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Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Vascular stress at the level of the uterus-placental unit, with chronic placental ischemia, results in intrauterine growth restriction. Expectation management can be used, when the situation allows, in cases of compensated intrauterine growth restriction. The aim of the present study was to evaluate the neonatal prognosis of preterm births with and without growth restriction and term births with growth restriction in order to improve decisional accuracy regarding the termination of pregnancy. The frequency of term birth infants with low birth weight for gestational age was ~2%. The male sex, predominated only in the group of premature infants with normal weight for the gestational age. The highest frequency of neonatal complications studied occurred in the group of preterm neonates small for gestational age (SGA) with statistical significance obtained for cardiovascular arrest acute respiratory failure, ulcer-necrotic enterocolitis, respiratory distress, cerebral edema, intraventricular hemorrhage, cerebral hemorrhage, pulmonary hemorrhage, neonatal infection, hypoglycemia, retinopathy, anemia, hemorrhagic disease, disseminated intravascular coagulation, disease of hyaline membranes, neonatal sepsis, need for intensive neonatal therapy and death. In conclusion, immediate neonatal adaptation of SGA preterm neonates is more deficient than for preterm neonates with appropriate weight for gestational age; the adaptation of preterm neonates, in turn, is more deficient than term newborns with intrauterine growth restriction. The term newborns with intrauterine growth restriction have a neonatal adaptation comparable to that of the term newborns with weight corresponding to the gestational age.

Introduction. The concept of underactive bladder is relatively new. Currently there is no generally accepted definition of this pathology. Diagnosis depends on urodynamic findings, and symptoms are usually rare and intricated with the symptoms of other urinary pathology. Matherials and methods. This review examines the current literature on underactive bladder regarding pathology, definition, diagnosis, current guidelines, and any further potential medical developments. Conclusions. Underactive bladder is a poorly understood pathologic condition. Only since 2002 has there been any consensus regarding the definition. The diagnosis relies only on urodynamics; clinical diagnosis is a challenge even for a consultant; and treatment does not seem to alleviate much of the suffering. This disease remains underrecognized and undertreated. More research is needed to identify less invasive diagnosis tools and treatment for this pathology.

The retroperitoneum can host a wide variety of pathologies, including benign and malignant tumors. Primary retroperitoneal tumors are rare, usually large in size, more than half of them being larger than 20 cm at the time of diagnosis, due to their silent growth. They often present several therapeutic challenges because of their rarity, relatively late presentation and anatomical location, often in close relationship with several important structures in the retroperitoneal space. Extensive surgery is often required because of the intimate relationships with vital organs in the retroperitoneum. Retroperitoneal sarcomas frequently involve major vessels, originating from them or secondarily encase or invade them, requiring major vascular resections, with increasing morbidity. The main intervention that can increase the survival of patients with retroperitoneal tumors is radical resection. The involvement of large retroperitoneal vessels often makes impossible a radical intervention, usually because of the lack of an adequate material for ample and laborious vascular reconstruction. In this paper, a thorough search of the PubMed database was performed, to bring into the light the implications of vascular involvement in primary retroperitoneal tumors and the need of a strong cooperation between the urological or general surgeon and the vascular surgeon.

The traumatic or surgical amputation of the forearm or of the hand is a challenging interdisciplinary domain, requiring the collaboration of surgeons, engineers, prostheticians, clinical pharmacology experts in chronic pain management, exoprosthesis manufacturing companies, social workers and last but not least the patient himself/herself. There are a relative few methods of surgical preparation of the amputation stump for use use an external prosthesis. Most of these techniques do not provide a sufficient number of electrical sEMG signals for the efficient control of a modern myoelectric exoprosthesis. We present the surgical aspects and anesthesio-pharmacological implications of the practical study into the applicability of the concept of myoplastic transposition through a forearm fascia breach. We present the data and we discuss the results of sEMG signal acquisition, both before and after the procedure, and we conclude regarding the potential of the method as a means of improving the current standard surgical technique.

This prospective study aimed to determine the manometric pattern and the prevalence of esophageal dysmotility in 79 morbidly obese patients selected for laparoscopic sleeve gastrectomy. After clinical evaluation and upper gastrointestinal endoscopy, high-resolution esophageal manometry was performed. The esophageal peristalsis, lower esophageal sphincter (LES) basal pressure, and LES relaxation were evaluated. Demographic data showed a predominance of females (55.70%) and both females and males were in the 5(th) decade of life. In addition, approximately 3/4 of the patients (78.48%) were from the urban zone. The mean body mass index of the patients was 46.40±6.0069 kg/m(2), with a maximum of 61 kg/m(2). The LES basal pressure was normal in 59.49% of the patients, with a mean value of 31.40±18.43 mmHg. LES basal hypertonia was observed in 26.58%, and LES hypotonia in 13.93% of patients; 46.84% (37 patients) had abnormal manometric findings: 24.05% (19 patients) had EGJ outflow obstruction, 12.66% (10 patients) ineffective esophageal motility, 3.8% (3 patients) distal esophageal spasm, 3.8% (3 patients) Jackhammer esophagus, 2 cases were suggestive for type 2 achalasia but in asymptomatic patients. Ineffective esophageal motility was not associated with diabetes mellitus type 2 or erosive esophagitis according to our data. Hiatal hernia (HH) was manometrically diagnosed in 23 patients (29.11%). Preoperative high-resolution esophageal manometry in obese patients demonstrated a high prevalence of motility disorders, but in asymptomatic patients, thus in the future, we require more studies and larger cohorts to better appreciate the clinical impact.

The immune system is dysfunctional in cancer, and therapeutic approaches designated to restore immunity and increase long-term overall survival are desirable. The role of immunotherapy is to trigger the immune system to recognize and destroy tumor cells. Interleukin-15 (IL-15) is a member of the common gamma-chain (γc) cytokines that promote the differentiation and expansion of T cells, B cells and natural killer (NK) cells, leading to enhanced antitumor responses. This suggests that IL-15 is a promising candidate for anticancer therapy. Renewed interest in cancer immunotherapy has led to an increased number of preclinical studies and clinical trials that have investigated the reliability and potency of IL-15-based agents, not only as single therapy, but also in combination with others. This review provides a description of these studies which show the advantages and disadvantages of IL-15 as an immunotherapeutic agent. We present here the role of IL-15 and pharmacologically improved IL-15 superagonists as a single treatment or in combination with other therapeutic agents.

SARS-CoV-2 infections raise many practical concerns in a woman with multiple sclerosis (MS) during the perinatal period. On the other hand, the impact of COVID-19 on patients with MS and disease-modifying therapies (DMTs) is unknown. We report on a female patient who was treated with interferon beta 1a (IFNB-1a) for many years for relapsing-remitting multiple sclerosis (RRMS) until December 2018. She developed COVID 19 infection in April 2020, after giving birth to a healthy baby girl, five weeks before. She developed a mild right hemiparesis 2 weeks later, without cold symptoms. On admission, PCR for SARS-CoV-2 was positive, and she received antivirals and corticotherapy. One month later, specific IgG and IgM antibodies were negative. The patient did not develop immunity to COVID-19 infection. This report raises several problems. The focal deficit could be a real relapse or a pseudo-relapse due to SARS-CoV-2 and postpartum patient vulnerability. The treatment options in this particular case raise many challenges. The absence of antibodies after a SARS-CoV-2 infection raises a big question over the acquired immunity, the increased risk of reinfection, and the subsequent evolution of MS. The standard of care for a woman with MS and COVID-19 infection during the postpartum period must be explored and more precise recommendations must be established in the future.

Medical research continues to focus on developing specific treatment strategies, including biological products that are effective and have a good safety profile. Due to their novelty, an updated overall view is offered on some neurological diseases which benefit from monoclonal antibodies (mAbs), for better treatment in clinical decisions. An extensive literature review was performed using PubMed with the following search terms: ‘monoclonal antibodies’ and ‘history of monoclonal antibodies’ and ‘monoclonal antibodies in neurology’. The following information was collected: the era before the discoveries of mAbs, the stage of implementation of biotechnologies for mAbs, and the clinical trials submitted at https://clinicaltrials.gov/ with patients suffering from neurological diseases treated with mAbs. Since 2004, mAbs have been used to treat several neurological diseases, yielding new therapeutic perspectives: natalizumab, alemtuzumab and ocrelizumab for multiple sclerosis, eculizumab for myasthenia gravis, erenumab and frenazumab for migraine, galcanezumab for migraine and cluster headache, eculizumab for neuromyelitis optica spectrum disorder. As in other cases, drug repurposing is applied to monoclonal antibodies, saving time and money. These innovative therapies are more effective and can treat previously untreatable diseases. As better understanding of the pathogenic mechanisms of neurological diseases is gained, additional mAbs are expected to be developed at a lower cost and with better safety profile compared with current treatment options.

Non-alcoholic fatty liver disease (NAFLD) is a component of metabolic syndrome that significantly increases the cardiovascular risk of patients with glucose metabolism alterations. This study identified the prevalence of NAFLD, predictors of NAFLD and explored the link between insulin sensitivity, insulin resistance and leptinemia in 143 patients registered with prediabetes. Abdominal ultrasound was performed, and fasting insulin, postprandial insulin, leptin levels, common clinical/biochemical determinations were assessed. Certain variables that can predict NAFLD existence were determined and it was found that there is a high prevalence of NAFLD in patients with prediabetes. In univariate analysis, statistically significant associations (P

The role of interferon β-1b (IFNβ-1b), used for multiple sclerosis (MS) therapy, in cancer occurrence is uncertain. There is evidence supporting the role of human herpesvirus 4 [Epstein-Barr virus (EBV)] in thyroid cancer and MS. Simultaneous occurrence of papillary and medullary carcinomas is rare, and its association with MS in a young woman raises questions. A 46-year-old female patient was diagnosed with relapsing-remitting multiple sclerosis in 2008. In 2018, cervical MRI detected a thyroid nodule with right cervical adenopathy. Her thyroid function was normal, but increased calcitonin levels were found (70.53 pg/ml; normal value

Arthroplasty of the hip, for either arthritic changes or femoral neck fracture, is a common procedure in orthopedic surgery. Although the standard designs for implantation, either cemented or uncemented, are well described and studied, there are also alternative designs regarding the implantation of both prosthetic stem and cup. This paper aims to explore one such alternative design, using the screw-in technique. It has been described in past literature for uncemented fixation of both the cup and the stem, and the biomechanical principles of fixation are different from the classical methods, offering certain advantages that are insufficiently explored in current-day endoprosthesis. Also, we will be presenting an innovative femoral stem design, recently developed, that combines an uncemented screw-on technique with a cemented augmentation possibility, aimed to provide the practitioner with the advantages of a bone-preserving mini-stem design, combined with the innovative screw-in fixation technique and the versatility of the hybrid cemented/uncemented fixation method.

Minimally invasive biopsy procedures have proven over the years to be essential for obtaining a correct diagnosis of retroperitoneal tumors, that allows proper therapeutical conduct. These procedures offer valuable tissue fragments for histopathological examination, that permits the distinction between benign and malignant tumors, identifying the tumors that can benefit from neo-adjuvant treatments, such as chemotherapy or radiotherapy and those that have a direct surgical indication. We have searched the existing data regarding minimally invasive biopsy in retroperitoneal tumors using the PubMed database, in order to evaluate the role of this procedure in establishing a correct diagnosis, as well as to find out the risks of tumor cell seeding and local recurrence after needle biopsy. The risk of tumor cell seeding is very low (

Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians.

Infections are an ever-present problem in the medical community, even more so for patients with multiple sclerosis (MS), for whom these infections have been linked to relapses and neurological disabilities. Even though it was believed that MS can be caused by an infection, research does not support this theory. MS is a chronic inflammatory disease considered to be autoimmune. Vaccination is proven to be one of the most effective means to prevent infections, but still it is surrounded by controversy in the general populations, as well as in the MS group. Vaccines are generally considered safe for MS patients. The exceptions from this, which turn into contraindications, are a medical history of allergic reactions to one of the vaccine components and immunosuppressed patients in the particular case of live vaccines. Given the presumed autoimmunity of the disease, some medication for MS is immunosuppressive and any live vaccine should be administered before starting treatment. Although there is still confusion regarding this subject, the current guidelines have clearer recommendations about vaccinations in MS patients and especially in treated MS patients.

Multiple sclerosis, demyelinating, inflammatory, degenerative, and chronic disease, raises many challenges in terms of disease management. The autonomic nervous system is affected by neuroinflammation but also contributes to its maintenance and the evolution of the disease. Multiple sclerosis interfering with parasympathetic or sympathetic modulation may influence the immune response. Less attention is paid to autonomic dysfunctions, although they produce a serious impact on the quality of life. In addition to motor disabilities, patients also have non-motor dysfunctions. Regardless of its clinical forms, patients with multiple sclerosis may have autonomous disturbances such as bladder, sexual, cardiovascular, thermoregulatory, gastrointestinal dysfunction and fatigue. These must be identified based on medical history, clinical symptoms, and specific paraclinical tests. In addition to the multitude of immunomodulatory therapeutic agents that influence the progression of the disease, the therapy of autonomic dysfunctions remains difficult to address. However, their identification and treatment lead to increased quality of patient management and avoid complications of this disease.

Retroperitoneal tumors, once considered uncommon, have been reported in the last years in such numbers that they cannot be considered anymore a rare condition. Tumor recurrence following surgical excision is quite common and a tumor that was considered originally as benign in many cases can recur as a malignant tumor. The purpose of this paper is to underline the difficulties in terms of establishing a correct diagnosis and a proper therapeutic protocol when facing a retroperitoneal mass of unknown origin, as well as to present the available data regarding prognosis, treatment options and tumor recurrence. Retroperitoneal tumors can be classified as benign or malignant; solid, cystic or both; single or multiple, and of varied histological types. A high percentage of patients with retroperitoneal tumors are discovered in advanced stages, usually seeking medical help for symptoms related to nearby organ compression/invasion. This pathology requires a prompt and adequate multidisciplinary management, in order to achieve disease control and to reduce the recurrence rate. Complete surgical resection is the potential curative treatment for retroperitoneal tumors and it is best managed in high-volume centers, by a multidisciplinary team. Complete oncological tumor resection and tumor grade remain the most important predictors for local recurrence and disease-specific survival. Further research is required in order to define the role of radiotherapy, as well as to discover new biological therapies that target various molecular pathways involved in retroperitoneal cancers.

Venous graft failure is a complex pathology of surgical revascularization that comprises many physiopathologic mechanisms, some of them still unclear until the present moment. Arterialization of the venous graft produces structural modifications in the graft wall, including all anatomic layers: intima, media, and adventitia. Of these, the most important aspect of graft dysfunction is intimal destructuration by various mechanisms: endothelial cell separation and cell loss, intimal edema, exposed basement membrane, subendothelial collagen and elastin, intimal tears and flaps, fibrointimal hyperplasia, neointimal hyperplasia, and thrombus formation. Some of these pathogenic processes are exacerbated while others are diminished, but, overall, they lead to graft restenosis. Intimal edema extends toward the superjacent layer, producing myocite necrosis, fibrosis, and eventually aneurysm formation. Adventitial ischemia produced by graft harvesting determines vasa vasorum loss and vein sclerosis. Under these circumstances, neoangiogenesis occurs without oxygenation importance criteria, which leads to augmentation of neointimal hyperplasia and intimal and medial fibrosis. Therefore, graft restenosis is a complex process with many pathologic mechanisms, in general without sequentiality, but which taken together lead toward what is designated as “venous graft disease.”

Reno-ureteral lithiasis is a common pathology especially in socio-economically developed countries and may pose serious problems with renal function impairment. Urology is currently one of the surgical branches that benefit from a wide range of therapeutic options in reno-ureteral lithiasis, that revolutionized the criteria and indications of the lithiasis pathology, increasing the success rate and decreasing the number of days of hospitalization but which cannot provide satisfactory results if not complemented by imaging examinations. Non-contrast computer tomography is a key element in determining the best method of treatment by measuring the density of stones and increasing the stone-free rate of patients. Measurement of the stones density is done by Hounsfield units (HU), and patients who have had a [500 HU density have pleaded in over 90% for the uric acid composition. We included in our study a batch of 364 patients with reno-ureteral lithiasis and the treatment method was chosen based on the density of the stones: 64.83% of the patients with a density between 200-700 HU performed semi-rigid ureteroscopy and ballistic lithotripsy, 3.57% of patients with density between 700-1000 HU benefited from flexible ureteroscopy and laser lithotripsy, 17.58% of patients with density between 400-700HU performed ESWL and 13.73% with density]1000 HU have benefited from PCNL.

Pelvic organ prolapse (POP) is the aberrant herniation or descent of the pelvic units from their regular sites or their normal location in the pelvis. The pelvic organs that may be interested include the vaginal apex or uterus, anterior wall of vagina-cystocele, or posterior wall of vagina-rectocele. A thorough review of the literature using PUB med and SCOPUS databases was conducted We focused on those patients with preoperatory renal failure and on the results that these patients have achieved after surgery regarding this rare complication of pelvic prolapse. Pelvic organ prolapse can be considered an underdiagnosed disease. Many patients fail to present themselves to a doctor due to a false shame feeling. Fortunately renal failure is a rare complication of pelvic organ prolapse, often occurring in patients with asymptomatic or neglected POP. A major proportion of cases are able to recover some of their renal function but for some dialysis remains the only option.