Identifying and managing CAR T-cell-mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team.

INTRODUCTION: Chimeric antigen receptor (CAR)-T-cell therapy is a new treatment for patients with hematologic malignancies in which other therapies have failed. AREAS COVERED: The review provides an overview for recognizing and managing the most acute toxicities related to CAR-T cells. EXPERT OPINION: The development of immune-mediated toxicities is a common challenge of CAR-T therapy. The mechanism that determines this toxicity is still unclear, although an unfavorable tumor microenvironment and a pro-inflammatory state put patients at risk. The monitoring, diagnosis, and treatment of post-CAR-T toxicities must be determined and based on international guidelines and internal clinical practice. It is urgent to identify biomarkers that can identify patients at greater risk of developing complications. The adoption of consistent grading criteria is necessary to improve toxicity management strategies continually. The first-line therapy consists of supportive care and treatment with tocilizumab or corticosteroids. An early start of cytokine blockade therapies could mitigate toxicity. The plan will include cytokine release prophylaxis, a risk-adapted treatment, prevention of on-target/off-tumor effect, and a switch on/off CAR-T approach.

Netupitant/palonosetron without dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving high-dose melphalan for autologous stem cell transplantation: a single-center experience.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT.

The Burden in Caregivers of Multiple Myeloma Patients Undergoing Outpatient Autologous Stem-Cell Transplantation Compared to Inpatient Transplantation.

BACKGROUND: The application of different models of autologous stem-cell transplantation (ASCT) in multiple myeloma has demonstrated the feasibility and safety of outpatient-based programs of care. Although several systematic reviews have evaluated the burden of caregivers, only a few studies have included outpatient ASCT. PATIENTS AND METHODS: The feelings of lack of family support, daily activities, and general health were compared between caregivers of 2 groups of patients with multiple myeloma who underwent inpatient (n = 71) or outpatient (n = 25) ASCT. RESULTS: The 3 features did not significantly differ between the 2 study groups at baseline, before, and 3 months after ASCT. Multivariate modeling showed that the baseline values were significantly related to the changes in study outcomes independent of patient and caregiver characteristics. Other correlates were caregivers' work and patient age for impact on daily activities and disease burden across time for impact on general health (all P < .05). CONCLUSION: The outpatient model neither improves nor impairs global caregivers' burden compared to standard ASCT care. Further research is needed to confirm this observation and to better assess the burden and quality of life of caregivers and their influence on patient outcomes and quality of life.

Bacterial canker on kiwifruit in Italy: anatomical changes in the wood and in the primary infection sites.

The bacterial canker of kiwifruit caused by Pseudomonas syringae pv. actinidiae is a severe threat to kiwifruit production worldwide. Many aspects of P. syringae pv. actinidiae biology and epidemiology still require in-depth investigation. The infection by and spread of P. syringae pv. actinidiae in xylem and phloem was investigated by carrying out artificial inoculation experiments with histological and dendrochronological analyses of naturally diseased plants in Italy. We found that the bacterium can infect host plants by entering natural openings and lesions. In naturally infected kiwifruit plants, P. syringae pv. actinidiae is present in the lenticels as well as in the dead phloem tissue beneath the lenticels, surrounded by a lesion in the periderm which appears to indicate the importance of lenticels to kiwifruit infection. Biofilm formation was observed outside and inside plants. In cases of advanced stages of P. syringae pv. actinidiae infection, neuroses of the phloem occur, which are followed by cambial dieback and most likely by infection of the xylem. Anatomical changes in wood such as reduced ring width, a drastic reduction in vessel size, and the presence of tyloses were observed within several infected sites. In the field, these changes occur only a year after the first leaf symptoms are observed suggesting a significant time lapse between primary and secondary symptoms. It was possible to study the temporal development of P. syringae pv. actinidiae-induced cambial dieback by applying dendrochronology methods which revealed that cambial dieback occurs only during the growing season.

Artroplastia unicompartimental do joelho no tratamento da osteonecrose primária do côndilo femoral medial / Unicompartmental knee arthroplasty for the treatment of medial femoral condyle primary osteonecrosis

Os autores estudaram a evolução de 15 pacientes portadores de osteonecrose primária do côndilo femoral medial do joelho em fase avançada, submetidos à artroplastia unicompartimental, com dois tipos de prótese. Baseados na análise feita segundo escores da International Knee Society pré e pós-operatórios, concluem que a artroplastia unicompartimental é uma boa alternativa para o tratamento da osteonecrose unicompartimental do joelho

Tratamento das fraturas complexas da diáfise femoral com "interlocking nail" / Treatment of complex fractures of the shalf with interlocking nail

Foram operados 14 casos de fratura de fêmur com pino travado do tipo Grosse-Kempf. Destes, seis eram fraturas expostas, 12 eram fraturas do tipo IV e dois do tipo II, de acordo com a classificação de Winquist. Observamos a consolidação clínica e radiológica em todos os casos, com média de 14,3 semanas e retarde de consolidação (maior que seis meses) em dois casos. Não foram observados infecção, desvio rotacional ou encurtamento superior a 1 cm em nenhumcaso. Constatamos desvio em varo em dois casos, em que a cortical medial estava fraturada. O período médio de internação pós-operatória foi de três dias. A amplitude média de flexão do joelho foi de 125 graus. Concluímos ser este um método eficiente para o tratamento deste tipo de fratura.

Estudo do tratamento cirúrgico das lesöes graves de joelho envolvendo o ligamento cruzado posterior / Study of the surgical treatment of severe lesions of the knee with posterior cruciate ligament

Os autores estudaram 31 casos de pacientes atendidos ao período de 1982 a 1994, com lesoes graves e ruptura do ligamento cruzado posterior (LCP). Foram divididos em dois grupos conforme o tipo de tratamento cirúrgico: grupo I, lesao de LCP por avulsao de fragmento ósseo (três casos); grupo II, lesao intersticial do LCP; IIA, reparaçao isolada do LCP (11 casos); IIB, reparaçao do LCP, e reforço com tendao do músculo semitendineo (oito casos); IIC, reconstruçao do LCP com enxerto autólogo de tendao patelar (seis casos). Os pacientes foram avaliados observando-se critérios subjetivos e objetivos e, pelos resultados, sao discutidos a indicaçao dos tratamentos cirúrgicos e seus prognósticos.

Como fixamos o enxerto de tendäo patelar na substituiçäo dos ligamentos cruzados do joelho / Fixating the patellar tendon graft to replace cruciate ligaments of the knee

Os autores estudaram em laboratório os métodos de fixaçäo do enxerto de tendäo patelar na substituiçäo do ligamento cruzado anterior, independente da via de acesso cirúrgico. Seus resultados permitiram concluir que a fixaçäo do enxerto por meio de fios de Ethibond n§ 5 ou aço n§ 2 säo equivalentes em termos de resistência à traçäo, uma vez que as falha se däo através do tecido ósseo. Em relaçäo ao número e posicionamento dos fios, verificou-se que dois fios conferem resistência suficiente à fixaçäo sem comprometer a resistência do segmento ósseo do enxerto; e que o posicionamento de um fio "a cavaleiro", na transiçäo osso-tendäo, näo é adequado, por conferir menor resistência ao conjunto. Finalmente, a fixaçäo por meio de fios de Ethibond n§5 ancorados em parafusos corticais à tibia e fêmur foi comparada à fixaçäo por meio de parafuso de interferência, tendo os dois métodos mostrado resistência equivalente à traçäo longitudinal