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Isolated distal fibula fractures represent the majority of ankle fractures. These fractures are often the result of a low-energy trauma with external rotation and supination mechanism. Diagnosis is based on clinical signs and radiographic exam. Stress X-rays have a role in detecting associated mortise instability. Management depends on fracture type, displacement and associated ankle instability. For simple, minimally displaced fractures without ankle instability, conservative treatment leads to excellent results. Conservative treatment must also be considered in overaged unhealthy patients, even in unstable fractures. Surgical treatment is indicated when fracture or ankle instability are present, with several techniques described. Outcome is excellent in most cases. Complications regarding wound healing are frequent, especially with plate fixation, whereas other complications are uncommon.

Leukemia is a rare disease associated with a high mortality rate. The presence of unilateral or bilateral serous retinal detachment (SRD) as a sign of choroidal infiltration can be one of the manifestations of acute leukemia, both as a primary sign or in a relapse. We consolidated the literature on SRD as a sign of leukemic choroidopathy regarding its epidemiology, clinical manifestations, and main imaging diagnostic tools. Well-documented cases regarding acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), relapsed ALL and relapsed AML published until September, 2020, in peer reviewed journals were included. The literature shows an interesting range of choroidal infiltration cases assessed by modern imaging techniques, such as optical coherence tomography (OCT) with and without enhanced depth imaging (EDI) and fluorescein angiography (FA). These tools allow choroidal assessment and better understanding and characterization of this rare condition. Complete ophthalmological workup should be performed in these patients using both FA and EDI-OCT to assess the choroidal anatomy and integrity. An increase in choroidal thickness measured with EDI-OCT can reveal active disease and potentially diagnose a leukemic relapse promptly.

Background: From February 21, the day of hospitalisation in ICU of the first diagnosed case of Covid-19, the social situation and the hospitals’ organisation throughout Italy dramatically changed. Methods: The CIO (Club Italiano dell’Osteosintesi) is an Italian society devoted to the study of traumatology that counts members spread in public and private hospitals throughout the country. Fifteen members of the CIO, Chairmen of 15 Orthopaedic and Trauma Units of level 1 or 2 trauma centres in Italy, have been involved in the study. They were asked to record data about surgical, outpatients clinics and ER activity from the 23rd of February to the 4th of April 2020. The data collected were compared with the data of the same timeframe of the previous year (2019). Results: Comparing with last year, overall outpatient activity reduced up to 75%, overall Emergency Room (ER) trauma consultations up to 71%, elective surgical activity reduced up to 100% within two weeks and trauma surgery excluding femoral neck fractures up to 50%. The surgical treatment of femoral neck fractures showed a stable reduction from 15 to 20% without a significant variation during the timeframe. Conclusions: Covid-19 outbreak showed a tremendous impact on all orthopaedic trauma activities throughout the country except for the surgical treatment of femoral neck fractures, which, although reduced, did not change in percentage within the analysed timeframe.

Background This study was designed to demonstrate the non-inferiority (NI) in overall survival (OS) of suspension of androgen deprivation therapy (ADT) versus maintenance and intermittent versus continuous docetaxel administration in metastatic castration-resistant prostate cancer (mCRPC) patients. Patients and methods mCRPC patients were randomised to first-line docetaxel with maintenance or suspension of ADT. Patients attaining a prostate-specific antigen (PSA) response after four chemotherapy cycles underwent second randomisation to receive continuous or intermittent docetaxel therapy. Six hundred patients were to be randomised to achieve 80% statistical power to demonstrate an NI hazard ratio (HR) of 1.25 of interruption versus maintenance of ADT. Results The trial was prematurely closed when 198 participants were randomised. OS was similar in patients who continued (N = 96) versus those who interrupted (n = 102) ADT during docetaxel therapy (HR 0.98, 95% confidence interval [CI] 0.72–1.33] and those on a continuous (N = 35) versus an intermittent (N = 42) docetaxel schedule (HR 0.86, 95% CI 0.55–1.43). No difference in radiological progression-free survival, PSA response, or toxicity was observed between the study arms. The actual NI hazard margins of OS in Arms A and B patients were 1.33 and 1.43, respectively. Conclusions This trial enrolled one-third of the planned patients; this main weakness dramatically limits the interpretation of the results. ADT discontinuation and switching to an intermittent schedule did not seem to affect docetaxel efficacy. The absence of testosterone recovery in the majority of patients could have been a contributory factor. In men with mCRPC, ADT discontinuation should only be done with regular biochemical and clinical monitoring, with the option of quickly restarting ADT at disease progression.

Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events, but their effects on atherosclerotic plaque remain elusive. Using serial magnetic resonance imaging (MRI), we studied changes in carotid plaque lipid content and neovasculature under PCSK9 inhibition with alirocumab. Methods Among patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl but ineligible for high-dose statin therapy, those with lipid core on carotid MRI were identified to receive alirocumab 150 mg every 2 weeks. Follow-up MRI was performed at 3, 6, and 12 months after treatment. Pre- and post-contrast MRI were acquired to measure percent lipid core volume (% lipid core). Dynamic contrast-enhanced MRI was acquired to measure the extravasation rate of gadolinium contrast (Ktrans), a marker of plaque neovasculature. Results Of 31 patients enrolled, 27 completed the study (mean age: 69 ± 9; male: 67%). From 9.8% at baseline, % lipid core was progressively reduced to 8.4% at 3 months, 7.5% at 6 months, and 7.2% at 12 months (p = 0.014 for trend), which was accompanied by a progressive increase in % fibrous tissue (p = 0.009) but not % calcification (p = 0.35). Ktrans was not reduced until 12 months (from 0.069 ± 0.019 min−1 to 0.058 ± 0.020 min−1; p = 0.029). Lumen and wall areas did not change significantly during the study period. Conclusions Regression in plaque composition and neovasculature were observed under PCSK9 inhibition on carotid MRI, which provides unique insight into the biological process of plaque stabilization with disease-modifying therapies.

Purpose To report the anatomic and functional outcomes of autologous retinal transplantation (ART). Design Multicenter, retrospective, interventional, consecutive case series. Participants One hundred thirty eyes of 130 patients undergoing ART for the repair of primary and refractory macular holes (MHs), as well as combined MH-rhegmatogenous retinal detachment (MH-RRD), between January 2017 and December 2019. Methods All patients underwent pars plana vitrectomy and ART, with surgeon modification of intraoperative variables. A large array of preoperative, intraoperative, and postoperative data was collected. Two masked reviewers graded OCT images. Multivariate statistical analysis and subgroup analysis were performed. Main Outcome Measures Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. Results One hundred thirty ART surgeries were performed by 33 vitreoretinal surgeons worldwide. Patient demographics were: mean age of 63 ± 6.3 years, 58% female, 41% White, 23% Black, 19% Asian, and 17% Latino. Preoperative VA was 1.37 ± 0.12 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/500), which improved significantly to 1.05 ± 0.09 logMAR (Snellen equivalent, approximately 20/225; P Conclusions In this global experience, patients undergoing ART for large primary and refractory MHs and MH-RRDs achieved good anatomic and functional outcomes, with low complication rates despite complex surgical pathologic features.

Background Prehospital plasma transfusion in trauma reduces mortality. However, the underlying mechanism remains unclear. Reduction in shock severity may play a role. Lactate correlates with physiologic shock severity and mortality after injury. Our objective was to determine if prehospital plasma reduces lactate and if this contributes to the mortality benefit of plasma. Methods Patients in the Prehospital Air Medical Plasma trial in the upper quartile of injury severity (Injury Severity Score, >30) were included to capture severe shock. Trial patients were randomized to prehospital plasma or standard care resuscitation (crystalloid ± packed red blood cells). Regression determined the associations between admission lactate, 30-day mortality, and plasma while adjusting for demographics, prehospital crystalloid, time, mechanism, and injury characteristics. Causal mediation analysis determined what proportion of the effect of plasma on mortality is mediated by lactate reduction. Results A total of 125 patients were included. The plasma group had a lower adjusted admission lactate than standard of care group (coefficient, -1.64; 95% confidence interval [CI], -2.96 to -0.31; p = 0.02). Plasma was associated with lower odds of 30-day mortality (odds ratio [OR], 0.27; 95% CI, 0.08-0.90; p = 0.03). When adding lactate to this model, the effect of plasma on 30-day mortality was no longer significant (OR, 0.36; 95% CI, 0.07-1.88; p = 0.23), while lactate was associated with mortality (OR, 1.74 per 1 mmol/L increase; 95% CI, 1.10-2.73; p = 0.01). Causal mediation demonstrated 35.1% of the total effect of plasma on 30-day mortality was mediated by the reduction in lactate among plasma patients. Conclusion Prehospital plasma is associated with reduced 30-day mortality and lactate in severely injured patients. More than one third of the effect of plasma on mortality is mediated by a reduction in lactate. Thus, reducing the severity of hemorrhagic shock appears to be one mechanism of prehospital plasma benefit. Further study should elucidate other mechanisms and if a dose response exists. Level of evidence Therapeutic, level II.

IntroductionSciatic nerve injury is an uncommon but potentially devastating complication in hip and pelvis surgery. Intraoperative nerve monitoring (IONM) was applied since the seventies in neurosurgery and spine surgery. Nowadays, IONM has gained popularity in other surgical specialities including orthopaedic and trauma surgery. Aim of this systematic review is to resume the literature evidences about the effectiveness of intraoperative monitoring of sciatic nerve during pelvic and hip surgery.MethodsTwo reviewers (GC and MD) independently identified studies by a systematic search of PubMed and Google Scholar from inception of database to 10 January 2021. Inclusion criteria were: (a) English written papers, (b) use of any type of intraoperative nerve monitoring during traumatic or elective pelvic and hip surgery, (c) comparison of the outcomes between patients who underwent nerve monitoring and patient who underwent standard procedures, (d) all study types including case reports. The present review was conducted in accordance with the 2009 PRISMA statement.ResultsThe literature search produced 224 papers from PubMed and 594 from Google Scholar, with a total amount of 818 papers. The two reviewer excluded 683 papers by title or duplicates. Of the 135 remaining, 72 were excluded after reading the abstract, and 31 by reading the full text. Thus, 32 papers were finally included in the review.ConclusionsThe use of IONM during hip and pelvis surgery is debated. The review results are insufficient to support the routine use of IONM in hip and pelvis surgery. The different IONM techniques have peculiar advantages and disadvantages and differences in sensitivity and specificity without clear evidence of superiority for any. Results from different studies and different interventions are often in contrast. However, there is general agreement in recognizing a role for IONM to define the critical maneuvers, positions or pathologies that could lead to sciatic nerve intraoperative damage.Level of evidenceLevel 2.

PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events. The clinical benefits presumably result from favorable effects on atherosclerotic plaques. Lipid-core and plaque inflammation have been recognized as main determinants of risk for plaque rupture and cardiovascular events. Both can be noninvasively assessed with carotid MRI. We studied if PCSK9 inhibition with alirocumab induces regression in lipid-core or plaque inflammation within 6 months as measured by MRI. Patients with non-calcified carotid plaque(s) and baseline LDL-C ≥ 70 mg/dl, who were statin-intolerant or taking a low-dose statin (≤ 10 mg per day of atorvastatin or an equivalent), received subcutaneous alirocumab 150 mg every 2 weeks. Carotid MRI was performed at baseline and 6 months after treatment, including pre- and post-contrast images for measuring percent lipid-core volume (%LC) and dynamic contrast-enhanced images for measuring microvessel leakiness (Ktrans), a marker of inflammation. Twenty-eight patients completed the study (69 ± 9 years; 64% male). Alirocumab led to significant changes in LDL-C (p

Lumbosciatica is a frequent reason for consultation in general medicine and emergency medicine with an estimated incidence between 2% and 14%. There are several therapeutic modalities, including infiltrations, which are very controversial. Based on this observation, we conducted a prospective study in which 19 patients had undergone epidural and peri-radicular infiltration; the epidural was the most represented infiltration in 68.4% of the patients, the peri-radicular was in 21.1% of them and the combination of both was in 10.5% of the cases, with only 30.6% of the infiltrations carried out under radioscopy. The molecules used were Triamcinolone Acetonide-based Kenacort and Methylprednisolone Acetate-based Depo-Medrol. The evolution of post-infiltration pain decreased significantly in 94.7% of cases, with a statistically significant difference (p = 0.04). No complications were observed in our patients and none of them had resorted to surgery during the follow-up period except for a single case of recurrence of pain relieved by periodic spaced infiltrations. Despite the small size of our sample, we can conclude that infiltration techniques still have a place in the management of Lumbosciatica alongside the surgery.

Children with a disordered lingual frenulum are said to be more prone to various difficulties in the development process. Although these children tend to present changes in chewing, swallowing and speech, it can be assumed that the voice is practically not focused, with few studies concerned on vocal function (Camargo et al, 2017, 2017a). With the aim of investigating voice quality in children with and without lingual frenulum disorder, 61 children were clinically evaluated regarding the characteristics of the lingual frenulum (Marchesan, 2012) and the perceptual judgments of voice quality in semi-spontaneous (audio) speech samples. Video samples of orofacial clinical examinations and semi-spontaneous (audio) speech samples were recorded in a soundproof room. 28 children presented altered lingual frenulum (19 boys and 09 girls) and 33 frenulum without alterations (20 boys and 13 girls). We adopted the phonetic description of voice quality model as the theoretical background (Laver, 1980) and the Vocal Profile Analysis Scheme – VPAS (Laver et al, 1981; adapted for brazilian portuguese: Camargo, Madureira, 2008) for perceptual data analysis. Voice quality settings regarding the position of lips, tongue (tip and body), jaw, pharyngeal cavity configuration and vocal tract muscle tension occurred in a greater proportion (in terms of number of the occurrences and the degree of manifestation) in children with lingual frenulum disorded. When observing the data differently by male and female subgroups, we estimate that the former accounted for most of the occurrences related to labiodentalization, retracted and lowered tongue body and pharyngeal constriction. In the girls' subgroup, pharyngeal constriction was also recurrent. With regard to our previous explorations on the topic (Camargo et al, 2017, 2017a), we were able to advance in terms of a broader understanding of children's voice quality profiles and, particularly, those related to congenital orofacial motricity limitations. The relationships between size and position of the hyoid bone in children with an altered frenulum of the tongue (Ardekani et al, 2016), especially the raised and posterior position of the hyoid bone and the posteriorization of the jaw compared to children without frenulum disorerss, seem to influence the voice quality findings reported in this study. The high incidence rates of dysphonia in childhood tend to make it difficult to associate the alterations of the lingual frenulum to phonatory settings, although they may, hypothetically, appear as aggravating factors for dysphonia.

Background Central precocious puberty (CPP) has been associated with loss-of-function mutations in 2 paternally expressed genes (MKRN3 and DLK1). Rare defects in the DLk1 were also associated with poor metabolic phenotype at adulthood. Objective Our aim was to investigate genetic and biochemical aspects of DLK1 in a Spanish cohort of children with CPP without MKRN3 mutations. Patients A large cohort of children with idiopathic CPP (Spanish PUBERE Registry) was studied. Genomic deoxyribonucleic acid was obtained from 444 individuals (168 index cases) with CPP and their close relatives. Automatic sequencing of MKRN3 and DLK1 genes were performed. Results Five rare heterozygous mutations of MKRN3 were initially excluded in girls with familial CPP. A rare allelic deletion (c.401_404 + 8del) in the splice site junction of DLK1 was identified in a Spanish girl with sporadic CPP. Pubertal signs started at 5.7 years. Her metabolic profile was normal. Familial segregation analysis showed that the DLK1 deletion was de novo in the affected child. Serum DLK1 levels were undetectable (A and g.-223 G>A) in 2 girls with CPP. However, both had normal DLK1 serum levels. Conclusion Loss-of-function mutations of DLK1 represent a rare cause of CPP, reinforcing a significant role of this factor in human pubertal timing.

To report our experience in non-contact wide-angled visualization with chandelier-assisted scleral buckling (SB) in uncomplicated primary rhegmatogenous retinal detachments (RRD). Retrospective case series of 282 eyes that underwent non-contact wide-angled visualization with chandelier-assisted SB and were followed for a mean of 13.5 months. There were 160 male patients. The average age was 42.6 years old. There were 262 eyes that were phakic, 18 pseudophakic, and 2 aphakic. Two-thirds of eyes presented with the macula detached. Eyes had an average of 1.6 breaks. The single operation anatomic success rate was 85.1% (240/282). The pre-op visual acuity improved from 1.21 to 0.76 logMAR at 6 months (p < 0.0001). Complications included a case of scleral laceration, choroidal hemorrhage, 3 epiretinal membranes, 1 macular fold, and 4 eyes with buckle exposure. Non-contact wide-angled visualization with chandelier-assisted SB compares favorably with conventional SB for primary uncomplicated primary RRD.

Background Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®. Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. Results LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p Conclusions LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value.

Tumors of the peripheral nerves are not well described. Plexiform neurofibromas are common NF1 benign tumors that carry a low malignant risk of transformation. In some area where the conventional therapies (clinical trial) are not available, surgery remains the gold standard although this one is not radical. There is not a lot of publications related to this subject in Africa. The aim of study is to share our experience and show the difficulties of managing this pathology in children. We report a case of a 4 year old boy without any family history of neurofibromatosis. He presented to our department of neurosurgery at renaissance hospital of Ndjamena (Chad) with primary skin concern about a right lumbar swelling which was progressive increase in size over the last few years. Physical examination revealed the presence of several cafe-au-lait macules (CALM) more than forty, freckling, hypertrichosis, hyperpigmentation, and thoraco-lumbar scoliosis without other associated lesions. Ultrasonography, CT scan and Magnetic resonance imaging (MRI) of the swelling was done, and gave features description of this lesion. The patient underwent surgery and the diagnosis of plexiform neurofibromatosis was made at the histological examination. After a follow-up of 16 months there is no tumor recurrence. A regular follow-up is necessary for this young patient. The surgery has an aesthetic purpose and it delays the progression of the disease.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

BACKGROUND: Anti-PD-1 checkpoint inhibitor (CPI) monotherapy has demonstrated modest activity in pre-treated mTNBC, with single digit objective response rates (ORR) observed. Our prior data suggests that local electroporation after intratumoral administration of tavokinogene telseplasmid (IT-tavo-EP), a plasmid encoding the proinflammatory cytokine IL-12, can render CPI non-responsive pre-treated mTNBC sensitive to CPI therapy. The phase II KEYNOTE-890/OMS-I141 study was therefore designed to evaluate IT-tavo-EP and IV pembrolizumab in patients with mTNBC previously treated with chemotherapy +/- CPI therapy. METHODS: Patients with histologically confirmed inoperable locally advanced or metastatic TNBC with at least 1 line of prior systemic therapy for advanced disease, including prior CPI therapy, were eligible. Patients were required to have RECIST v1.1 measurable disease with at least 1 anatomically distinct cutaneous or subcutaneous lesion accessible for intratumoral injection and electroporation. Scans were obtained every 12 weeks. Patients received pembrolizumab 200 mg IV on day 1 of each 3-week cycle and IT-tavo-EP at a concentration of 0.5 mg/mL and dose volume of ~1/4 of the calculated lesion volume to the accessible lesion(s) on days 1, 5, and 8 every 6 weeks. The primary endpoint of this open-label, non-randomized phase II trial is ORR by investigator review. Secondary endpoints include safety and tolerability of the combined therapy, duration of response, progression-free survival (PFS), immune PFS and overall survival. The correlation between changes in the immune cell subsets and response to treatment was also evaluated. RESULTS: At the time of abstract submission, 16 of the planned 25 patients have been enrolled and 11 patients completed a post-treatment RECIST v1.1 assessment at the initial 12-week evaluation or discontinued prior to assessment. Patients had a median of 3 prior lines of therapy for advanced disease. Partial responses have been observed in 3 patients (ORR 27.3%), including a deep confirmed response in a patient with multiple liver, bone, skin and nodal metastases and a short disease-free interval following neoadjuvant chemotherapy. Regression of IT-tavo-EP untreated lesions have been observed. Treatment was well tolerated and any grade treatment emergent adverse events (AEs) regardless of attribution were observed in 11 of 16 (68.8%) [grade ≥3 in 6 of 16 (37.5%)]. Only one grade ≥3 AE was attributed to pembrolizumab and none were attributed to IT-tavo or EP. Patients demonstrated immunological responses in blood consistent with an IL-12-associated mechanism of action, including on-treatment reduction of peripheral gMDSC suppressors. Additional biomarker analysis of patient tumor and blood samples are ongoing. CONCLUSIONS: When compared to the results of KEYNOTE-086, which demonstrated a 5.3% ORR in pretreated mTNBC patients with pembrolizumab monotherapy, our preliminary data from patients who have reached an assessment time-point suggests that IT-tavo-EP may enhance sensitivity to pembrolizumab in this patient population. Updated data will be presented. Citation Format: Melinda L. Telli, Irene Wapnir, Bianca Devitt, Katharine Cuff, Hatem Soliman, Shaveta Vinayak, David A. Canton, Christopher Twitty, Kellie Malloy Foerter, Rohit Joshi. Phase 2, open-label study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation in combination with intravenous pembrolizumab therapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC) (KEYNOTE- 890/OMS-I141) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-04.

Background It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. Methods In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)]. Results In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P Conclusion Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

A Artrite Idiopatica Juvenil (AIJ) e uma artrite de etiologia desconhecida que persiste por pelo menos seis semanas e inicia em pacientes de ate dezesseis anos. A AIJ do tipo sistemica (AIJS) representa dez por cento das artrites que se iniciam na infância. A febre de origem indeterminada e uma de suas principais manifestacoes e o quadro comumente confunde-se a um quadro infeccioso, o que acaba impedindo o inicio precoce de uma terapia anti-inflamatoria. O presente trabalho e um estudo descritivo do tipo Relato de Caso, utilizando-se de informacoes obtidas atraves da analise do prontuario medico da paciente e o decorrer da historia clinica que contribuiram para o diagnostico desta doenca.

Frontal sinus aspergillosis is a rare infection that can be usually associated with immunocompromised states and life-threatening with high mortality rate. The authors report in a developing country a case of immunocompetent patient with left unilateral frontal headache, associated with left eye ptosis. The Brain CT Scan revealed frontal sinus aspergillosis. She underwent surgery followed by itraconazole cure. The outcome is successful after a period of 14 months with resolution of symptomatology. Anatomopathological examination confirmed aspergillosis. They share their experience of management of this disease in a country where neurosurgery is very young specialty and where molecules against aspergillosis are not available.

Purpose To propose a method for quantification of vitreous hemorrhages (VH) termed minimum image gain (MIG). Therefore, to obtain MIG measurements in patients with VH and to compare them to normal controls; to compare results between graders; and to obtain and compare MIG from two different ultrasound systems. Methods Retrospective and cross-sectional, observational, and comparative study performed in two parts: Part 1) Retrospective comparison of MIG in VH vs controls by two experienced graders, with intra/inter-observer variability: MIG technique is described. MIG is performed retrospectively in two groups, VH patients and normal controls. Groups are compared with independent samples t-test. Intra- and interobserver variability between graders was obtained. Part 2) Cross-sectional analysis of variability from nonexperienced graders and with different ultrasound systems: MIG is performed in cross-sectional measurements of VH patients, by two unexperienced graders, and with two ultrasound systems. Interobserver variability and Bland-Altman plot with levels of agreement (LoA) were obtained. Results Part 1: 50 patients with VH resulted in mean MIG: 52.8 dB; 34 controls resulted in mean MIG: 77.97 dB. Independent samples t-test resulted in a statistical significant difference. Intra- and inter-observer variability resulted in an almost perfect agreement between experienced graders. Part 2: 63 patients with VH, mean MIG: 56.19 dB. Inter-observer variability resulted in a very high agreement between unexperienced observers. LoA resulted in a statistical difference between the two ultrasound systems. Conclusion MIG may provide an objective and reproducible way to quantify vitreous hemorrhage density and potentially any vitreous humor opacity. Agreement is high even with unexperienced graders. However, the two ultrasound systems analyzed may not be interchangeable.

Introduction: Loss-of-function mutation of MKRN3 represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with MKRN3 defects are unknown. Objective: To describe the clinical and hormonal features of patients with CPP with or without MKRN3 mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated. Patients and Methods: Twenty-nine female patients with CPP due to loss-of-function mutations in the MKRN3 and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to MKRN3 defects reached final height (FH). Results: At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without MKRN3 mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without MKRN3 mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to MKRN3 mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to MKRN3 mutations and 5.9% in those with idiopathic CPP. Conclusion: Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without MKRN3 mutations, suggesting the absence of deleterious effects of MKRN3 defects in young female adults’ life.

Atherosclerotic cardiovascular disease remains a worldwide epidemic and one of the leading causes of death nowadays. Vessel wall imaging can be used to understand the development and progression of atherosclerosis, but it is rarely done because of the high cost. We recently identified the Osteoarthritis Initiative, a large prospective cohort study of knee osteoarthritis, which might serve as a valuable source for atherosclerosis research with its serial knee magnetic resonance imaging data. We have found that these images are suitable for vessel wall image analysis of the lower extremity arteries. Here, we will introduce the Osteoarthritis Initiative data set and explain why it could be used for cardiovascular research purposes. Also, we will briefly comment on peripheral artery atherosclerosis as it is covered in the Osteoarthritis Initiative image data set and review the use of vessel wall imaging for studying atherosclerosis. We think data mining of imaging studies, not originally designed on cardiovascular research, can not only maximize the value of the imaging data set but also boost our understanding of atherosclerosis.

Objective— Diabetes mellitus is associated with high-risk atherosclerotic plaques. This study aimed to compare characteristics of carotid atherosclerotic plaques in symptomatic Chinese diabetic and nondiabetic patients using vessel wall magnetic resonance imaging. Approach and Results— Patients with cerebral ischemic symptoms in the anterior circulation and carotid atherosclerotic plaque determined by ultrasound were recruited from a cross-sectional, observational, multicenter study of CARE-II (Chinese Atherosclerosis Risk Evaluation). All patients underwent magnetic resonance imaging for carotid arteries. The morphological and compositional characteristics of carotid plaques were compared between diabetic and nondiabetic patients using linear (continuous variables) and logistic regression (binary variables). In a total of 584 recruited patients, 182 (31.2%) had diabetes mellitus. From the univariate analysis, diabetic patients had significantly greater mean wall area (33.7 versus 31.1 mm 2 ; P =0.002), maximum wall thickness (3.2 versus 2.8 mm; P P P =0.001), lipid-rich necrotic core (77.5% versus 58.5%; P P =0.011) than nondiabetic patients. After adjusting for clinical characteristics, the differences in presence of calcification ( P =0.018) and lipid-rich necrotic core ( P =0.001) remained statistically significant. Conclusions— Symptomatic Chinese diabetic patients are more likely to have carotid plaques with calcification and lipid-rich necrotic core than nondiabetic patients, suggesting that diabetic patients may develop more severe atherosclerotic disease that should be accounted for in their clinical management.

Aims To evaluate the temporal trend of newly diagnosed Type 1 Diabetes cases over a 35-year period in a reference Pediatric Endocrinology service in the city of Belo Horizonte, Brazil. Methods Subjects were all children and adolescents diagnosed with Type 1 Diabetes in the Federal University of Minas Gerais Hospital. Information collected included: gender, age and date of Type 1 diabetes diagnosis. Temporal trends were analyzed between 1980 and 2014 and divided in 5-year intervals. Results During this period 642 children and adolescents were diagnosed with Type 1 diabetes. From 1980 to 1994 there was an increase in the proportion of children diagnosed between 0 and 4 years old, followed by progressive decrease in the subsequent decades (47% in 1990–1994 to 20% in 2010–2014; p = 0.01). There was an increase in the proportion of children diagnosed between 10 and 18 years old (13% in 1990–1994 to 54% in 2010–2014; p = 0.01). There was no statistical difference in the proportion of children diagnosed between 5 and 9 years old through the studied time. Conclusions In the studied population Type 1 Diabetes in infants and toddlers seems to be decreasing throughout the years while in the age group older than 10 years, it seems to be increasing.

Objetive: The aim of the present study was evaluate the effect of the 6-minute walk test (6MWT) on the secretory immunoglobulin A (sIgA) kinetics in whole saliva of healthy elderly women. Methods: Nine healthy, elderly females (age 61 ± 6.7 years) performed the 6 MWT. Saliva samples and heart rate (HR) were measured in basal, immediately (IPE), and 30 minutes after the 6 MWT (30-Post Ex). Blood lactate [La] was measured at the same intervals. The ELISA assay was used to determine the sIgA concentrations [sIgA]. The Biuret assay was employed to determine the total proteins levels in saliva. Results: The exercise intensity reached by the participants was ≈ 84 + 16% of maximum HR. Baseline [La] was 1.8 ± 0.9 mmol/L. [La] at IPE increased 3.4 mmol/L above baseline (p = 0.02). [sIgA] increased by 233.3 + 109.3 % at IPE and remained 211.2 + 100.1 % greater at 30-Post Ex compared with basal (p = 0.02). The 6 MWT did not modify total proteins levels (p > 0.05). Conclusion: The 6 MWT, performed to submaximal intensity, appears to be enough of a stimulus to increases sIgA levels in healthy elderly women independent of total proteins concentration in saliva.

The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals.Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. Simulations for each time window and for different types of vaccines and production rates were run to find the optimal time window between doses, that is, the one that minimizes the number of deaths.We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to apply the second dose as soon as possible, while for high first-dose efficacy, the optimal window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the optimal window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.

Background An artificial intelligence vessel segmentation tool, Fully Automated and Robust Analysis Technique for Popliteal Artery Evaluation (FRAPPE), was used to analyze a large databank of popliteal arteries imaged through the OAI (Osteoarthritis Initiative) to study the impact of atherosclerosis risk factors on vessel dimensions and characterize remodeling patterns. Methods and Results Magnetic resonance images from 4668 subjects contributing 9189 popliteal arteries were analyzed using FRAPPE. Age ranged from 45 to 79 years (median, 61), and 58% were women. Mean lumen diameter, mean outer wall diameter, and mean wall thickness (MWT) were measured per artery. Their median values were 5.8 mm (interquartile range, 5.2–6.5 mm), 7.3 mm (interquartile range, 6.7–8.1 mm), and 0.78 mm (interquartile range, 0.73–0.84 mm) respectively. MWT was associated with multiple cardiovascular risk factors, with age (4.2% increase in MWT per 10‐year increase in age; 95% CI, 3.9%–4.5%) and sex (8.6% higher MWT in men than women; 95% CI, 7.7%–9.3%) being predominant. On average, lumen and outer wall diameters increased with increasing MWT until the thickness was 0.92 mm for men and 0.84 mm for women. After this point, lumen diameter decreased steadily, more rapidly in men than women (−7.9% versus −6.1% per 25% increase in MWT; P Conclusions FRAPPE has enabled the analysis of the large OAI knee magnetic resonance imaging data set, successfully showing that popliteal atherosclerosis is predominantly associated with age and sex. The average vessel remodeling pattern consisted of an early phase of compensatory enlargement, followed by a negative remodeling, which is more pronounced in men.

BackgroundRoutine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time.MethodsWe fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection, we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection.FindingsWe estimated that the probability that the PCR test detected infection peaked at 77% (54 - 88%) 4 days after infection, decreasing to 50% (38 - 65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1–3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33-76%) of symptomatic cases prior to onset and 94% (75-99%) of asymptomatic cases within 7 days if test results were returned within a day.InterpretationOur results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast.FundingWellcome Trust, National Institute for Health Research (NIHR) Health Protection Research Unit, Medical Research Council (UKRI)

The SARS-CoV-2 variant of concern (VOC) P.1 (Gamma variant) emerged in the Amazonas State, Brazil, in November 2020. The epidemiological consequences of its mutations have not been widely studied, despite detection of P.1 in 36 countries, with local transmission in at least 5 countries. A range of mutations are seen in P.1, ten of them in the spike protein. It shares mutations with VOCs previously detected in the United Kingdom (B.1.1.7, Alpha variant) and South Africa (B.1.351, Beta variant). We estimated the transmissibility and reinfection of P.1 using a model-based approach, fitting data from the national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December-2020 to February-2021. Here we estimate that the new variant is about 2.6 times more transmissible (95% Confidence Interval: 2.4–2.8) than previous circulating variant(s). Manaus already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus and our fitted model attributed 28% of Manaus cases in the period to reinfections by P.1, confirming the importance of reinfection by this variant. This value is in line with estimates from blood donors samples in Manaus city. Our estimates rank P.1 as one of the most transmissible among the SARS-CoV-2 VOCs currently identified, and potentially as transmissible as the posteriorly detected VOC B.1.617.2 (Delta variant), posing a serious threat and requiring measures to control its global spread. SARS-CoV-2, the virus that causes COVID-19, can mutate into variants which might have different characteristics such as increased ability to spread. The P.1 variant, also known as Gamma, was first identified in Manaus, Brazil. Here, we use mathematical and statistical methods to model the spread of P.1 in Manaus and to determine the potential for people getting re-infected with P.1, comparing it to previous circulating variants in the region. We estimate that P.1 spreads 2.6 times more easily than these other variants and that nearly a third of cases over the period studied were reinfections with P.1. These findings help us to understand whether P.1 is likely to be more difficult to control than other variants and what sort of measures might be needed. Coutinho et al. use genomic and epidemiological data from Manaus, Brazil, to estimate the transmissibility and potential for reinfection with the SARS-CoV-2 variant-of-concern P.1 (gamma). Using mathematical modelling, the authors estimate that P.1 is 2.6 times more transmissible than previous SARS-CoV-2 variants circulating in Manaus and underlies a large proportion of reinfections in Manaus.

Lay abstract This study investigated the use of quantum dots (QDs) to treat very advanced retinitis pigmentosa (RP), a disease characterized by progressive loss of peripheral and then central vision. QDs are sometimes called ‘artificial atoms’. If they are injected into the eye, they settle in the retina, the light-sensing layer of cells that is damaged by RP. When light enters the eye, it is absorbed by the QDs in the retina, and the light energy is converted to electrical energy. Electrical stimulation has been shown to benefit degenerating retina, as occurs in RP, and hence QDs may have the potential to improve or preserve vision in people with RP. This preliminary study recruited 20 people with very severe RP and injected QDs into their eyes. We aimed to see whether the QDs were safe. No adverse reactions were attributed to the QDs, and the average vision of treated eyes improved, whereas the participants’ untreated fellow eyes showed no real change in vision. Although encouraging, these results are only preliminary, and a larger study is planned to explore these findings.

Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

BACKGROUND: Cut-out is the most common mechanical complication of the osteosynthesis of pertrochanteric fractures. This complication determines a significant increase in morbidity in elderly patient. Cut-out is defined as the varus collapse of the femoral head-neck fragment with the extrusion of the cephalic screw. Surgical treatment of cut-out might lead to further complications, longer rehabilitation, increased social burden and healthcare system costs. The aim of the study is to identify the predictors of cut-out to prevent its occurrence. MATERIALS AND METHODS: Study population included all patients affected by extracapsular fracture of the proximal femur who were admitted and treated with short cephalomedullary nailing at the Cattinara Hospital-ASUITS of Trieste between 2009 and 2014. A retrospective analysis of clinical and radiographic data was carried out and cut-out cases recorded. The data collected on the study population were analyzed to find an eventual correlation with the occurrence of cut-out. The independent variables were age, gender, side of the fracture, ASA class, Evans classification, nailing system, quality of reduction, TAD, CalTAD, and Parker ratio. RESULTS: The study population counted 813 cases, with an F:M ratio of 4:1 and a mean age of 84.7 years. The cut-out was recorded in 18 cases (2.2%). There was no statistically significant association between cut-out and age, sex, side of fracture, ASA class, and nailing system. The Evans classification, the quality of reduction, the TAD, the CalTAD, and the Parker's ratio demonstrated a significant correlation at univariate analysis with cut-out. The results of multivariate analysis confirmed that TAD, Parker AP, and quality of reduction were independently significantly correlated to cut-out. CONCLUSION: The results of the present study demonstrate that good quality of reduction and correct position of the lag screw are likely to decrease the risk of cut-out complication. A nomogram for cut-out prediction is proposed for clinical validation.

Background Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available. Methods Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks. Results The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks. Conclusion The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.

Proximal humerus fractures (PHF) are common injuries in the elderly population. Conservative treatment is indicated for undisplaced and stable fractures, which account for almost 80% of the cases. More complex fracture patterns might need surgery, with a wide variety of indication criteria and surgical techniques described in the literature. Surgical treatment should be reserved for patients in good clinical conditions, autonomous in daily living activities and able to adhere to postoperative rehabilitation protocols. In the elderly population with severe osteoporosis, cognitive impairment and clinical comorbidities, the risk of surgical failures is high. In these patients, the choice between surgical and conservative treatment, as well as for the type of procedure, is even more difficult, with no general consensus in the literature. Final indication is usually conditioned by surgeon’s experience and preference. Two independent reviewers (B.H and G.G) independently extracted studies on proximal humeral fractures. All selected studies were screened independently (B.H and G.G) based on title and abstract. Then the full text of any article that either judged potentially eligible was acquired and reviewed again. Any disagreement was resolved by discussing the full text manuscripts. Aim of the present paper is to review the literature about indications and results of osteosynthesis for proximal humerus fragility fractures in the elderly population.

Historically, rheumatoid arthritis represents the typical indication for elbow arthroplasty. Indications have been extended to include primary osteoarthritis, post-traumatic arthritis, and acute distal humerus fractures. Before the introduction of elbow arthroplasty, there were many surgical procedures, such as the interposition arthroplasty described for the first time by Schüller in 1893. Elbow arthroplasty was mainly developed as a response to the high failure rate of these procedures. The first prosthetic replacement was described by Robineau in 1925. Over the years, the prosthesis has continued to evolve in the attempt to optimize this treatment in order to avoid complications, like loosening and instability, and to achieve better postoperative outcomes. In response to these failures, three design concepts have been developed: linked or semi-constrained, unlinked, and convertible prosthesis. Radial head arthroplasty, described for the first time in the 1940s, had remarkable improvements and is nowadays recommended for comminuted radial head fractures. Despite the evolution of elbow arthroplasty designs, concerns regarding loosening in the long term, and in younger patients with high demands, are still present

Background: Soft tissues (wound dehiscence, skin necrosis) and septic (wound infection, osteomyelitis) complications have been historically recognized as the most frequent complications in surgical treatment of high-energy proximal tibia fractures (PTFs). Staged management with a temporary external fixator is a commonly accepted strategy to prevent these complications. Nonetheless, there is a lack of evidence about when and how definitive external or internal definitive fixation should be chosen, and which variables are more relevant in determining soft tissues and septic complications risk. The aim of the present study is to retrospectively evaluate at midterm follow-up the results of a staged management protocol applied in a single trauma center for selective PTFs. Methods: The study population included 24 cases of high-energy PTFs treated with spanning external fixation followed by delayed internal fixation. Severity of soft tissues damage and fracture type, timing of definitive treatment, clinical (ROM, knee stability, WOMAC and IOWA scores) and radiographic results as well as complications were recorded. Results and conclusion: Complex fracture patterns were prevalent (AO C3 58.3%, Schatzker V–VI 79.1%), with severe soft tissues damage in 50% of cases. Mean time to definitive internal fixation was 6 days, with double-plate fixation mostly chosen. Clinical results were highly satisfying, with mean WOMAC and IOWA scores as 21.3 and 82.5, respectively. Soft tissue complication incidence was very low, with a single case of wound superficial infection (4.3%) and no cases (0%) of deep infection, skin necrosis or osteomyelitis. Staged management of high-energy PTFs leads to satisfying clinical and radiographic results with few complications in selected patients.

Atopic dermatitis (AD) therapeutic approach calls for a long-term treatment. Treatment options for AD have recently undergone a revolutionary change by the introduction of the first biologic drug. Availability in daily practice of the last version of international AD guidelines, taking peculiarities of the country into account, can contribute to good clinical practice in Italy. To adapt European Dermatology Forum (EDF) guidelines for AD to the Italian medical–legal context, the EDF guidelines were assessed independently by two independent Italian renowned experts in the field and further integrated with articles published and systematically reviewed before May 2019. The first draft was collegially corrected and updated by the members of the SIDEMAST, ADOI, and SIDAPA. Recommendation levels (A; B; C; D) were graded based on the evidence levels (1–4). The adapted guidelines presented here focus on topical and systemic therapies in AD patients, both children and adults. As opposed to previous Italian guidelines, they include indications about biologics. New relevant evidence available from very recent literature and peculiarities of the Italian medical and legal context have been integrated in the revision process. If compared to general guidelines for AD not adapted to a specific national and cultural context, a revision for specific Italian needs is now available: It comprises the option of implementing the new biologic treatments and is likely to provide an important contribution to the improvement of clinical practice in Italy. Cooperation between patients, dermatologists, allergologists, and pediatricians remains mandatory in AD management. The authors of the present revision recommend an update of the Italian guidelines to be performed at least every second year.

Background It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events. Methods In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR 2) with progression of carotid plaques and the SPRINT cardiovascular endpoint. Results One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events. Conclusions Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening. Trial Registration NCT01475747, registered on November 21, 2011.

Contains fulltext : 232930.pdf (Publisher’s version ) (Closed access) BACKGROUND: On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. METHODS: In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to

Highlights • We found a high asymptomatic rate in vulnerable people with epilepsy. • Enhanced surveillance allows to quickly contain outbreaks. • We report a low rate of COVID-19 morbidity and mortality in a long-term care facility. • Preventative measures allow reducing resident-to-resident and -to-caregiver transmission. • Children and young adults appear to have lower infection rates., In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March–6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth’s (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated procedure for high-throughput SARSCoV-2 detection by RT-LAMP in 25 minutes that is robust, reliable, repeatable, sensitive, specific, and inexpensive © 2021. Buck MD et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Made available in DSpace on 2021-07-14T10:27:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-07. Added 1 bitstream(s) on 2021-07-14T11:30:56Z : No. of bitstreams: 1 S1415-790X2021000100204.pdf: 254165 bytes, checksum: 1ce58ee89594d5c66bb2504c987acc90 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) This article discusses the epidemic situation of Covid-19 in Brazil, in the face of the emergence of a new strain called P.1, which is more transmissible and may be associated with reinfection. Given the collapse of hospital care in Manaus in January 2021 and the results of three recent preprints, each that reports increased transmissibility of the P.1 variant, we propose some urgent measures. Genomic surveillance based on multi-step diagnostics, starting with RT-PCR type tests and up to sequencing, should be established. Efforts to identify reinfections associated with this variant and the update of its definition in protocols should be prioritized, and studies on the efficacy of currently available vaccines in Brazil concerning the new variant should be conducted. We also propose improving the Brazilian health surveillance system such that genomic surveillance is coordinated and thereby better able to respond to future emergencies in a more timely fashion. We call on the public agents involved in health surveillance to share data and information regarding the epidemic in a clear, fast and transparent way. Finally, we propose a greater engagement in inter-institutional cooperation of all those involved in the response and production of knowledge about the pandemic in our country. Universidade Estadual de Campinas Universidade Federal do ABC Universidade Estadual Paulista “Júlio de Mesquita Filho” Observatório COVID-19 Universidade de São Paulo Universidade de São Paulo, School of Medicine Universidade de São Paulo, Department of Political Science Johns Hopkins University Universidade Federal de Santa Catarina Universidade Estadual de Campinas, School of Medical Sciences Universidade Federal do Maranhão Santa Casa de São Paulo School of Medical Sciences Universidade Estadual Paulista “Júlio de Mesquita Filho” CNPq: 315854/2020-0; 141698/2018-7; 313055/2020-3; 312559/2020-8; 311832/2017-2; 305703/2019-6; 301631/2018-2 FAPESP: 2019/26310-2; 2017/26770-8; 2018/26512-1; 2018/24037-4; 2016/01343-7

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19–65 years, weight: 56–137 kg, BMI: 23–44) and 69 women (age: 18–55 years, weight: 41–126 kg, BMI: 22–39) was analyzed in duplicate by western blot. VO2max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2max per kg of legs lean mass (VO2max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (β = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2max-LLM had also predictive value (β = 0.09). There was a significant fat % by VO2max-LLM interaction, such that for subjects with low fat %, VO2max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.