Questionnaire and tools: clinical powerful instrument in acromegaly diagnosis and management.

PURPOSE: Acromegaly is a rare chronic disease characterized by systemic comorbidity and reduced quality of life. Although achieving biochemical control has always been the primary goal of acromegaly therapy, recent evidence has shown that the traditional assessment does not adequately capture the complexity of symptoms and patients' perception. These findings result in the need to improve a fast decision-making process of the clinician, who should not only take into account biochemical-instrumental criteria, but also patients' symptoms. With the aim of supporting the clinician in the diagnostic and therapeutic decision-making process several disease-specific tools have been developed. The aim of this review is to provide a description of the acromegaly-specific tools, presenting their main features, their application in daily practice, and their efficacy and utility. METHODS: A systematic search of Medline/PubMed, ISI-Web of Knowledge, and Google Scholar databases was done. RESULTS: Specific instruments and questionnaires have recently been developed to assist clinicians in the assessment of acromegaly. These are either Patient-Reported Outcome tools, such as Acromegaly Quality of Life Questionnaire (AcroQoL) and Pain Assessment Acromegaly Symptom Questionnaire (PASQ), or Clinician-Reported Outcome tools, such as ACROSCORE, SAGIT® and Acromegaly Disease Activity Tool (ACRODAT®). Such tools are extremely flexible and, therefore, have been widely adopted by endocrinologists and other professionals, so much so that they have also been included as recommendations in the 2018 international guidelines. CONCLUSION: Questionnaires and tools are useful in the management of acromegaly patients. They help clinicians evaluate patients' symptoms and could assist in the evaluation of disease activity.

Posterior cruciate ligament reconstruction in skeletally immature athletes.

Posterior cruciate ligament rupture is a rare knee ligamentous injury in skeletally immature patients with unfused growth plates. Despite being very uncommon, it still represents a significant challenge in terms of decision-making and treatment choice. The purpose of this case series was to report subject and objective outcomes (IKDC, TAS,LYSHOLM,KT2000) after PCL reconstruction in two teenage elite football players aged 15 and 16 respectively, who underwent surgical repair in July 2017 using for the femoral and tibial fixation of the PCL graft (hamstring tendons) respectively a curve cross-pin system and interferential screw. At fifteen months follow up, both athletes had returned to normal, pre-injury, competing levels with no leg discrepancy.

Modular dual mobility cups with multihole metal back in total hip arthroplasty revision: a systematic review.

Dislocation after hip revision is a frequent complication; amongst the strategies to prevent dislocation dual mobility (DM) implants are gaining popularity. We want to evaluate the reliability of non cemented DM cups with multihole metal back and chrome-cobalt liner called Modular Dual Mobility (MDM). We performed a systematic review and selected 5 studies with a total of 285 hips who underwent revision surgery with MDM implants. The mean survivorship rate of the 5 studies was 92.46% (range 90-96%). 267 prosthesis (93.6%) were still implanted at the last follow-up; the mean weighted follow up was 38.7% (range 24-48). We found 13 mechanical complications in 285 hips (4.5%). Five of them were treated conservatively; the other 8 were treated with re-revision. Nine of these complications were dislocation and recurrent instability; 2 of them were associated to metallosis and adverse local tissue reaction. There was 1 patient that had episodes of subluxation; 2 cases of impingement and 1 case of metallosis. Zero intraprosthetic dislocations (IPD) occurred in 285 hips. A 93.6% survivorship is a good result for MDM implants, considering that most of patients had important bone loss and went through multiple revisions. The rate of dislocation is very low compared to the mean rate of dislocation in revision hip surgery. In our review, fretting is a rare complication but it can lead to ALTR and metallosis. For this reason, MDM implants have to be used in selected cases at high risk of dislocation. In conclusion MDM is a great option for decreasing dislocation rate in hip revision, but a longer follow-up and a greater number of cases is needed to assess its reliability.

FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus.

The forkhead, Fox, gene family comprises a diverse group of 'winged-helix' transcription factors that play important roles in development, metabolism, cancer and aging. Recently, several forkhead genes have been demonstrated to play critical roles in lymphocyte development and effector functions. Alterations of the FOXN1 gene in both mice and humans result in a severe combined immunodeficiency caused by an intrinsic defect of the thymus associated with congenital alopecia (Nude/severe combined immunodeficiency phenotype). FOXN1 is a member of the class of proteins involved in the development and differentiation of the central nervous system. We identified a human fetus homozygous for a mutation in FOXN1 gene who lacked the thymus and also had abnormal skin, anencephaly and spina bifida. Moreover, we found that FOXN1 gene is expressed in mouse developing choroid plexus. These observations suggest that FOXN1 may be involved in neurulation in humans.

Distinct mechanisms of form-from-motion perception in human extrastriate cortex.

The exquisite sensitivity of the human visual system to form-from-motion (FfM) cues is well documented. However, identifying the neural correlates of this sensitivity has proven difficult, particularly determining the respective contributions of different motion areas in extrastriate visual cortex. Here we measured visual FfM perception and more elementary visual motion (VM) perception in a group of 32 patients suffering from acute posterior brain damage, and performed MRI-based lesion analysis. Our results suggest that severe FfM perception deficits without an associated deficit of VM perception are due to damage to ventral occipito-temporal cortex (VOT), whereas associated deficits of FfM and VM perception are due to damage either in proximity to area MT+/V5 or an area including lateral occipital complex (LOC) and VOT. These data suggest the existence of at least three functionally and anatomically distinct regions in human visual cortex that process FfM signals.

Hepatitis B reactivation in patients with chronic hepatitis C undergoing anti-viral therapy with an interferon-free regimen.

BACKGROUND: A few cases of hepatitis B virus (HBV) reactivation during anti-viral therapy against hepatitis C (HCV) have been reported. However, the information regarding the real impact of this phenomenon is scarce. AIM: To evaluate the risk of HBV reactivation during anti-viral therapy against HCV with an interferon-free regimen with direct-acting anti-virals (DAAs). METHODS: Observational and prospective study of 352 patients receiving DAAs therapy between September 2015 and May 2016. HBV-DNA and ALT levels were monitored at baseline, at week 4 of anti-viral therapy, at end of treatment and 12 weeks after treatment discontinuation in patients with HBV surface antigen (HBsAg) positive or HBV core antibody (anti-HBc) positive before starting anti-viral therapy. RESULTS: Ten (2.8%) and 64 (18%) patients were HBsAg and anti-HBc positive at baseline, respectively. Five (50%) of 10 HBsAg positive and one (1.6%) of 64 anti-HBc positive patients presented HBV virological reactivation (>1log increase in HBV-DNA levels). None of these patients presented clinical reactivation (increase in ALT levels). CONCLUSIONS: HBV virological reactivation is frequent in HBsAg+ patients receiving anti-viral therapy against HCV. However, HBV-DNA elevations were modest (<20 000 IU/mL) and without clinical impact (no ALT elevation).

Allogeneic bone marrow transplantation restores IGF-I production and linear growth in a gamma-SCID patient with abnormal growth hormone receptor signaling.

Severe combined immunodeficiency (SCID) is a heterogeneous group of disorders characterized by a severe defect of both T- and B-cell immunity, which generally require allogeneic bone marrow transplantation (BMT) within the first years of life. We previously reported a patient affected with an X-linked SCID due to L183S hemizygous missense gamma chain mutation, whose severe short stature was due to a peripheral growth hormone (GH) hyporesponsiveness associated to abnormal GH receptor (GH-R) signal transduction. In this study, we report the effect of BMT on the GH-R/insulin-like growth factor I (IGF-I) axis. After BMT, the patient showed a significant improvement in linear growth and normalization of basal- and GH-stimulated IGF-I values, which paralleled a fully competent immunological reconstitution. This suggests that cells derived from the hematopoietic stem cell may exert an unexpectedly significant role in producing IGF-I. This may also suggest that stem cell-based therapies may be useful for the correction of non-hematopoietic inherited disorders, such as those of GH-R/IGF-I axis.

Distinct short-term memory systems for sound content and sound localization.

Short-term memory for sound content and sound localization was investigated in normal subjects using the same/different comparison of two sound stimuli separated by an interval. Auditory or visual interference tasks requiring recognition or spatial judgements were introduced in the interval. Auditory interference tasks reduced memory for sound content and sound location in a specific way. Memory for sound content was significantly more reduced by auditory recognition than by auditory spatial interference task. Visual interference tasks reduced significantly memory for sound location but not for sound content. These results suggest that (i) short-term memory for sound content and that for sound location involve partially distinct processing; and (ii) auditory spatial functions are more closely linked to visual functions than auditory recognition.

Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population.

Genetic alterations of the FOXN1 transcription factor, selectively expressed in thymic epithelia and skin, are responsible in both mice and humans for the Nude/SCID phenotype. The first described human FOXN1 mutation was a C792T transition in exon 5 resulting in the nonsense mutation R255X, and was detected in two probands originated from a small community in southern Italy. In this community, four additional children affected with congenital alopecia died in early childhood because of severe infections. In this study, we report on the screening for this mutation in 30% of the village population. This analysis led us to identify 55 heterozygous carriers (6.52%) of the R255X mutation out of 843 inhabitants screened. A genealogical study revealed that these subjects, belonging to 39 families, were linked in an extended 7-generational pedigree comprising 483 individuals. Through the archival database a single ancestral couple, born at the beginning of the 19th century, was identified. To confirm the ancestral origin of the mutation we genotyped two microsatellite markers, D17S2187 and D17S1880, flanking the FOXN1 gene on chromosome 17. The three haplotypes identified, 3/R255X/3, 3/R255X/2 and 3/R255X/1, are consistent with a single ancestral origin for the mutation R255X.

Distinct pathways involved in sound recognition and localization: a human fMRI study.

Evidence from psychophysical studies in normal and brain-damaged subjects suggests that auditory information relevant to recognition and localization are processed by distinct neuronal populations. We report here on anatomical segregation of these populations. Brain activation associated with performance in sound identification and localization was investigated in 18 normal subjects using fMRI. Three conditions were used: (i) comparison of spatial stimuli simulated with interaural time differences; (ii) identification of environmental sounds; and (iii) rest. Conditions (i) and (ii) required acknowledgment of predefined targets by pressing a button. After coregistering, images were normalized and smoothed. Activation patterns were analyzed using SPM99 for individual subjects and for the whole group. Sound recognition and localization activated, as compared to rest, inferior colliculus, medial geniculate body, Heschl gyrus, and parts of the temporal, parietal, and frontal convexity bilaterally. The activation pattern on the fronto-temporo-parietal convexity differed in the two conditions. Middle temporal gyrus and precuneus bilaterally and the posterior part of left inferior frontal gyrus were more activated by recognition than by localization. Lower part of inferior parietal lobule and posterior parts of middle and inferior frontal gyri were more activated, bilaterally, by localization than by recognition. Regions selectively activated by sound recognition, but not those selectively activated by localization, were significantly larger in women. Passive listening paradigm revealed segregated pathways on superior temporal gyrus and inferior parietal lobule. Thus, anatomically distinct networks are involved in sound recognition and sound localization.