Neonatal screening for spinal muscular atrophy: A pilot study in Brazil.

Spinal muscular atrophy (SMA) is considered one of the most common autosomal recessive disorders, with an estimated incidence of 1 in 10,000 live births. Testing for SMA has been recommended for inclusion in neonatal screening (NBS) panels since there are several therapies available and there is evidence of greater efficacy when introduced in the pre/early symptomatic phases. In Brazil, the National Neonatal Screening Program tests for six diseases, with a new law issued in 2021 stating that it should incorporate more diseases, including SMA. In the present study, dried blood spot (DBS) samples collected by the Reference Services of Neonatal Screening of RS and SP, to perform the conventional test were also screened for SMA, using real-time PCR, with SALSA MC002 technique. A total of 40,000 samples were analyzed, enabling the identification of four positive cases of SMA, that were confirmed by MLPA. Considering our sampling, Brazil seems to have an incidence comparable to the described in other regions. This work demonstrated that the use of the MC002 technique in samples routinely collected for the conventional NBS program is suitable to screen for SMA in our conditions and can be included in the expansion of the neonatal screening programs.

Association of parental cardiovascular risk factors with offspring type 1 diabetes mellitus insulin sensitivity.

AIM: This study aimed to determine whether the insulin resistance (IR) and lipid profiles in Type 1 Diabetes (T1D) offspring are associated with IR and other cardiovascular risk factors in their parents. METHODS: This study included 99 T1D patients (19.6 ± 4.0 yrs.), 85 mothers and 60 fathers. Parents' IR was assessed by HOMA-IR, and the insulin sensitivity in T1D patients was assessed by the estimated Glucose Disposal Rate (eGDR). RESULTS: The eGDR in the T1D offspring was negatively related to age (p = 0.023), weight (p = 0.004), LDL (p = 0.026), and microalbuminuria (p = 0.019). Maternal Type 2 Diabetes (p < 0.001) and HOMA-IR (p = 0.029) were negatively related to eGDR in their T1D offspring. The maternal HOMA-IR and the proband's eGDR were positively (p = 0.012) and negatively (p = 0.042) associated with the birth weight of the T1D offspring, respectively. We didn't find an association with the fathers' profiles. CONCLUSIONS: In a cohort of offspring with T1D the insulin sensitivity was related to the IR, lipid profile, and the presence of T2D only in their mothers. Precocious screening and treatment of these risk factors beyond glycemic control will benefit T1D with this background.

Insulin lispro low mixture twice daily vs basal insulin glargine once daily and prandial insulin lispro once daily as insulin intensification strategies in patients with type 2 diabetes: Latin American subpopulation analysis of a randomized trial.

BACKGROUND: This post hoc analysis examined the efficacy and safety of twice-daily insulin lispro low mixture (LM25) and once-daily basal insulin glargine plus once-daily prandial insulin lispro (IGL) in a Latin American subpopulation with type 2 diabetes mellitus (T2DM). METHODS: A phase 4, randomized, open-label, parallel-arm trial included participants aged 18-75 years with T2DM taking once-daily insulin glargine and stable doses of metformin and/or pioglitazone with glycated hemoglobin (HbA1c) 7.5-10.5 % and fasting plasma glucose ≤121 mg/dL. Participants were randomized 1:1 to receive their stable dose of metformin and/or pioglitazone plus twice-daily LM25 or IGL for 24 weeks. The primary efficacy outcome was change in HbA1c after 24 weeks of treatment. Results from participants in Argentina, Brazil, and Mexico are presented here. RESULTS: 162 participants (80 LM25; 82 IGL) with mean ± standard deviation (SD) age = 57.3 ± 9.0 years and body mass index = 31.3 ± 5.2 kg/m(2) were included. Mean ± SD change in HbA1c from baseline to week 24 was -1.5 ± 1.0 % (LM25) and -1.1 ± 1.2 % (IGL). At week 24, 35.1 % (LM25) and 31.6 % (IGL) of participants achieved HbA1c <7.0 %. Mean ± SD weight gain from baseline to week 24 was 2.4 ± 2.9 kg in the LM25 group and 1.0 ± 3.1 kg in the IGL group. The mean ± SD rates of total hypoglycemia per year were 18.9 ± 27.3 (LM25) and 21.6 ± 31.1 (IGL). Rates of treatment-emergent adverse events were 46 % (LM25) and 39 % (IGL). CONCLUSIONS: Our results suggest that both LM25 and IGL are viable treatment options for insulin intensification in Latin American patients with T2DM with suboptimal glycemic control on basal insulin glargine. The safety and tolerability profiles of LM25 and IGL are consistent between this Latin American population and the global trial-level population. Trial registration NCT01175824.

Challenges associated with insulin therapy progression among patients with type 2 diabetes: Latin American MOSAIc study baseline data.

BACKGROUND: Poor glycemic control in patients with type 2 diabetes is commonly recorded worldwide; Latin America (LA) is not an exception. Barriers to intensifying insulin therapy and which barriers are most likely to negatively impact outcomes are not completely known. The objective was to identify barriers to insulin progression in individuals with type 2 diabetes mellitus (T2DM) in LA countries (Mexico, Brazil, and Argentina). METHODS: MOSAIc is a multinational, non-interventional, prospective, observational study aiming to identify the patient-, physician-, and healthcare-based factors affecting insulin intensification. Eligible patients were ≥18 years, had T2DM, and were treated with insulin for ≥3 months with/without oral antidiabetic drugs (OADs). Demographic, clinical, and psychosocial data were collected at baseline and regular intervals during the 24-month follow-up period. This paper however, focuses on baseline data analysis. The association between glycated hemoglobin (HbA1c) and selected covariates was assessed. RESULTS: A trend toward a higher level of HbA1c was observed in the LA versus non-LA population (8.40 ± 2.79 versus 8.18 ± 2.28; p ≤ 0.069). Significant differences were observed in clinical parameters, treatment patterns, and patient-reported outcomes in LA compared with the rest of the cohorts and between Mexico, Brazil, and Argentina. Higher number of insulin injections and lower number of OADs were used, whereas a lower level of knowledge and a higher level of diabetes-related distress were reported in LA. Covariates associated with HbA1c levels included age (-0.0129; p < 0.0001), number of OADs (0.0835; p = 0.0264), higher education level (-0.2261; p = 0.0101), healthy diet (-0.0555; p = 0.0083), self-monitoring blood glucose (-0.0512; p = 0.0033), hurried communication style in the process of care (0.1295; p = 0.0208), number of insulin injections (0.1616; p = 0.0088), adherence (-0.1939; p ≤ 0.0104), and not filling insulin prescription due to associated cost (0.2651; p = 0.0198). CONCLUSION: MOSAIc baseline data showed that insulin intensification in LA is not optimal and identified several conditions that significantly affect attaining appropriate HbA1c values. Tailored public health strategies, including education, should be developed to overcome such barriers. Trial Registration NCT01400971.

HDL cholesterol levels and weight are the main determinants of subclinical atherosclerosis in the young with type 1 diabetes and suitable glycaemic control.

The aim of this study was to evaluate subclinical atherosclerosis and related factors in young type 1 diabetes (T1D) patients and healthy peers. Carotid intima-media thickness (cIMT) and anthropometric/laboratorial data were obtained for 83 T1D patients (mean age 19.5 ± 4.0 years, disease duration 9.8 ± 4.8 years) and for 36 matched healthy subjects. Considering all the participants as one group, male sex (p = 0.008), weight (p = 0.016) and T1D (p < 0.001) were positively associated with a higher cIMT. High-density lipoprotein (HDL) (p = 0.036) was negatively associated with cIMT in T1D. In the male T1D patients, HDL ≤47.5 mg/dL had a sensitivity of 87.5% and specificity of 57% (p = 0.035) in detecting those belonging to a higher cIMT tercile. In conclusion, weight and T1D were associated with increased cIMT. HDL levels ≤47.5 mg/dL were related to a higher cIMT in male T1D patients.

The effects of discontinuing long term alendronate therapy in a clinical practice setting.

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7%) in G1 and one (5.2%) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

The effects of discontinuing long term alendronate therapy in a clinical practice setting / Efeitos da retirada do uso prolongado de alendronato na prática clínica

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7 percent) in G1 and one (5.2 percent) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

OBJETIVO: Avaliar a evolução dos marcadores de metabolismo ósseo (MMO) e da densidade mineral óssea (DMO) após cinco anos de uso de alendronato em mulheres osteoporóticas na pós-menopausa. SUJEITOS E MÉTODOS: 40 pacientes (pct) osteoporóticas, na pós-menopausa, em uso de alendronato (10 mg/dia) por pelo menos 5 anos (Grupo 1 − G1) tiveram o uso do bisfosfonato suspenso. O grupo 2 (G2): 25 mulheres na pós-menopausa, em uso de alendronato (10 mg/dia) há pelo menos 1 ano. Grupo 3 (G3): 23 pct osteoporóticas, controles ainda sem tratamento. G1 e G2 submeteram-se à avaliação da DMO por DXA (basal e após 12 meses de seguimento). Todas as pct colheram amostras basais de CTX e P1NP, e G1 e G2 submeteram-se a coletas trimestrais de CTX e P1NP durante 1 ano. Resultados foram analisados por ANOVA on ranks e Mann-Whitney. RESULTADOS: Níveis médios de DMO não variaram em G1 ou G2 durante o estudo; no entanto, 16 pct (45,7 por cento) no G1 e 1 pct (5,2 por cento) no G2 apresentaram redução clinicamente significativa de DMO (P < 0,001). Níveis basais de CTX e P1NP não diferiram entre G1 e G2, com ambos inferiores aos níveis de G3. Em G1, observou-se elevação significativa de CTX e P1NP após 3 meses. Os níveis de CTX e P1NP em G2 permaneceram estáveis durante todo o seguimento. CONCLUSÃO: Não parece haver supressão excessiva do metabolismo ósseo na prática clínica. A suspensão temporária do alendronato após seu uso prolongado pode não ser segura.

[Olfactory groove schwannoma: case report]. / Schwannoma da goteira olfatória: relato de caso.

Intracranial schwannoma not related to cranial nerves are unusual and rarely found in the subfrontal region. We report a case of olfactory groove schwannoma in a 27-year-old male, who presented with anosmia and headache initiated one year ago. At admission, bilateral papilledema was noted with absense of motor deficits or cranial nerves abnormalities. Cranial computed tomography (CT) revealed a bifrontal multicystic isodense enhancing mass lesion causing a frontal ventricular horn compression. Radiological features resembled that of a cystic olfactory groove meningioma. Decompressive bifrontal craniotomy was done. One month later, CT demonstrated a homogeneously contrast-enhancing mass in the olfactory groove region who extended into the left nasal cavity. Magnetic resonance imaging did not add more informations. A second surgical procedure was done through a nasoethmoidal approach with incomplete resection of the lesion. The complete tumor resection was only possible in a third surgery through another bifrontal approach. The hystopathological diagnosis of schwannoma was performed by conventional methods and confirmed by immunohistoquemical staining for S-100 protein. The rarity of this tumor and his clinical, radiological and histological aspects justify this publication.

Schwannoma da goteira olfatória. Relato de caso / Olfactory groove schwannoma: case report

Schwannomas intracranianos näo associados a nervos cranianos säo incomuns e raramente encontrados na regiäo subfrontal. Apresentamos raro caso de schwannoma da goteira olfatória, acometendo paciente de 27 anos, masculino, com quadro iniciado há 1 ano com perda da olfaçäo e cefaléia. Ao exame de admissäo, apresentava papiledema bilateral e anosmia. Tomografia computadorizada de Cranio (TC) revelou processo expansivo bifrontal hipodenso ao parênquima, com aspecto multicístico, sem captaçäo do contraste iodado, promovendo compressäo dos cornos ventriculares frontais. Os achados radiológicos sugeriam meningeoma cístico da goteira olfatória. Foi submetido a craniotomia frontal para descompressäo. Um mês após, TC de controle revelou processo expansivo da regiäo da goteira olfatória homogeneamente captante do contraste iodado, que se estendia para o interior da cavidade nasal esquerda. RM näo adicionou novas informações. Foi realizado segundo procedimento cirúrgico por via naso-etmoidal, com ressecçäo incompleta da lesäo. A ressecçäo completa foi possível através de re-operaçäo por craniotomia bifrontobasal. O diagnóstico histopatológico de schwannoma foi realizado através de microscopia óptica convencional e confirmado por técnica de imuno-histoquímica, utilizando o anticorpo para proteína S-100. A raridade deste tumor, seus aspectos clínicos, radiológicos e histológicos justificam esta publicaçäo

Metástase de meningeoma para linfonodos cervicais / Metastatic meningioma to cervical lymph nodes

Os autores relatam um caso de menongeoma atípico da goteira olfatória, acometendo um paciente de 74 anos, do sexo masculino, apresentado-se com quadro de hipertensão intracraniana e confusão mental. Após exérese cirúrgica, hove recidiva local precoce e matástase ganglionar cervical. As metástases extracranianas de meningeomas intracarnianos já foram bem documentadas, mas são raramente encontradas. Ocorre em menos de 0,1 por cento desses tumores. Os locais mais comuns dessas metástases são os pulmöes (60 por cento), o fígado (34 por cento), os linfonodos cervicais (18 por cento), os ossos longos, a pélvis e o crânio (11 por cento).