Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).

BACKGROUND: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC. PATIENTS AND METHODS: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment naive advanced TC. They received ramucirumab, carboplatin and paclitaxel for 6 cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was ORR according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were PFS, OS and safety. Centralized radiologic review was performed. RESULTS: From 11/2018 to 06/2023, 52 patients were screened, 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. ECOG PS was 0 in 68.5%, 1 in 31.4% patients. At the present analysis carried out some months later the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95%CI 63.1-91.6]. At the centralized radiological review of 33/35 evaluable patients, ORR was 57.6% [95%CI 39.2-74.5]. After a median follow-up of 31.6 months, median PFS was 18.1 [95%CI 10.8-52.3] and median OS 43.8 [95%CI 31.9-NR] months. Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE≥G3. CONCLUSIONS: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC.

Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP).

Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.

Returning to care after incarceration with HIV: the French Guianese experience.

BACKGROUND: HIV prevalence in correctional facilities may be 2 to 10 times higher than in the general adult population. Antiretroviral therapy (ART) interruption is frequent after an incarceration. This, in combination with post-release high-risk behaviors, may have detrimental consequences on the epidemic. Although return to care after release from correctional facilities has been described in many North American settings, data from South America seemed scarce. French Guiana is the only French territory located in South America. In 2014, HIV prevalence was estimated at 1.2% among pregnant women and oscillated around 4% in the only correctional facility. METHOD: HIV-infected adults released from the French Guiana correctional facility between 2007 and 2013 were included in a retrospective cohort survey. The first objective was to describe the cascade of care in the 4 years following release. The secondary objectives were to describe contacts with care and to identify factors associated with return to HIV care, 1 year after release. RESULTS: We included 147 people, mostly males (81.6%). The median time before the first ambulatory consultation was 1.8 months. Within 1 year after release, 27.9% came for unscheduled emergency consultations, 22.4% were hospitalized. Within 4 years after release, 40.0-46.5% were in care, 22.4% archieved virological success. Being on ART when incarcerated was associated with HIV care (aIRR: 2.0, CI: 1.2-3.0), whereas being HIV-diagnosed during the last incarceration was associated with poor follow-up (aIRR: 0.3, CI: 0.1-0.9). CONCLUSION: The risk of HIV-follow-up interruption is high, after an incarceration with HIV. ART supply should be sufficient to cover the timespan following release, several months if possible. Those not on ART at the time of incarceration may require special attention, especially those newly HIV-diagnosed while in custody. Comprehensive programs are necessary to support ex-offenders to stay on ART after incarceration.

Correlation between the body mass index of patients with breast cancer before and after chemotherapy.

The objective of this work was to show how the influence of the microenvironment in tumor cells and consequently the onset and tumor progression is becoming increasingly more evident. Cancer is the second leading cause of death in the developed world, surpassed only by heart disease and obesity, and is increasingly recognised as an oncogenic factor in the genesis of this tumor. Inflammatory me- diators related to obesity are suspected to play a role in oncogenic modification of substrates metabolism of nutrients, most patients diagnosed with breast cancer underwent chemotherapy treatment, and this may be an aggravating factor of obesity. The authors selected 49 patients with previous diagnosis of breast cancer who had undergone chemotherapy and evaluated data regarding body mass index (BMI) before and after chemotherapy. They observed that there was statistical difference of BMI of patients before and after chemotherapy with p = 0.03. Comparing the groups, a statistical difference was found between overweight and obesity grade II and overweight and obesity grade III. Patients with a diagnosis of breast cancer usually showed on average a BMI 27.84, worsening after chemotherapy to 28.64. These findings can help to accelerate the division and cell reproduction, because obesity is a risk factor for breast cancer, and weight gain seems to be a major factor after treatment and may influence the prognosis of these women.

Increased rates of local complication of central venous catheters in the targeted anticancer therapy era: a 2-year retrospective analysis.

PURPOSE: Totally implantable central venous accesses (port-a-cath) are often used for chemotherapy administration or prolonged intravenous infusions in cancer patients. Local and systemic complications may occur both during and after placement of port-a-cath despite the well-established techniques for its placement and care. Out of other catheter-related local complications, thrombosis and infections represent the most common. Complications related to central venous catheter may be associated with infusion of both conventional chemotherapy and molecularly targeted therapy. Incidence and nature of complications of central venous catheter have been well established for long-term chemotherapy. However, very sparse data exists on the incidence of complications of molecularly targeted therapies administered through a central venous catheter. Hence, we decided to retrospectively analyze the local complications of a central venous catheter in patients receiving molecularly targeted therapy and conventional chemotherapy, respectively. METHODS: Over a 2-year period, 459 devices were placed in two academic Italian institutions. Patients' characteristics, catheter-related complications, and their relationship with targeted therapy administration were retrospectively assessed. RESULTS: Catheter-related complications occurred in 30 out of the 459 analyzed cancer patients (7 %). Local complications occurred in 12 (40 %) and 18 (60 %) patients receiving standard chemotherapy and biological drugs, respectively. Eighteen (72 %) out of 25 patients developing biological complications (BC) were receiving biological drugs. Infusion of a biological drug through a central venous catheter has been shown to increase the risk of central venous catheter complications (p = 0.02). No difference between the incidence of complication between anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents was observed in our study despite the statistically significant early development of port-a-cath complication in the anti-EGFR group. Treatment with a biological drug and the stage of disease, in univariate analysis, had independent effect on the duration for development of catheter-related complications. CONCLUSIONS: Molecularly targeted therapy may influence the occurrence of BCs, i.e., infection and dehiscence. Onset of BCs occurred earlier in patients receiving biological drugs (more frequently with bevacizumab than with anti-EGFR therapy) than those undergoing traditional chemotherapy. Further studies are needed to ascertain the findings of our study and to elucidate the reason for the higher incidence of catheter-related complications.

[Risk of Infection Following Implant of Artificial Penile Nodule, Bouglous or Dominos: A Case Report in French Guiana]. / Risques d'infection suite à l'implant de nodules péniens bouglous ou dominos : à propos d'un cas en Guyane française.

Implant of artificial penile nodule (APN) is a socio-cultural practice, linked to penitentiary environment in French Guiana. Physicians are often unfamiliar with its existence. Although serious complications remain low regarding the high prevalence of this practice, urgent cares could be required. Indeed, implant of nodule can have functional sequelae, and sometimes life-threatening consequences, especially if infection occurs and spreads. We have reported the case of a 23-year-old male who presented an infection of the penis after the implant of two APN. Removal of the nodules associated with oral antibiotics was needed. We also present CT-scan images of another patient, as an example of fortuitous discovery of these nodules. We finally discuss the various complications already described in literature.

Le port de nodules péniens artificiels (NPA) est fortement lié à la fréquentation du milieu carcéral en Guyane française. Cette pratique est peu connue des professionnels de santé. Bien que les complications restent peu fréquentes malgré la prévalence élevée de ces nodules dans certaines populations, elles peuvent nécessiter une prise en charge diagnostique et thérapeutique urgente. En effet, il existe des risques fonctionnels, mais également vitaux survenant dans les suites d'une complication notamment infectieuse. Nous rapportons ici le cas d'une infection de la verge suite à l'implant de deux NPA chez un patient de 23 ans, pour laquelle le retrait des nodules et une antibiothérapie orale ont été nécessaires. Preuve de la forte prévalence de cette pratique, nous illustrons à l'aide d'une iconographie radiologique originale le cas d'un autre patient chez qui ces nodules ont été fortuitement découverts. Enfin, nous discutons des différentes complications décrites dans la littérature.

Merkel cell carcinoma in a renal transplant patient.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer which seems to be common in transplant recipients. We describe the case of a renal transplant patient who developed a MCC on the right glutaeus eight years after transplantation.

Mucocutaneous paraneoplastic syndromes (MCPS). A clinical-pathologic review.

Mucocutaneous paraneoplastic syndromes (MCPS) are a common group of dermatoses exhibiting a variable morphologic and pathologic picture which can occur in association with solid tumors or hematologic malignancies. In this review the Authors report the most important clinical characteristics and commonly associated malignancies of these dermatoses. Their identification is important because their superficial appearance and precocious arising are useful in the early diagnosis of an otherwise asymptomatic visceral malignancy and because differential diagnosis between skin metastases and malignancy-associated dermatoses is very important for a careful staging and management of the neoplasm. At the same time, MCPS may also be suggestive of the specific type of cancer present. Finally, the presence of a MCPS often carries grave oncologic implications. Once, therefore, the diagnosis of these dermatoses has been established, either an appropriate evaluation for an asymptomatic neoplasm in a cancer-free individual or an investigation for the recurrence of malignancy in an oncologic patient should be initiated.

[Similarities and differences in the color choice of patients under life-prolonging therapy and of healthy subjects]. / Analogie e differenze nella scelta dei colori tra soggetti in trattamento life-extending e soggetti sani.

The hypothesis of probable differences between subjects under life-extending treatment and healthy people was tested by applying the Lüscher Colour test to 2 groups of patients, one under dialysis, the other cardiopathic pacemaker wearers, and comparing them with a control group of healthy subjects. The results partly confirm the hypothesis and also show a further differentiation between the dialysis and pace-maker groups. A support programme using relaxation techniques (autogenous training and/or hypnosis) to balance and reduce problems revealed is therefore proposed.

[Autogenic training as a complementary therapy in unstable arterial hypertension in chronic uremics under periodic dialysis]. / Il training autogeno come terapia complementare nell'ipertensione arteriosa instabile dell'uremico cronico in dialisi periodica.

Consideration of the precarious mental balance of chronic uraemic patients receiving periodic haemodialysis, which often affects arterial pressure, led to a group of such patients being subjected to additional treatment in the form of Autogenous Training (A.T.). Comparison of some parameters such as arterial pressure and ECG's evaluated before and after A.T. shows, in several cases, a noticeable clinical improvement. It also has a definite tranquillising effect on the general anxiety state, which makes for better and longer-lasting adaptation to periodic dialysis. In the light of these results, Autogenous Training is proposed as a complementary treatment system for obviating certain non-physiological aspects of dialysis.

[Indices of disease activity in systemic lupus erythematosus. Review of the literature]. / Indici di attività di malattia nel Lupus Eritematoso Sistemico. Revisione critica della letteratura.

Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the production of autoantibodies reacting with many different self antigens. The analysis of clinical expression and evolution of this disease is a milestone in the definition of therapeutic strategies. A parameter universally accepted as gold standard is lacking so far. About 60 indices for defining and measuring the activity of this disease have been proposed in the last 20 years. The most important of these are discussed in this review, focusing both on their role in the evaluation and outcome of patients and on the main studies assessing their validity and reliability.

[Paraneoplastic syndromes of the central nervous system]. / Sindromi paraneoplastiche del sistema nervoso centrale.

Paraneoplastic syndromes of central nervous system are rare neurologic syndromes caused by cancer but not secondary to metastases. The physiopathologic mechanisms underlying these syndromes are still under debate. We report the biological and clinical features of the most frequent paraneoplastic syndromes involving the central nervous system. Their early clinical identification might be an useful marker of an otherwise unknown visceral malignancy. Furthermore, they might also be suggestive for the particular type of cancer present. Once, therefore, the diagnosis of these paraneoplastic syndromes has been established, an appropriate evaluation for the asymptomatic neoplasm in cancer-free individuals or investigation for the malignancy recurrences in oncologic patients might be performed.

Effect of the carbon oxidation level of the energy source on heat of reaction in biosynthesis of a Pseudomonas strain.

The heats of reaction for cell biosynthesis of a strain of Pseudomonas aeruginosa grown on ammonium-nitrogen and fumarate or butyrate as carbon-energy sources have been determined by microcalorimetric experiments, CO2 and molar growth yield determinations. The different oxidation level of the fumarate-carbon (C1+) and butyrate-carbon (C1-) caused a difference on the sign of the heat of reaction for cellular biosynthesis: positive for fumarate (delta H less than 0) and negative for butyrate (delta H greater than 0). It has been possible to state the stoichiometry of the biosynthetic reaction for fumarate only and not for butyrate because of the large pigment production under the experimental conditions adopted: pure oxygen as gas phase at 30 degrees C.

Parenteral iron supplementation for the treatment of iron deficiency anemia in children.

Iron-deficiency anemia impairs growth and intellectual development in children, which can be reversed only by early diagnosis and iron supplementation. Oral supplementation can efficiently replace stores, but in many cases parenteral iron is needed. Unfortunately some adverse reactions have limited its use in children. We compared the efficacy and safety of intramuscular and intravenous administration in 33 evaluable children with severe iron deficiency and/or iron-deficiency anemia who failed to respond to oral iron supplementation. Nineteen children received intravenous infusion and 14 intramuscular injections. All children showed recovery from iron-deficiency anemia, with statistically similar improvement in hemoglobin levels. The duration of treatment was longer in those receiving intramuscular injection. Parenteral iron therapy for the treatment of iron-deficiency anemia is a rapid, easy, and definitive solution to a long-troubling situation. We suggest the use of parenteral iron, in particular intravenous iron, in children who do not recover from severe iron-deficiency anemia after oral therapy. We should consider the physical and neuropsychological sequelae of long-lasting iron deficiency in children and the fact that oral supplementation is less likely to replace iron stores.

Polyclonal hypergammaglobulinemia at the onset of acute myeloid leukemia in children.

Polyclonal hypergammaglobulinemia (PHG) associated with hematological malignancies is a rare occurrence. We reviewed our series of 47 children with AML in order to define the prevalence of PHG and its prognostic value in achieving complete remission (CR) after induction treatment. Patients were stratified by immunoglobulin levels into two groups: with PHG and without PHG. CR reached after induction chemotherapy was considered a positive response. Conditional exact tests were used for the statistical analysis; conditional maximum likelihood estimates of the odds ratio (OR) were obtained. Significance levels (p) were determined from two-tailed tests. Twenty-two of 38 (57.9%) evaluable children showed PHG. Children with PHG and AML were more likely to be in CR after first induction treatment (OR=6.25, p=0.021), independent of sex, age at diagnosis, white blood cell count, percentage of blasts in the bone marrow, FAB phenotype, and treatment protocol. Infections seemed to positively influence early treatment response (p=0.038). PHG and infections were not statistically associated (p=0.16). PHG may result from the uncontrolled stimulation of B lymphocytes by cytokines. Infections or transfusions may act as triggers for the immune system, leading to the antileukemic effect seen in patients with AML and PHG going into spontaneous remission. It could be that this activation caused the larger number of CRs observed in our series. Clarification of why PHG exerts a positive influence on children with AML could help us to understand the ways by which the organism is able to control a malignant disease.

Comparison of the measurement of surface or total platelet-associated IgG in the diagnosis of immune thrombocytopenia.

Platelet-associated IgG (PAIgG) can be measured on intact platelets or following platelet lysis. Measurement of PAIgG following platelet lysis may provide different or additional information compared to PAIgG measured on intact platelets. The PAIgG of lysed platelets represents "total" PAIgG, ie, IgG on the surface of platelets plus any IgG that was inside the platelet. To investigate the clinical relevance of the two types of PAIgG assay we performed a prospective study on washed platelets collected from 47 patients with idiopathic thrombocytopenic purpura (ITP). The PAIgG was measured on intact and lysed platelets using an immunoradiometric assay. Platelet-associated IgG was 2-3 times higher when measured on lysed platelets from healthy controls or patients with ITP compared to PAIgG measured on the same intact platelets. The higher level of PAIgG observed following platelet lysis was not due to the reactions not achieving equilibrium. Using lysed platelets, PAIgG was elevated on 29 of 47 samples from different ITP patients and elevated in 31 samples when measured on intact platelets. The PAIgG is invariably higher when measured following platelet lysis compared measurements made on intact platelets. Neither technique offers a diagnostic advantage over the other.