Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Abstract Background The distinction between sensory neuronopathies (SN), which is by definition purely sensory, and sensory polyneuropathies (SP) and sensory multineuropathies (SM) is important for etiologic investigation and prognosis estimation. However, this task is often challenging in clinical practice. We hypothesize that F-wave assessment might be helpful, since it is able to detect subtle signs of motor involvement, which are found in SP and SM, but not in SN. Objective The aim of the present study was to determine whether F-waves are useful to distinguish SN from SP and SM. Methods We selected 21 patients with SP (12 diabetes mellitus, 4 transthyretin familial amyloid polyneuropathy, 4 others), 22 with SM (22 leprosy), and 26 with SN (13 immune-mediated, 10 idiopathic, 3 others) according to clinical-electrophysiological-etiological criteria. For every subject, we collected data on height and performed 20 supramaximal distal stimuli in median, ulnar, peroneal, and tibial nerves, bilaterally, to record F-waves. Latencies (minimum and mean) and persistences were compared across groups using the Kruskal-Wallis and Bonferroni tests. P-values < 0.05 were considered significant. Results All groups were age, gender, and height-matched. Overall, there were no significant between-group differences regarding F-wave latencies. In contrast, F-wave persistence was able to stratify the groups. Peroneal F-wave persistence was higher, bilaterally, in the SN group compared to SM and SP (p < 0.05). In addition, F-waves persistence of the ulnar and tibial nerves was also helpful to separate SN from SP (p < 0.05). Conclusion F-wave persistence of the peroneal nerves might be an additional and useful diagnostic tool to differentiate peripheral sensory syndromes.

Resumo Antecedentes A distinção entre neuronopatias sensitivas (SN) e polineuropatias sensitivas (SP) e multineuropatias sensitivas (SM) é importante para a investigação etiológica e para o prognóstico. Contudo, esta tarefa é desafiadora na prática clínica. Hipotetizou-se que a avaliação das ondas-F pode ser útil, por ser capaz de detectar envolvimento motor nas SP e SM, mas não nas SN. Objetivo Determinar se as ondas-F podem ajudar a distinguir entre SN, SP e SM. Métodos Selecionou-se 21 pacientes com SP (12 diabetes mellitus, 4 ATTR-FAP e 4 com outras neuropatias), 22 com SM (22 hanseníases) e 26 com SN (13 imunomediadas, 10 idiopáticas e 3 com outras neuronopatias), de acordo com critérios clínicos, etiológicos e eletrofisiológicos. Para cada indivíduo, foi aferida a altura e foram aplicados 20 estímulos distais supramáximos nos nervos mediano, ulnar, fibular e tibial, bilateralmente, para registrar as ondas-F. Uma comparação foi feita, por grupo, das latências (mínimas e médias) e persistências pelos testes Kruskal-Wallis e Bonferroni. Valores de p < 0.05 foram considerados estatisticamente significativos. Resultados Todos os grupos foram pareados por idade, sexo e altura. Não houve diferença estatística significativa entre os grupos quanto às latências das ondas-F. A persistência da onda-F foi capaz de estratificar os grupos, sendo as dos nervos fibulares bilateralmente maiores no grupo SN que nos grupos SM e SP (p < 0.05). Adicionalmente, a persistência das ondas-F dos nervos ulnares e tibiais também foi útil para distinguir SN de SP (p < 0.05). Conclusão A persistência das ondas-F dos nervos fibulares pode ser uma ferramenta adicional e útil para diferenciar síndromes sensitivas periféricas.

Abstract Background: Livedoid vasculopathy (LV) manifests as ulcers and atrophic white scars on the lower extremities. The main known etiopathogenesis is hypercoagulability with thrombus formation, followed by inflammation. Thrombophilia, collagen and myeloproliferative diseases may induce LV, but the idiopathic (primary) form predominates. Bartonella spp. may cause intra-endothelial infection and skin manifestations caused by these bacteria may be diverse, including leukocytoclastic vasculitis and ulcers. Objective: The aim of this study was to investigate the presence of bacteremia by Bartonella spp. in patients with difficult-to-control chronic ulcers diagnosed as primary LV. Methods: Questionnaires and molecular tests (conventional PCR, nested PCR and real-time PCR) were applied and liquid and solid cultures were performed in the blood samples and blood clot of 16 LV patients and 32 healthy volunteers. Results: Bartonella henselae DNA was detected in 25% of LV patients and in 12.5% of control subjects but failed to reach statistically significant differences (p = 0.413). Study limitations: Due to the rarity of primary LV, the number of patients studied was small and there was greater exposure of the control group to risk factors for Bartonella spp. infection. Conclusion: Although there was no statistically significant difference between the groups, the DNA of B. henselae was detected in one of every four patients, which reinforces the need to investigate Bartonella spp. in patients with primary LV.

Abstract Leprosy reactions are an acute inflammatory phenomenon that can arise before diagnosis, during treatment, or after cure of leprosy. These reactions are considered one of the main diseases that cause physical disabilities. Immunosuppressive treatment for these immune responses makes these patients susceptible to coinfections, which can trigger new leprosy reactions. The main objective of this study was to evaluate the occurrence of infection by Bartonella sp. in blood samples from 47 patients who had untreatable episodes of type 2 leprosy reactions for more than six months, comparing them with a control group. Cultures and molecular methods (PCR) were used. Amplicons from species-specific reactions and sequencing showed a higher prevalence of Bartonella henselae infection in patients, 19/47 (40.4 %), compared to control, 9/50 (18.0 %), p= 0.0149. Five patients accepted treatment for coinfection, and all showed improvement in leprosy reactions with treatment for B. henselae infection. We conclude that these bacteria can trigger chronic reactions of type 2 leprosy and should be investigated in these patients. Summary line Patients who have chronic type 2 leprosy reactions are more susceptible to Bartonella henselae infection than controls: 19/47 (40.4 %) compared 9/50 (18.0 %), p= 0.0149.

ABSTRACT We report the case of a 6-year-old boy that presented with enlarged lymph nodes on his neck. He complained of tiredness and discouragement, which worsened during feverish periods. There were no relevant laboratory test abnormalities and serological tests were not reactive. Bartonella henselae DNA was detected by species-specific nested polymerase chain reaction. After treatment, the patient progressed with no fever or lymphadenopathy. Bartonellosis is a group of infectious diseases caused by bacteria of the genus Bartonella. This case report is a useful reminder to clinicians that long-term fever of unknown origin can be related to B. henselae infection, even if the specific serology is not reactive.

ABSTRACT As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.

ABSTRACT Bartonella spp. are re-emerging and neglected bacterial pathogens. The natural reservoirs for several species of this genus are domestic animals such as cats and dogs, the most common pets in the USA and Brazil. Some cat studies suggest that the infection is more prevalent in tropical and poverty-stricken areas. These bacteria were associated with a wide spectrum of clinical manifestations: fever of unknown origin, endocarditis, angiomatosis, chronic lymphadenopathy, hepatitis, fatigue, paresthesia and pain. Our group has already demonstrated that B. henselae -infected sickle cell disease mice present with hyperalgesia. We hypothesized that even immunocompetent mice infected by B. henselae would show an increased and persistent mechanical sensitivity. Five ten-week old male BALB/c mice were intraperitoneally inoculated with a 30 µL of suspension containing 10 4 CFU/mL of B. henselae, while five others were inoculated with an equal volume of saline solution. Four days after bacterial inoculation, the mechanical paw withdrawal threshold was measured using von Frey filaments in all animals, for five consecutive days. The infected animals showed hypersensitivity to mechanical stimuli for five consecutive days. The present study has demonstrated that B. henselae infection induces persistent mechanical hypersensitivity, a signal consistent with pain.

Abstract Bartonellosis are diseases caused by any kind of Bartonella species. The infection manifests as asymptomatic bacteremia to potentially fatal disorders. Many species are pathogenic to humans, but three are responsible for most clinical symptoms: Bartonella bacilliformis, Bartonella quintana, and Bartonella henselae. Peruvian wart, caused by B. bacilliformis, may be indistinguishable from bacillary angiomatosis caused by the other two species. Other cutaneous manifestations include maculo-papular rash in trench fever, papules or nodules in cat scratch disease, and vasculitis (often associated with endocarditis). In addition, febrile morbilliform rash, purpura, urticaria, erythema nodosum, erythema multiforme, erythema marginatus, granuloma annularis, leukocytoclastic vasculitis, granulomatous reactions, and angioproliferative reactions may occur. Considering the broad spectrum of infection and the potential complications associated with Bartonella spp., the infection should be considered by physicians more frequently among the differential diagnoses of idiopathic conditions. Health professionals and researchers often neglected this diseases.

RESUMO A inclusão, a adesão e o sucesso de estudantes de baixa renda na graduação são metas importantes no ensino superior brasileiro, assim como em outras partes do mundo, principalmente em cursos concorridos e em tempo integral, como o de Medicina. Este manuscrito analisa o desempenho de estudantes de graduação em Medicina, comparando dois grupos: os que se candidataram e receberam uma bolsa de estudos durante os anos acadêmicos (bolsistas) e os demais (sem bolsa). Analisamos dados de 417 estudantes de Medicina que se formaram entre 2010 e 2013, correspondendo a quatro anos de uma coorte retrospectiva, numa universidade pública gratuita no Brasil. A análise estatística foi realizada pelo teste exato de Fisher, o teste t de Student, o de Mann-Whitney e a regressão linear para comparar os escores desses grupos no sexto e décimo segundo semestres (meio e último semestres) e no exame de admissão para programas de residência médica, compostos por: escore total, teste de múltipla escolha para avaliação do conhecimento, avaliação clínica estruturada simulada, entrevista e perguntas escritas. A variável independente foi receber uma bolsa de estudos, enquanto as variáveis de controle foram idade, estratos socioeconômicos, gratificações extras para o ensino médio em instituição pública e autodeclaração de raça, pontuação no vestibular (geral e em cada área avaliada) e escolaridade dos pais. Um total de 243 alunos (58,2%) receberam uma bolsa de estudos, a maioria como bolsa de iniciação científica (217 ou 89,3%), enquanto 10,7% a receberam por assistência social. A renda média per capita foi cerca de 16% menor entre os bolsistas (p = 0,01) em comparação com aqueles que não receberam bolsa. Os estudantes bolsistas obtiveram melhor desempenho acadêmico no sexto (p<0,01) e no décimo segundo (p<0,01) semestres, mas não na admissão em programas de residência médica. O bom desempenho foi independentede idade,raça, recebimento de bônus à admissão na escola médica e formação educacional dos pais. Portanto, concluímos que receber uma bolsa na graduação foi associadoa melhor desempenho dos alunos durante o curso de graduação em Medicina. Enfatizamos a importância de reforçar programas semelhantes, especialmente para ajudar a apoiar os alunos mais vulneráveis socioeconomicamente.

ABSTRACT The inclusion, adherence and success of low-income undergraduates are important goals in Brazilian higher education, as well as in other parts of the world, especially in busy and full-time courses such as medicine. This paper analyzes the performance of undergraduate medical students by comparing two groups: those who applied for and received a scholarship during the academic years (scholarship holders) and the others (without scholarship). We analyzed data from 417 medical students who graduated between 2010 and 2013, corresponding to four years of a retrospective cohort at a free public university in Brazil. Statistical analysis was performed using Fisher’s exact test, Student’s t test, Mann-Whitney test, and linear regression to compare the scores of these groups in the sixth and twelfth semesters (middle and final semesters) and in the admission exam for medical residency programs, consisting of: total score, multiple choice test for knowledge assessment, simulated structured clinical assessment, interview and written questions. The independent variable was to receive a scholarship, while the control variables were age, socioeconomic strata, extra gratuities for high school in public institution and self-declaration of race, score in the vestibular entry exam (general and in each area assessed) and parents’ level of education. A total of 243 students (58.2%) received a scholarship, most of them as a scientific initiation grant (217 or 89.3%), while 10.7% received social assistance, the average income per capita was about 16% lower among students who received a scholarship (p = 0.01) compared to those who did not. Scholarship recipients achieved better academic performance in the sixth (p<0.01) and in the twelfth (p<0.01) semester, but not in admission to medical residency programs. Good performance was independent of age, race, receipt of bonuses for admission to medical school, and educational background of their parents. Therefore, we conclude that receiving a scholarship at the undergraduate level was associated tobetter student performance during the undergraduate medical course. It is important to emphasize the importance of reinforcing similar programs, especially to help support students who are most vulnerable socioeconomically.

ABSTRACT This study involves a 49-year-old male, who for three years suffered with a myelodysplastic syndrome and who needed frequent blood transfusions. One day following a transfusion, he presented fever and abdominal pain. The fever became persistent and only improved temporarily with two cycles of intravenous ciprofloxacin. Nearly 120 days after beginning the second cycle of treatment, he had experienced a weight loss of 16 kg and recurring fever. Screening for fever of unknown origin was conducted, including Bartonella infection. No etiology could be found. The patient improved with an antimicrobial regimen composed of oral doxycycline and intravenous ciprofloxacin. After 15 days afebrile, the patient was discharged with a four-month oral prescription of doxycycline and ciprofloxacin. Eight months following the antibiotic treatment, the patient received an allogeneic bone marrow transplant. Five days following the transplant, the patient initiated a febrile neutropenia and died. From a blood sample collected and stored at the time of hospitalization, a microbiological and molecular study was performed again. Blood- and liquid culture-PCRs from the same blood sample were all negative, but an isolate from solid subculture was found. The molecular reactions from this isolate were all positive and the sequence was 100% homologous to Bartonella henselae . The present report points to the limitations of laboratory techniques currently available for investigation of possible cases of bartonellosis in clinical practice, and the potential risk of Bartonella spp. transmission through blood transfusions.

A Faculdade de Ciências Médicas da Unicamp implantou uma ampla reforma curricular, que antecedeu as Diretrizes Curriculares Nacionais (DCN) de 2001. Analisou-se a trajetória profissional e o impacto da reforma curricular na formação pela percepção dos egressos. Alunos concluintes de 1991-2005 compuseram o grupo pré-reforma e os de 2006-2012, o grupo pós-reforma, que receberam um questionário semiestruturado on-line por e-mail e redes sociais. Obtiveram-se 213 (15,8%) respostas do grupo pré e 126 (16,1%) do pós-reforma. Os dados apontaram pouca dispersão geográfica dos ex-alunos, ocupação de 2,4 postos de trabalho por médico, entendimento da residência como necessária, maior frequência a cursinhos preparatórios no grupo pós-reforma e sugestão de inclusão de administração/gestão em saúde no currículo. A integração entre áreas básicas/clínicas apresentou significante melhora pós-reforma. A percepção sobre a graduação foi altamente positiva. O estudo contribuiu para implantar o acompanhamento sistemático de egressos no curso de Medicina.

The School of Medical Sciences of UNICAMP implemented a new curriculum in 2001, predating the national guidelines. This study analyzed the professional trajectory and the new curriculum’s impact. Graduates from 1991 to 2005 were grouped in the pre-curricular renovation group, and those from 2006 to 2012 in the post-group. A semi-structured survey was sent through e-mail and social media. There were 213 (15.8%) answers from pre-renovation group and 126 (16.1%) from post. Data showed low geographic dispersion of alumni, 2.4 work posts per physician, residency as a necessary complementation, suggestions for curricular inclusion of management issues and higher frequency of preparatory courses for residency in post-renovation group. There are signs of better integration between basic and clinical areas after the reform. Alumni showed positive perceptions regarding their undergraduate course. The study contributes to the implementation of systematic follow-up of graduates.

La Facultad de Ciencias Médicas de Unicamp implantó una amplia reforma curricular que antecedió a las directrices curriculares nacionales de 2001. Se analizó la trayectoria profesional y el impacto de la reforma curricular en la formación a partir de la percepción de los egresados. Alumnos concluyentes de la promoción 1991-2005 compusieron el grupo pre-reforma y los de 2006-2012 el grupo post-reforma, recibiendo un cuestionario semi-estructurado, on line, por e-mail y redes sociales. Se obtuvieron 213 (15,8%) respuestas del grupo pre-reforma y 126 (16,1%) del post-reforma. Se encontró poca dispersión geográfica de los ex-alumnos, ocupación de 2,4 puestos de trabajo/médico, comprensión de la residencia como necesaria, mayor frecuencia a cursos preparatorios en el grupo post-reforma y sugerencia de inclusión de administración/gestión en salud en el currículo. La integración entre áreas básicas/clínicas presentó una mejora significativa post-reforma. La percepción sobre la graduación fue altamente positiva. El estudio contribuyó para implantar el acompañamiento sistemático de egresados en el curso de Medicina.

A Faculdade de Ciências Médicas da Unicamp implantou uma ampla reforma curricular, que antecedeu as Diretrizes Curriculares Nacionais (DCN) de 2001. Analisou-se a trajetória profissional e o impacto da reforma curricular na formação pela percepção dos egressos. Alunos concluintes de 1991-2005 compuseram o grupo pré-reforma e os de 2006-2012, o grupo pós-reforma, que receberam um questionário semiestruturado on-line por e-mail e redes sociais. Obtiveram-se 213 (15,8%) respostas do grupo pré e 126 (16,1%) do pós-reforma. Os dados apontaram pouca dispersão geográfica dos ex-alunos, ocupação de 2,4 postos de trabalho por médico, entendimento da residência como necessária, maior frequência a cursinhos preparatórios no grupo pós-reforma e sugestão de inclusão de administração/gestão em saúde no currículo. A integração entre áreas básicas/clínicas apresentou significante melhora pós-reforma. A percepção sobre a graduação foi altamente positiva. O estudo contribuiu para implantar o acompanhamento sistemático de egressos no curso de Medicina.

The School of Medical Sciences of UNICAMP implemented a new curriculum in 2001, predating the national guidelines. This study analyzed the professional trajectory and the new curriculum’s impact. Graduates from 1991 to 2005 were grouped in the pre-curricular renovation group, and those from 2006 to 2012 in the post-group. A semi-structured survey was sent through e-mail and social media. There were 213 (15.8%) answers from pre-renovation group and 126 (16.1%) from post. Data showed low geographic dispersion of alumni, 2.4 work posts per physician, residency as a necessary complementation, suggestions for curricular inclusion of management issues and higher frequency of preparatory courses for residency in post-renovation group. There are signs of better integration between basic and clinical areas after the reform. Alumni showed positive perceptions regarding their undergraduate course. The study contributes to the implementation of systematic follow-up of graduates.

La Facultad de Ciencias Médicas de Unicamp implantó una amplia reforma curricular que antecedió a las directrices curriculares nacionales de 2001. Se analizó la trayectoria profesional y el impacto de la reforma curricular en la formación a partir de la percepción de los egresados. Alumnos concluyentes de la promoción 1991-2005 compusieron el grupo pre-reforma y los de 2006-2012 el grupo post-reforma, recibiendo un cuestionario semi-estructurado, on line, por e-mail y redes sociales. Se obtuvieron 213 (15,8%) respuestas del grupo pre-reforma y 126 (16,1%) del post-reforma. Se encontró poca dispersión geográfica de los ex-alumnos, ocupación de 2,4 puestos de trabajo/médico, comprensión de la residencia como necesaria, mayor frecuencia a cursos preparatorios en el grupo post-reforma y sugerencia de inclusión de administración/gestión en salud en el currículo. La integración entre áreas básicas/clínicas presentó una mejora significativa post-reforma. La percepción sobre la graduación fue altamente positiva. El estudio contribuyó para implantar el acompañamiento sistemático de egresados en el curso de Medicina.