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OBJECTIVE: This study aimed to develop a new histological scoring system for use in a partial-thickness cartilage repair animal model. Although previous papers have investigated the regeneration of articular cartilage, the good results achieved in small animals have not been replicated in large animal models or humans, possibly because of the frequent use of models with perforation of the subchondral bone plates. Partial-thickness lesions spare the subchondral bone, and this pattern is the most frequent in humans; therefore, new therapies should be tested using this model. However, no specific histological score exists to evaluate partial-thickness model results. METHODS: Histological sections from 30 ovine knees were reviewed to develop a new scoring system. The sections were subjected to H&E, Safranin O, and Masson’s trichrome staining. RESULTS: This paper describes a new scoring tool that is divided into sections in detail: repair of tissue inside the lesion, cartilage around the lesion and degenerative changes at the base of the lesion. Scores range from 0 to 21; a higher score indicates better cartilage repair. DISCUSSION: Unlike existing tools, this new scale does not assign points for the positioning of a tidemark; we propose evaluation of the degenerative changes to the subchondral bone and calcified cartilage layer. It is necessary to remove the whole joint to access and study the evolution of the lesion as well as the surrounding tissue. CONCLUSION: This article emphasizes the importance of a partial-thickness animal model of cartilage repair and presents a new histological scoring system.

Since the outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 has had a wide range of effects on human health. This paper summarizes the data related to the effects of the SARS-CoV-2 infection on human reproduction. Both the male and female reproductive tract express high levels of receptors and proteins needed for viral cell entry. There is presently no evidence that gametes are affected by the infection. Male fertility may be temporarily reduced due to inflammatory responses following infection. The endometrium is highly susceptible to SARS-CoV-2 cell entry; however, it remains unclear whether this could alter receptivity and embryo implantation. Menstrual cycle changes were reported in women who experienced severe infection; however, they tended to be reversible. For couples undergoing assisted reproduction treatment, the pandemic led to a significant psychological burden, with changes in lifestyle that could directly affect the success of the treatment. Human reproduction societies recommend screening all patients prior to cycle initiation and avoiding treatment of women with severe comorbidities until the pandemic is under control. Finally, for pregnant women, it is expected that the infection is more severe in women in the third trimester and in those with comorbidities. Those who are symptomatic for SARS-CoV-2 are more likely to have increased rates of prematurity and intrapartum fetal distress than those who are asymptomatic. Vertical transmission cannot be completely ruled out, but neonatal infection rates are low. Vaccination appears to be safe and is indicated for use in pregnant and lactating women because the benefits outweigh the risks.

This study aimed to assess the correlation between Sjögren's Syndrome (SS) and adverse pregnancy outcomes, with the aim of providing a basis for preconception and pregnancy interventions in women with SS.A search of electronic databases in English and Chinese databases from January 2005 to December 2021, was conducted to collect the literature of case-control studies or cohort studies on the association between SS and pregnancy outcome studies. Literature inclusion and data extraction were performed according to established criteria, and the Newcastle-Ottawa scale was used to evaluate the quality of the literature. Stata 15 software was used for meta-analysis.A total of nine papers were included in this study. Meta-analysis results showed that SS was associated with spontaneous abortion (RR = 8.85, 95% CI 3.10‒25.26), preterm birth (RR = 2.27, 95% CI 1.46‒3.52), low birth mass (RR = 1.99, 95% CI 1.34‒2.97), and birth defects (RR = 4.28, 95% CI 3.08‒5.96).SS can increase the incidence of adverse pregnancy outcomes.

OBJECTIVES: Dengue cases range from asymptomatic to severe, eventually leading to hospitalization and death. Timely and appropriate management is critical to reduce morbidity. Since 1980, dengue has spread throughout Brazil, affecting an increasing number of individuals. This paper describes age and regional differences in dengue’s clinical presentation and associated risk of hospitalization based on more than 5 million cases reported to the Brazilian Ministry of Health from 2000-2014. METHODS: We performed a retrospective analysis of ∼5,450,000 dengue cases, relating clinical manifestations and the risk of hospitalization to age, gender, previous infection by dengue, dengue virus serotype, years of formal education, delay to first attendance and the occurrence of dengue during outbreaks and in different Brazilian regions. RESULTS: Complicated forms of dengue occurred more frequently among those younger than 10 years (3.12% vs 1.92%) and those with dengue virus 2 infection (7.65% vs 2.42%), with a delay to first attendance >;2 days (3.18% vs 0.82%) and with ≤4 years of formal education (2.02% vs 1.46%). The risk of hospitalization was higher among those aged 6-10 years old (OR 4.57; 95% CI 1.43-29.96) and those who were infected by dengue virus 2 (OR 6.36; 95% CI 2.52-16.06), who lived in the Northeast region (OR 1.38; 95% CI 1.11-2.10) and who delayed first attendance by >;5 days (composite OR 3.15; 95% CI 1.33-8.9). CONCLUSIONS: In Brazil, the occurrence of severe dengue and related hospitalization is associated with being younger than 10 years old, being infected by dengue virus 2 or 3, living in the Northeast region (the poorest and the second most populated) and delaying first attendance for more than 2 days.

We read the paper by Oliveira C et al. () describing the hemodynamic effects of different maternal positions on maternal and fetal cardiovascular and respiratory indices with interest. The authors observed no differences in the measured parameters (maternal heart rate, blood pressure, oxygen saturation, respiratory rate or fetal heart rate) between the left lateral position, Fowler’s position and supine position, but they did observe reductions in the maternal respiratory rate and systolic blood pressure in Fowler’s position compared with lying [...]

The advent of liver transplantation provided a treatment option for several pediatric terminal liver diseases. In September 1989, we performed the first pediatric liver transplantation in a child with biliary atresia at the Instituto da Crianca do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo after an extensive program of basic science and animal training. Thanks to institutional efforts and the dedication of a multi-disciplinary team composed of doctors, nurses, hospital administrators, pharmacists, physiotherapists, nutritionists, social workers and psychologists, it was possible for us to create and maintain a Brazilian pediatric liver transplantation program that is comparable to those of the world's best centers. From 1989 to the present, we have performed 680 liver transplantations in children with different terminal liver diseases, including the most severe cases of fulminant hepatic failure. However, the scarcity of suitable deceased donors has been a great problem for all liver transplantation programs, particularly in the pediatric area because the need to reduce the volume of liver grafts and the relative severity of the clinical conditions of our patients make the procurement of deceased donors even more difficult and selective. The positions of liver recipient candidates on the waiting list (a single list for adults and children) were based on chronologic criteria until June of 2006 and the mean time from inclusion on the list until transplantation was three years. Consequently, waiting-list mortality (affecting more than 50% of patients) was an important problem that had yet to be solved. From that time until the present, despite the introduction of the Pediatric End-stage Liver Disease (PELD)/Model for End-stage Liver Disease (MELD) criteria for the inclusion and classification of patients based on the severity of their hepatic disease and clinical conditions, the waiting-list mortality rate has remained persistently high. In this context, we began a program of living donor transplantation and the first procedure was performed in 1998. To date, careful selection and preparation of potential living donors have allowed us to perform 280 procedures, with a low morbidity rate and no donor complications or deaths 1. Resection of the left lateral segment or the left lobe (which provides sufficient liver mass for pediatric recipients) is a procedure that is relatively safe for the donors 2. Our center's surgical team includes only pediatric surgeons, with extensive experience in pediatric liver surgery and liver transplantation, including experience with adolescents, which allows us to perform the donor hepatectomies without the participation of adult surgeons. We emphasize that the donor and recipient procedures are performed in adjoining rooms, with full synchronization, in an exclusively pediatric hospital that has undergone logistical and structural adjustments to allow for the procedures in the adults to be performed safely and comfortably. Additionally, in the early postoperative period, the donor (in general, a mother or father) and the recipient can stay together in the same hospital. Finally, another advantage is that the team of pediatric surgeons can perform adequate early and late follow-ups of all donors. Regarding the benefits of living donor transplantation for the recipients, the advantages of good-quality grafts outweigh the technical difficulties related to the smaller caliber of the vascular anastomoses and to biliary reconstruction 3. Thus, despite the introduction of MELD and PELD scores to determine waiting-list positions, living donor liver transplantation maintains a crucial role in our program because children can be treated earlier and receive extensively evaluated grafts with optimal function that have been exposed to minimal cold ischemia. However, liver transplantation is a complex procedure, and as such, it is still associated with several postoperative complications. Surgical complications may involve the vascular (hepatic artery, portal vein and hepatic vein) and biliary structures. In this context, we introduced the utilization of simplified arterial microsuture techniques, which make the performance of arterial anastomoses much easier and more practical 4 and the precise utilization of arterial grafts 5, which allows for progressively better results in terms of arterial complications. Moreover, the utilization of a Rex shunt (i.e., a bypass between the superior mesenteric vein and the portal vein left branch) in cases of portal thrombosis 6 and technical modification of the hepatic vein anastomosis procedure, which involves the creation of a wide opening in the anterior wall of the inferior vena cava 7, have been responsible for a decrease in the rate of venous complications. However, biliary complications and size mismatches remain unsolved problems and are thus the subjects of important experimental studies. A weaning rat model of selective biliary obstruction was developed in our laboratory, with the aim of improving our understanding of biliary cirrhosis in cases of intrahepatic segmental biliary stenosis 8,9. Moreover, the consequences of engrafting liver grafts that are disproportionately large relative to the recipients' size, i.e., cases of infant recipients who are less than 5 kg in size, have not been completely elucidated. Therefore, we created a new swine “large-for-size” liver transplantation model 10 and many studies that have tentatively clarified the molecular and flowmetric mechanisms of lesions in this situation 11 as well as therapeutic measures to attenuate such lesions have been reported 11. Finally, the immunologic mechanisms involved in the humoral and cellular rejection of solid organ transplants remain a matter of continuing research in the literature. Despite all of the advances in immunosuppressive regimens and the development of accurate drugs with fewer collateral effects, acute and chronic rejections remain dreaded complications of pediatric liver transplantation. The diagnoses of acute and chronic rejection are based on histopathological findings, and portal inflammation and centrilobular necrosis are characteristics of acute rejection. Moreover, biliary duct paucity in the portal space and foam cell arteriopathy are the main aspects of chronic rejection 12. Regarding acute cellular rejection, treatment and management are relatively standardized and most cases exhibit good responses to corticosteroid bolus treatments as well as tacrolimus level adjustment 13. The treatment and evolution of pediatric patients with chronic rejection are not well characterized, as few published studies are present in the literature. Indeed, the mechanisms of chronic rejection are not completely known and the progressive biliary duct paucity may not respond to increased immunosuppression, which can lead to severe liver dysfunction, a need for retransplantation or death, as discussed in the paper by Tannuri et al. in the current issue of Clinics. Finally, the early histological findings and histological aspects that are suggestive of irreversibility must be defined, and prognostic factors after chronic rejection is diagnosed must be identified, although certain investigations have previously tried to identify the risk factors for the development of chronic rejection following liver transplantation in pediatric 14 and adult 15,16 populations. In conclusion, liver transplantation is a relatively new procedure that allows for the survival of many infants and children who otherwise would die. However, this procedure also results in a number of conditions and complications that have never been previously recognized and treated. Therefore, much remains to be studied and accomplished, particularly in the field of immunology.

Twenty-five years have passed since the first lung transplant was performed at the Instituto do Coracao (INCOR) do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. On October 16th, 1990, a 26-year-old woman with severe pulmonary fibrosis and secondary pulmonary hypertension underwent a single left lung transplant but only survived for 12 days, dying due to sepsis and diffuse alveolar damage. This occurred several months after the first and second 1 lung transplants in Brazil and seven years after the first in the world, which had been performed by Dr. Cooper in Toronto 2. Over a five-year period, nine more cases were performed, with the longest post-operative survival being 4 years. Despite the dedication of all the personnel involved with the program at that time, seven patients were never discharged due to acute respiratory failure and infection. At present, primary graft dysfunction remains a complication of transplant procedures, but in 1995, it seemed an almost insurmountable barrier. Despite the strong desire to continue performing this procedure, the group was not adequately prepared to continue in this field and the program was discontinued. In parallel, pulmonologists and surgeons sought training at other lung transplant centers and research in the field was initiated at our laboratory in the Medical School. Because bronchial healing remained a problem in clinical cases, it was chosen as a starting point for research. Using animal models of bronchial anastomosis and lung transplant as well as an established methodology for the evaluation of airway mucous clearance, the effect of immunosuppressive drugs was tested. Cyclosporin 3,5, Prednisone 6,7, Micophenolate 8 and combined therapies, including Tacrolimus 9,10, were tested and all drugs had a negative impact on mucous clearance. On August 9th 2000, a single right lung transplant was performed on a 32-year-old male with silicosis. The post-operative period was uneventful and the patient is still alive fifteen years later. The main problems concerning intraoperative care, post-operative care and immunosuppression seemed to be solved. However, in the following three years we performed ten more procedures, of which only two patients survived for more than one year. Although only two patients of this period are still alive, the low survival rate indicated that there was still something lacking. At that time, the current knowledge and infrastructure were considered sufficient, but it was clear that unless a dedicated team was established, we could not proceed in this field. In 2003, a multi-professional and multi-disciplinary team was formed that included pulmonologists, surgeons, infectologists, nurses, physiotherapists, nutritionists, social workers and psychologists. We established a routine of morning rounds in ICU and on the wards; assessment meetings; scientific meetings and journal clubs. Based on candidate selection criteria established by the International Society for Heart and Lung Transplantation, patients considered for LTx were assessed and visited by all members of the lung transplant team. Inclusion on a waiting list was possible only upon the agreement of all members of the staff. Since then, almost 250 procedures have been performed, including some landmark procedures: the first bilateral procedure in 2003, the first pediatric transplant in 2006, the first split transplant in 2011 and the first transplant using the ex vivo lung perfusion (EVLP) technique in 2012. However, some problems persisted. Initially, simple preoperative monitoring and patient positioning were problematic and each transplant presented individualized challenges, illustrating the difficulties inherent in establishing routines in the operating room. However, over time, the program has achieved consistently satisfactory results and survival in line with international rates (Figure 1). For diseases such as cystic fibrosis, the survival to the end of the first year is over 90%, even higher than the ISHLT Resistries 11. Approximately 35 procedures are performed annually in the State of Sao Paulo - a modest number compared to the number of patients on the waiting list, which impacts on the mortality rate of patients on the list. The main reason for the low number of transplants performed is the low success rate of lungs obtained from multiorgan donors. It is estimated that only 5% of available lungs are used, a very low frequency compared to the average rate of 15% reported by the UNOS 12. The main reason for the low utilization is the quality of the available lungs, which are rejected more than 50% of the time due to infection or inadequate management resulting in loss of lung function 13. Figure 1 Kaplan-Meier Survival Curve of LTx patients. One year survival: 65.6%, Five years survival: 55.3% and Ten years survival: 43.7%. Improving the quality of available donor lungs seemed to be the best solution for increasing the number of transplants. Thus, the first report on the reconditioning of initially rejected donor lungs by ex vivo perfusion 14 presented a solution for this problem. In 2007 we began preparations for EVLP via training courses and experimental studies with lungs rejected for transplantation. We initially sought to establish our methodology 15,16, then tested lung preservation solutions 17 and static or continuous topical preservation methodologies 18. This prepared us to perform the first lung transplantation using EVLP in Brazil in 2012. Three years after the procedure, the first patient is doing well. However, the cost and quality of using EVLP donor tissue in our country, and as a result, other transplants have not been performed with this technique. New research has been implemented in this area that incorporated the use of broad spectrum antibiotics during EVLP 19 and in trachea transplantation 20,21. Two important issues remaining are the training of personnel and international recognition. All staff members were trained in our institution and completed the training in transplant centers in North America or Europe. The Ministry of Health has certified InCor for medical residency in pulmonary and surgical transplantation, as well as two years of training in a clinical or surgical fellowship in lung transplantation certified by the Ministry of Education. We are internationally recognized as a part of the ISHLT registry and we actively participate in international congresses as members of the society and through the submission of scientific papers. Institutional support is fundamental for the maintenance of staff and we were supported without fail throughout the formation of the transplant group. Although the number of transplants performed every month remains small, the need of these patients for care is intense. Thus, maintaining a professional team on a full-time basis will only be feasible with professional development and salary adjustments. In 2013, the Transplant Center Unit of InCor was created, which relies on a 24/7 nursing team fully dedicated to procuring thoracic organs and mediating and enhancing the work of the transplant teams, resulting in the realization of 98 transplants in 2014, including adult and pediatric heart transplants and lung transplants. The road traveled thus far has enabled the formation of an accomplished group and national leadership in this area. It is essential that the foundations of our group are the same as those of universities: care, teaching and research. We believe that we have achieved these goals, but much remains to be accomplished in this field.