Terapi Sistemik Terkini Pada Karsinoma Sel Ginjal Metastatik

Kurang lebih sepertiga pasien dengan karsinoma sel ginjal (KSG) telah mengalami metastasis pada saat pertama kali didiagnosis dan 40-50% akan mengalami metastasis jauh setelah diagnosis awal. Karsinoma sel ginjal resistan terhadap sebagian besar kemoterapi dan obat sitotoksik konvensional. Namun demikian, selama beberapa tahun terakhir pengobatan kanker ini menunjukkan kemajuan yang spektakuler karena berkembangnyatargeted therapybagi karsinoma sel ginjal metastatik (KSGm). Tujuan dari penulisan makalah ini adalah untuk menelaah tata laksana terkini KSGm. Hingga saat ini, terdapat enam obat yang telah disetujui oleh FDA dan beberapa asosiasi urologi Internasional untuk digunakan sebagai terapi KSGm lini pertama dan kedua. Lini pertama terdiri dari sunitinib (progression-free survival, PFS, 11 bulan dibandingkan dengan 5 bulan pada IFN-?, danoverall survival, OS, 26,4 bulan dibandingkan dengan 21,8 bulan pada IFN-?), kombinasi bevacizumab dan IFN-? (PFS 10,2 bulan dibandingkan dengan 5,4 bulan pada kombinasi plasebo dan IFN-?, OS 23,3 bulan dibandingkan dengan 21,3 bulan pada kombinasi plasebo dan IFN- ?), pazopanib (PFS 9,2 bulan dibandingkan dengan 4,2 bulan pada plasebo), serta temsirolimus (OS 10,9 bulan dibandingkan dengan 7,3 bulan pada IFN-?), sedangkan lini kedua terdiri dari sorafenib (PFS 5,5 bulan dibandingkan dengan 2,8 bulan pada plasebo) dan everolimus (PFS 4,0 bulan dibandingkan dengan 1,9 bulan pada plasebo).Katakunci: Karsinoma sel ginjal metastatik terapi target, terapi sistemi

The dose makes the poison: A case report of acquired methemoglobinemia

Background: Methemoglobinemia (MET) should be suspected in cases where cyanosis is not associated with signs and symptoms of lung and/or heart disease, or in a cyanotic child exhibiting discrepancies in the partial pressure of oxygen in the arterial blood, the blood oxygen saturation, and the clinical assessment. Case presentation: A 10-month-old girl was taken to the Pediatric Emergency Department for the acute, sudden development of significant peroral cyanosis associated with gray pigmentation of the skin. The problem was evidenced approximately one hour after she ingested a homemade puree of mixed vegetables, mainly composed of potatoes and chards that had been prepared three days before and had been kept in the refrigerator since then. Physical examination revealed that the child was very pale, conscious, and without respiratory distress. Oxygen saturation of hemoglobin in the arterial blood (SpO2) was 94%. Respiratory, cardiovascular, and abdominal evaluations did not reveal any signs of disease. A venous blood sample showed chocolate-colored blood with a pH of 7.404, a partial pressure of CO2 (pCO2) of 40.6 mmHg, a partial pressure of oxygen (pO2) of 21.3 mmHg, a bicarbonate level of 24 mmol/L, and an oxygen saturation (SO2%) of 47.7%. CO-oximetry carried out simultaneously identified a methemoglobin level of 22%. MET was suspected, and oxygen via nasal cannula at a rate of 4 L/min was given with only a slight increase in oxygen saturation (96%). Slow intravenous injection of methylene blue 1 mg/kg over a period of 5 minutes was initiated. The peripheral oxygen saturation (SpO2) gradually improved to 100% over the next 20 minutes. Forty minutes later, venous blood gas analysis showed a methemoglobin level of 0.9% with a complete resolution of cyanosis; supplemental oxygen via nasal cannula was therefore discontinued. During the next 36 hours, the patient remained hemodynamically stable with good oxygenation on room air. Conclusions: This case report shows that recognition of acquired MET in a child with sudden cyanosis onset requires a high index of suspicion. In daily activities, there is a need to pay particular attention when homemade vegetable soups for child alimentation are prepared. The consumption of vegetable soups must occur immediately after preparation. Storage in a refrigerator must last no more than 24 hours and if longer storage is needed, vegetable soups should be frozen

Nocardiosis in a Kidney-Pancreas Transplant

34-year-old man with chronic renal and pancreas failure in complicated diabetic disease received a kidney-pancreas transplantation. On the 32nd postoperative day, an acute kidney rejection occurred and resolved with OKT3 therapy. The patient also presented refractory urinary infection by E. Fecalis and M. Morganii, and a focal bronchopneumonia in the right-basal lobe resolved with elective chemotherapy. During the 50th post-operative day, an intense soft tissue inflammation localized in the first left metatarsal-phalangeal articulation occurred (Figure 1) followed by an abscess with a cutaneous fistula and extension to the almost totality of foot area. The radiological exam revealed a small osteo-lacunar image localized in the proximal phalanx head of the first finger foot. From the cultural examination of the purulent material, N. Asteroides was identified. An amoxicillin-based treatment was started and continued for three months, with the complete resolution of infection This case is reported for its rarity in our casuistry, and for its difficult differential diagnosis with other potentially serious infections

Estimation of peptide concentration by a modified bicinchoninic acid assay

Although biuret based protein assays are theoretically applicable to peptide measurement, there is a high level of inter-peptide variation, determined largely by peptide hydrophobicity. This variation in peptide reactivity can be significantly reduced by heat-denaturation of peptides at 95 °C for 5 minutes in the presence of 0.1 M NaOH containing 1% (w/v) SDS, prior to incubation for 30 min at 37 °C in BCA standard working reagent. This modification to the standard bicinchoninic acid (BCA) assay protocol allows for an accurate, rapid and economical estimation of the peptide concentration within an unknown sample

Home management of children with COVID-19 in the Emilia-Romagna region, Italy

In most children, coronavirus disease 2019 (COVID-19) is a mild or moderate disease. Moreover, in a relevant number of cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains totally asymptomatic. All these findings seem to suggest that otherwise healthy children with suspected COVID-19 might be managed in the community in most cases, thus avoiding hospital admission and closely related medical, social and economic problems, including overwhelming hospitals. Unfortunately, home management of children with suspected COVID-19 rarely occurs, and many children with suspected or laboratory-confirmed SARS-CoV-2 infection are frequently hospitalized irrespective of the severity of disease. To evaluate the role of community health houses (CHHs) in the management of children with COVID-19, 1,009 children with suspected SARS-CoV-2 infection were studied in Emilia-Romagna Region, Italy. Among them, 194 (19.2%) resulted positive for SARS-CoV-2. The majority (583, 58%) were tested at home by CHHs, while 426 (42%) were brought to the hospital for testing. The patients who were managed in the hospital had a significantly lower median age than those who were managed at home (2 vs. 12 years, p < 0.001). Exposure to SARS-CoV-2 cases within the family was significantly more frequent among those who were managed at home (82 vs. 46%, p < 0.05). The clinical findings were similar between the children who were managed at home and those who were managed in the hospital. Only one of the children managed at home (0.7%) required hospitalization; in comparison, 26 (48%) of those whose swab samples were taken at the hospital were hospitalized. Our research shows for the first time the importance of CHHs in the management of COVID-19 in children; because of the high frequency of mild to moderate cases, management by CHHs can reduce the care load in hospitals, providing enormous advantages on the familial, medical, social, and economic levels. These findings could be useful for suggesting a territorial rather than hospital-based strategy in pediatrics in the case of a new wave of the epidemic

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Combined antiretroviral therapy reduces hyperimmunoglobulinemia in HIV-1 infected children

Objective: To evaluate the effect of combined antiretroviral therapy on serum immunoglobulin (Ig) levels in HIV-1 perinatally infected children. Methods: Data from 1250 children recorded by the Italian Register for HIV Infection in Children from 1985 to 2002 were analysed. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using means and standard deviations of normal population for each age period. Combined antiretroviral therapy has become widespread in Italy since 1996, thus differences in Ig z-scores between the periods 1985-1995 and 1996-2002 were analysed. Data according to type of therapeutic regimen were also analysed. Results: Between the two periods 1985-1995 and 1996-2002, significant (P < 0.0001) decreases in IgG (6.29 ± 4.72 versus 4.44 ± 4.33), IgM (9.25 ± 13.32 versus 5.61 ± 7.93), and IgA (10.25 ± 15.68 versus 6.48 ± 11.56) z-scores, together with a parallel significant (P < 0.0001) increase in CD4 T-lymphocyte percentages, were found. These decreases were confirmed regardless of whether the children were receiving intravenous Ig or not. Ig z-scores were significantly higher in children receiving mono-therapy than in those receiving double-combined therapy (IgC, P < 0.0001; IgM, P = 0.003; IgA, P = 0.031) and in the latter children than in those receiving three or more drugs (P < 0.0001 for all z-scores). Ig z-scores correlated inversely with CD4 T-lymphocyte percentages and, directly, with viral loads. Conclusions: Our data show that in HIV-1 infected children combined antiretroviral therapy leads to reduction of hyperimmunoglobulinemia which parallels restoration of CD4 T-lymphocyte percentage and viral load decrease, which it turn probably reflects improved B-lymphocyte functions. © 2004 Lippincott Williams & Wilkins