates significantly higher (43.1% vs 26.7%) in older G1 patients (P = 0.0002 vs ≤65 years). In contrast, SVR and relapse rates were similar in G2 and G3 patients regardless of age. The positive predictive value of RVR for SVR was comparable in older and younger G1 patients (66.7% vs 68.6%, respectively) and higher in older G2 (80.7% vs 75.6%) and G3 (77.8% vs 66.8%) patients. Virological response rates are generally lower in elderly CHC patients, and RVR is a reliable positive predictor of SVR in patients >65 years.

Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis.

AIMS: Sporadic inclusion body myositis (s-IBM) is characterized by rimmed vacuole formation and misfolded protein accumulation. Intracellular protein aggregates are cleared by autophagy. When autophagy is blocked aggregates accumulate, resulting in abnormal rimmed vacuole formation. This study investigated the autophagy-lysosome pathway contribution to rimmed vacuole accumulation. METHODS: Autophagy was studied in muscle biopsy specimens obtained from eleven s-IBM patients, one suspected hereditary IBM patient, nine patients with other inflammatory myopathies and nine non-myopathic patients as controls. The analysis employed morphometric methods applied to immunohistochemistry using the endosome marker Clathrin, essential proteins of the autophagic cascade such as AuTophaGy-related protein ATG5, splicing variants of microtubule-associated protein light chain 3a (LC3a) and LC3b, compared with Beclin 1, the major autophagy regulator of both the initiation phase and late endosome/lysosome fusion of the autophagy-lysosome pathway. RESULTS: In muscle biopsies of s-IBM patients, an increased expression of Clathrin, ATG5, LC3a, LC3b and Beclin 1 was shown. Moreover, the inflammatory components of the disease, essentially lymphocytes, were preferentially distributed around the Beclin 1(+) myofibres. These affected myofibres also showed a moderate sarcoplasmic accumulation of SMI-31(+) phospho-tau paired helical filaments. CONCLUSION: The overexpression of autophagy markers linked to the decreased clearance of misfolded proteins, including SMI-31, and rimmed vacuoles accumulation may exhaust cellular resources and lead to cell death.

Effect of autologous transplantation of bone marrow cells concentrated with the MarrowXpress system in patients with critical limb ischemia.

Critical limb ischemia (CLI), a vascular disease affecting lower limbs, with high morbidity and mortality, is becoming a challenge due to the aging of the population. Patients without direct revascularization options have the worst outcomes. To date, 25% to 40% of CLI patients are not candidates for surgical or endovascular approaches, facing a major amputation as the ultimate option. This study sought to assess the safety and efficacy of transplantation of autologous bone marrow concentrates in "no-option" patients to restore blood perfusion by collateral flow and limb salvage. We performed a nonrandomized, noncontrolled pilot study for no-option CLI patients using intra-arterial infusion of autologous bone marrow concentrate. Variation of blood perfusion parameters, evaluated by laser doppler flowmetry after 6 and 12 months, was set as primary endpoint. Thirteen enrolled patients showed improvements in objective measurements of perfusion. This uncontrolled study provided evidence that transplantation of autologous bone marrow concentrates was well tolerated by CLI patients without significant adverse effects, demonstrating improved perfusion, confirming the feasibility and safety of the procedure.

Percutaneous radiofrequency ablation of hepatocellular carcinoma compared to percutaneous ethanol injection in treatment of cirrhotic patients: an Italian randomized controlled trial.

AIM: To compare 5-year survival of patients with a single hepatocellular carcinoma≤3 cm randomly assigned to receive percutaneous ethanol injection or radiofrequency ablation. PATIENTS AND METHODS: A total of 285 patients (192 males, mean age 70 years), with a single hepatocellular carcinoma (mean diameter 2.2 cm) were randomly assigned to receive percutaneous ethanol injection (n=143) or radiofrequency ablation (n=142). The primary endpoint of the study was 5-year survival. RESULTS: Overall 143 patients underwent percutaneous ethanol injection and 128 radiofrequency ablation. In consideration of segmental location, in fact, 14 patients with 14 hepatocellular carcinomas could not be treated with established radiofrequency and were treated with percutaneous ethanol injection; these patients were not included in the survival evaluation. In the percutaneous ethanol injection and in the radiofrequency ablation groups, 3- and 5-year survival rates of 74% and 68%, and 78% and 68%, and 79% and 70% [corrected] respectively, were observed (p=n.s). In the percutaneous ethanol injection group, 3- and 5-year local recurrence rates were 9.4% and 12.8% respectively; in the radiofrequency group, the 3 and 5 years local recurrence rates were 7.8% and 11.7%, respectively (p=n.s.). The overall costs of percutaneous ethanol injection and radiofrequency ablation were 1359 Euros and 171.000 Euros, respectively (p<0.0001) CONCLUSION: Percutaneous ethanol injection and radiofrequency ablation conferred similar 5-year survival. Feasibility is not the same for both procedures. Percutaneous ethanol injection is much cheaper than radiofrequency ablation and should be considered whether in poor and rich countries.

Total knee arthroplasty for post-traumatic proximal tibial bone defect: three cases report.

Bone stock deficiency in primary as well as in revision total knee arthroplasty (TKA) represents a difficult problem to surgeon with regard to maintaining proper alignment of the implant components and in establishing a stable bone-implant interface. Different surgical procedures are available in these situations, for instances the use of bone cement, prosthetic augments, custom implant, and wire mesh with morsellized bone grafting and structural bone allograft. Structural allograft offers a numerous advantages as easy remodeling and felling cavitary or segmental defects, excellent biocompatibility, bone stock restoration and potential for ligamentous reattachment. In this article we report a short term result of three cases affected by severe segmental medial post/traumatic tibial plateau defect in arthritic knee, for which massive structural allograft reconstruction and primary total knee replacement were carried. The heights of the bone defect were between 27-33 mm and with moderate medio-lateral knee instability. Pre-operative AKS score in three cases was 30, 34 and 51 points consecutively and improved at the last follow-up to 83, 78 and 85 consecutively. No acute or chronic complication was observed. Last radiological exam referred no signs of prosthetic loosening, no secondary resorption of bone graft and well integrated graft to host bone. These results achieved in our similar three cases have confirmed that the structural bone allograft is a successful biological material to restore hemi-condylar segmental tibial bone defect when total knee replacement is indicated.

Pregnancy-induced symptomatic pelvic and extra-pelvic cavernous hemangiomatosis.

BACKGROUND: Pregnancy-induced pelvic and extra-pelvic cavernous hemangiomatosis is a serious condition, associated with considerable maternal and fetal risks. This report describes the ultrasound (US) features and the clinical management of such rare condition in a young caucasian woman. CASE: A 20-year-old woman was referred to our department following the occurrence of swelling in her inguinal and vulvar area together with lipotimic episodes. Diffuse cavernous hemangiomatosis of the pregnant uterus associated with vaginal, inguinal and vulvar varicosities was diagnosed clinically and by 2D and 3D US. The patient underwent expectant management of the gestation, under close US monitoring of both superficial and inner varicosities, careful surveillance of the maternal and fetal condition and prophylaxis for thrombotic complications with medical therapy. A cesarean section was performed at 37 weeks of gestation because of the worsening of her lipotimic episodes and her unfavorable Bishop's score. CONCLUSION: This is the first report in which pregnancy-induced varicose disease involved contemporarily uterine, vaginal, inguinal, and vulvar veins totally sparing the lower extremities. This case suggests that, under close monitoring, a conservative approach can be adopted in such conditions. Vaginal delivery is to be preferred, but if cesarean section is required, the surgery should be performed under general anesthesia and packed red cells and plasma units should always be available.

A novel insertional mutation in the prion protein gene: clinical and bio-molecular findings.

A young man, presenting with early onset of personality and behavioural changes followed by slowly progressive cognitive impairment associated with marked bi-parietal cerebral atrophy, was found to carry a novel seven extra-repeat insertional mutation in the prion protein gene (PRNP). In vitro, the mutated recombinant prion protein (PrP) showed biochemical properties that were consistent with pathological PrP variants. Our results further underline the heterogeneity of neurological pictures associated with insertional mutations of PRNP, indicating the diagnostic difficulties of sporadic cases with early-onset atypical dementia.

Frequency of headaches in patients over 80. A preliminary report.

We evaluated 44 old patients (mean age 84 years) in order to study the frequency of headaches. The frequency found in our sample is higher in comparison to other studies. Further studies including a larger number of patients are needed to obtain more incisive results.