Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a “converter phenotype,” which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies.Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed.Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected.Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

The Effect of COVID-19 Vaccination on Reducing the Risk of Infection, Hospitalization, and Death in Isfahan Province, Iran

Background: We aimed to evaluate the effect of COVID-19 vaccines in preventing infection, hospitalization, and mortality due to COVID-19 in Isfahan Province, Iran. Methods: Following a retrospective cohort design, data of all vaccinated individuals since the rollout of vaccination of the general population are analyzed, Mar 2020 to Aug 13, 2021. Moreover, the data of all non-vaccinated people were collected by the census method for this period. The two groups were compared concerning hospitalization and mortality using the Chi-square test. Kaplan-Meyer was also used to calculate the median interval between receiving a vaccine and outcome (hospitalization and death). Results: Overall, 583434 people have received a second dose of a vaccine from Mar 2020 to Aug 2021, which 74% (n=433403) was Sinopharm, 18.2% (n=106027) AstraZeneca, 3.6% (n=21216) Sputnik, and 3.9% (n=22,788) Barekat. In contrast, 2,551,140 people living in the Isfahan Province did not receive a vaccine. The median interval between injection of the first dose and the hospitalization for those who received Sinopharm, AstraZeneca, Sputnik, and Barekat was 22, 61, 19, and 19 days, respectively. For unvaccinated cases, the rates of infection, hospitalization, and mortality (per 1000 population) were 69.7, 12.1, and 1.04, respectively. In contrast, for vaccinated individuals, these rates were 3.9, 1.08, and 0.09, two weeks after the second dose, respectively. Conclusion: The highest and lowest reduction in relative risk was for those who received AstraZeneca and Sputnik, respectively.

Developing a Screening Procedure During the COVID-19 Pandemic: Process and Challenges Faced by a Low-Incidence Area

Purpose: To summarize the imaging results of COVID-19 pneumonia and develop a computerized tomography (CT) screening procedure for patients at our institution with malignant tumors.Methods: Following epidemiological investigation, 1,429 patients preparing to undergo anti-tumor-treatment underwent CT scans between February 17 and April 16, 2020. When CT findings showed suspected COVID-19 pneumonia after the supervisor radiologist and the thoracic experience radiologist had double-read the initial CT images, radiologists would report the result to our hospital infection control staff. Further necessary examinations, including the RT-PCR test, in the assigned hospital was strongly recommended for patients with positive CT results. The CT examination room would perform sterilization for 30 min to 1 h. If the negative results of any suspected COVID-19 pneumonia CT findings were identified, the radiologists would upload the results to our Hospital Information Systems and inform clinicians within 2 h.Results: Fifty (0.35%, 50/1,429) suspected pneumonia cases, including 29 males and 21 females (median age: 59.5 years old; age range 27–79 years), were identified. A total of 34.0% (17/50) of the patients had a history of lung cancer and 54.0 (27/50) underwent chemotherapy or targeted therapy. Forty-six patients (92.0%) had prior CT scans, and 35 patients (76.1%) with suspected pneumonia were newly seen (median interval time: 62 days). Sub-pleura small patchy or strip-like lesions most likely due to fibrosis or hypostatic pneumonia and cluster of nodular lesions were the two main signs of suspected cases on CT images (34, 68.0%). Twenty-seven patients (54.0%) had, at least once, follow-up CT scan (median interval time: 18.0 days). Only one patient had an increase in size (interval time: 8 days), the immediately RT-PCR test result was negative.Conclusion: CT may be useful as a screening tool for COVID-19 based on imaging features. But the differential diagnosis between COVID-19 and other pulmonary infection and/or non-infectious disease is very difficult due to its overlapping imaging features.The confirmed diagnosis of the COVID-19 infection should be based on the etiologic eventually. The cancer patients at a low-incidence area would continue treatment by screening carefully before admission.

Evaluation of Cumulative Effect of Standard Triple Immunosuppression on Prevention of De Novo Donor Specific Antibodies (dnDSA) Production in Children after Kidney Transplantation—A Retrospective and Prospective Study

De novo Donor Specific Antibodies (dnDSA) are associated with inferior graft outcomes. Standard immunosuppression is expected to prevent dnDSA production in low-risk patients. We have evaluated a cumulative effect of a triple immunosuppression (CNI/MMF/Pred), as well as TAC concentration and coefficient of variation on the incidence of dnDSA production. Overall, 67 transplanted patients were evaluated in retrospective (dnDSA for-cause; n = 29) and prospective (dnDSA by protocol; n = 38) groups. In the retrospective group, the eGFR value at first dnDSA detection (median interval—4.0 years post-transplant) was 41 mL/min/1.73 m2; 55% of patients presented biopsy-proven cAMR, and 41% lost the graft within next 2.4 years. Patients from the prospective group presented 97% graft survival and eGFR of 76 mL/min/1.73 m2 at 2 years follow-up, an overall incidence of 21% of dnDSA and 18% of acute (T cell) rejection. None of the patients from the prospective group developed cAMR. Median value of Vasudev score within 2 years of follow-up was not significantly higher in dsDSA negative patients, while median value of TAC C0 > 1–24 months post-transplant was 7.9 in dnDSA negative vs. 7.1 ng/mL in dnDSA positive patients (p = 0.008). Conclusion: dnDSA-negative patients presented a higher exposure to tacrolimus, while not to the combined immunosuppression.

Network Oncolgy Specialist Advisory Service – A Survey of the Psychosocial Situation of Long Term Cancer Survivors During Childhood or Adolescents

Background The number of long term cancer survivors during childhood or adolescence is increasing steadily. Survivors often suffer from physical or psychosocial long term effects. There is currently little data on the arrangement of long term aftercare in the field of psychosocial care. Methods In November 2017 a questionnaire was sent to 1900 cancer survivors aged between 18 and 35 years whose diagnosis dated at least five years prior. The obtained data serve as a condition and needs assessment, how the (psychosocial) long-term aftercare is perceived by the survivors and what else is desired. The analysis was conducted using descriptive statistics as well as the calculation of bivariate correlations. Results The response rate was 54.9% (n=1.043). The median interval from the first diagnosis was 20 years. In total 666 survivors (63.9%) stated that they suffered from at least one long term effect. Within this, especially neurocognitive themes played a role. 87.2% of the respondents had the feeling that they had overcome the illness/therapy well. Conclusion Through a stronger patient-focussed orientation concerning the current care and advisory services, the situation of long term survivors could be improved. This especially includes access to relevant information that focuses on the available psychosocial and welfare services, as well as to advisory and care services. Additionally, the development and expansion of care structures in the areas of neurocognition and psychotherapy is important to ensure long term participation attendance.

Extrusion of the distal ventriculoperitoneal shunt catheter through the umbilicus: a systematic literature review from 1973 to 2021

Trans-umbilical extrusion of the distal ventriculoperitoneal shunt catheter is a rare complication of the VPS insertion. The objectives of this review were to analyze various variables like the age, sex, indication for VPS insertion, clinical presentation, the operative therapy offered for the management, and outcome of the cases published/managed for the trans-umbilical extrusion of the distal VPS shunt catheter. In 1973, the maiden case of trans-umbilical extrusion of the distal VPS catheter was published. Literature/case reports were retrieved from 1973 to October 31, 2021. A total of n=24 (12 males, 12 females) cases were recruited for this systematic review. All of them were children below the age of 13-years. In four-fifths (n=19) of children, the initial VPS catheter was inserted during the first 6-months of life. The median age of children at the time of diagnosis of the above-described VPS complication was 7.5 (42.21 SD) months, and it ranged from 2 months to 13 years of age. The median interval from the initial VPS insertion/last VPS revision to the diagnosis of complication was 4 (24.77 SD) months, and it ranged from 3 weeks to 8 years. The main complaint was the extrusion of the distal VPS catheter through the umbilicus. Surgical procedures performed for the management were (a) removal of the entire VPS catheter n=15, (b) removal of distal/part of distal VPS catheter n=5, and (C) others n=2. For VPS catheter revision; delayed re-VPS insertion was performed in n=10, immediate revision of the distal VPS catheter in n=3, and others. Three (12.5%) children died during the postoperative and follow-up period. The distal VPS catheter extrusion through the umbilicus is a rare complication of VPS insertion, and it occurred exclusively in children. In 70% (n=17) of children, it was documented ≤6 months afterward of the VPS insertion. Delayed re-VPS catheter insertion was preferred for 40% of the children for VPS revision procedures.

Case series of scar endometriosis- post caeserean section: A diagnostic pitfall

The presence and growth of ectopic functional endometrial tissue outside the uterus is called endometriosis among which scar endometriosis is rare and difficult to diagnose. It occurs as a result of obstetrical and gynecological surgeries and can be confused with other surgical conditions. We reviewed the case records of patients with the diagnosis of scar endometriosis seen in our hospital from 2015 to 2018. We found six patients of scar endometriosis. The median age of the patients was 28.5 years (range 20-31 years) and median interval from symptoms to treatment was 4 years (range 2-6 years). Four patients had first presented to either the surgery or dermatology physicians. The most common complain being cyclical pain and swelling at local site. Patients underwent wide excision of the mass with no recurrence of symptoms at a follow up ranging from 9 months to 12 years. Confirmation of the diagnosis is histopathology with wide surgical excision being the treatment of choice. We have discussed the pathogenesis, diagnosis and treatment of this condition. Imaging techniques and FNAC are indicated towards better diagnostic approach and avoid confusion with other conditions. Medical treatment is helpful in selected cases only. After studying and presenting this paper we would like to highlight on such a rare condition and prevent its misdiagnosis.

Comparison of the characteristics and outcomes of traumatic wound dehiscence after penetrating or Lamellar Keratoplasty for Keratoconus

Purpose: To examine the incidence, causes, characteristics, and the visual outcome of traumatic wound dehiscence (TWD) after penetrating keratoplasty (PK) compared to lamellar keratoplasty (LKP) for keratoconus. Methods: The medical records of all keratoconus patients undergoing TWD repair after PK or LKP over a 7-year period at the King Khaled Eye Specialist Hospital (KKESH), Riyadh were reviewed. Data were collected on patient demographics, interval between keratoplasty and trauma, and characteristics and visual outcomes of TWD. Results: During January 2006 to December 2012, 2863 eyes in KKESH underwent PK. Another 1716 eyes underwent LKP. Of these, 55 (1.9%) and 30 (1.7%) sustained TWD, respectively ( p = 0.675). Approximately two-thirds of patients with traumatic wound dehiscence (TWD) were males in both groups (63.6% and 70.0%, respectively). The mean age at trauma was 24.6 ± 6.7 years (range 12–41 years) in the PK group compared with 22.6 ± 6.0 years (range 13–34 years) in the LKP group ( p = 0.166). The median interval between keratoplasty and trauma was 6.2 (the interquartile range (IQR), 10.9) months for the PK group and 4.6 (IQR, 7.4) months for the LKP group ( p = 0.116). At the last follow-up after wound repair, visual acuity was similar between the PK and LKP groups ( p = 0.595). Conclusion: In our study, the incidence of TWD after PK and LKP in patients with keratoconus was within the previously reported range of values. All patients undergoing these procedures, especially males, should receive adequate information regarding this lifelong risk, and the need for protective eye-wear and seeking early medical advice when complications occur.

Therapy-Related Acute Myeloid Leukemia (t-AML) and the Advantage of Intensive Chemotherapy: Real-Life Analysis from Two Regional French Centers

Rational: Patients with t-AML are those previously treated for primary malignancy and are categorized with poor prognosis. t-AML treatment options include intensive chemotherapy (IC), hypomethylating agents (HMA) or low dose cytarabine (LDC). However, survival remains poor and allogeneic hematopoietic cell transplantation (Allo-HCT) could lead to better outcomes. The aim of this analysis is to assess the outcome of all consecutive t-AML pts from two regional centers in France, based on treatment intensity, and to identify prognostic factors. Patients and Methods: between January 2006 and December 2019, 112 adult pts diagnosed with t-AML occurring after treatment of solid tumors (ST; n=72), hematologic malignancies (HM; n=34) or autoimmune diseases (AID; n=6). Pts received chemotherapy and/or radiotherapy or high dose chemotherapy followed by autologous hematopoietic cell transplantation (Auto-HCT) in some. All eligible t-AML pts received intensive chemotherapy (IC, n=55) with the combination of anthracycline and cytarabine in 48 pts and CPX-351 in 7 pts. Unfit pts received non-IC (9 LDC, 24 HMA). The third study group (24 pts) received best supportive care (BSC). Fifteen pts underwent HSCT in first CR. Statistical analysis: We performed a descriptive analysis of the baseline characteristics and each treatment group was compared with a Kruskal-Wallis test and a Pearson's Chi-square test. Survival curves (Kaplan-Meier method) were compared with a log-rank test. Univariate and multivariate analyses on survival, relapse and NRM were done using Cox regression, Gray test, Fine & Gray regression. The bilateral level of significance was set at 5%. All analyses and graphics were made under the R program (v3.5.1). A pair-matched control analysis with de novo AML was performed only on pts who received IC matched for age, cytogenetics and ELN 2010 classification. Results: A total of 112 t-AML pts were identified, 56 were males (50%) with a median age of 68 yrs (19-87) at t-AML diagnosis. Before t-AML, 72 pts had ST (64.5%), 34 HM (30.5%) and 6 AID (5%). Forty-six pts (41%) received chemotherapy alone for their primary cancer, 17 (15%) radiotherapy alone, 49 (44%) radio chemotherapy, 17 (15%) auto-HCT and 6 (5%) long-term methotrexate for AID. Median interval from treatment of previous ST or HM to t-AML diagnosis was 4.7 years in ST, 6.6 years in HM and 21 years in AID (p=0.03). At t-AML diagnosis, 42% of pts presented an unfavorable karyotype and 44% an unfavorable ELN 2010 classification. Regarding molecular alterations, FLT3-ITD, FLT3-TKD, NPM1 and IDH1/2 mutations were observed in 6.9, 2.3, 11.5 and 2.3% of pts respectively. MECOM1 was overexpressed in 25.5% of cases. Among treated pts (n=88), 43 pts (49%) achieved CR: 4 from 33 (12%) in non-IC pts (3 in HMA and 1 in LDC) and 39 from 55 (71%) in IC pts. Fifteen pts (17%) underwent Allo-HCT with a median interval between AML diagnosis and Allo-HCT of 4.7 mo (2.6-17.5). The best response after transplantation was CR in 10 pts; at the last follow up, 4 pts are alive (3 in CR and 1 in relapse) and 11 died (5 from relapse, 5 from TRM causes and 1 from another subsequent malignancy). Overall, with a median follow up of 5.5 mo (0-144), the median OS and DFS were 9 mo (5.9-13.5) and 6.3 mo (5.3-10.3) respectively (Figure). There was a significant difference between the 3 treatment groups concerning OS (p<0.001) and DFS (p<0.001) with a significant difference in OS between IC and non-IC groups (p=0.02). In the 88 treated t-AML pts, with a median follow up of 8.2 mo (0.3-144), the median OS was 13.5 mo (10.3-19.6) and the median DFS was 8.2 mo (7-13.7). Multivariate analysis for total and treated populations showed no impact of all variables related to previous malignancies except for auto-HCT pre-t-AML (significant negative impact on OS, DFS, NRM), WBC at t-AML diagnosis (negative impact on OS, DFS) and chemotherapy (positive in total population on OS, DFS, NRM and negative impact of IC on OS and NRM in treated pts) . In IC treated pts, we showed, in a pair-matched analysis with de novo AML, no difference in term of OS and DFS due to a significant higher CI of NRM (p=0.045) at 24 mo (40% in t-AML versus 27.4% for de novo AML) and a lower CI of relapse (NS) at 24 mo (33% in t-AML versus 47.6% for de novo AML). Conclusion: The prognosis of t-AML remains poor and our study showed the advantage of using intensive chemotherapy whenever possible and, in comparison with de-novo AML, a higher NRM and a lower incidence relapse. Figure 1 Figure 1. Disclosures Nicolini: Sun Pharma Ltd.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kartos Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses, Research Funding; Incyte Biosciences: Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; BMS: Honoraria.

Long-term cancer survivors treated with multiple courses of repeat radiation therapy

Introduction and background Through recent advances in cancer care, the number of long-term survivors has continuously increased. As a result, repetitive use of local radiotherapy for curative or palliative indications might have increased as well. This analysis aims to describe patterns of care and outcome of patients treated with multiple courses of repeat radiotherapy. Materials and methods All patients treated with radiotherapy between 2011 and 2019 at our department of Radiation Oncology were included into this analysis. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. Demographics, cancer and treatment characteristics and overall survival of patients having undergone multiple radiotherapy courses (minimum n = 5) were evaluated. Results The proportion of cancer patients treated with a minimum five courses of radiotherapy increased continuously from 0.9% in 2011 to 6.5% in 2019. In the 112 patients treated with a minimum of five radiotherapy courses, the primary tumor was lung in 41.9% (n = 47), malignant melanoma in 8.9% (n = 10) and breast in 8.0% (n = 9) of cases. A median interval of 3 years (maximum 8 years) elapsed between the first and the last radiotherapy course. The maximum number of courses in a single patient were n = 10. Treatment intent was curative or palliative in 46.4% and 53.6% for the first radiotherapy, respectively. The proportion of curative intent decreased to 11.6% at the 5th, and the last radiotherapy course was following a palliative intent in all patients. Five-year overall survival measured from the 1st radiotherapy course was 32.7%. Median overall survival was 3.3, 2.4, 1.3, and 0.6 years when measured from the 1st, the 1st palliative, the 5th and last course of radiotherapy, respectively. Discussion and conclusion A continuously increasing number of patients is treated with multiple courses of radiotherapy throughout their long-term cancer survivorship.