Management of patients with HER2-positive metastatic breast cancer after trastuzumab deruxtecan failure.

The current treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) has been greatly impacted in the past decade by the introduction of antibody-drug conjugates (ADCs), which represent a relatively novel therapeutic class with the peculiar ability to deliver otherwise overtly toxic chemotherapeutics to tumor sites by exploiting the specificities of monoclonal antibodies. Indeed, drug engineering refinements in ADC design, such as through the introduction of cleavable linkers and hydrophobic payloads, resulted in improved patient outcomes in recent years. Two different ADCs, namely trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have already entered clinical practice for the treatment of HER2-positive ABC. In this scenario, T-DXd has shown to portend better survival outcomes compared to T-DM1, while leaving a large unsought area of unmet medical need upon T-DXd failure. Treatment decision and benefit of cancer drugs following T-DXd still represent an area of clinical controversy, where a preclinical investigation and clinical development should be prioritized. As the pace of innovation is currently accelerating, and with novel ADC formulations advancing in early-phase clinical trials, the whole BC field is changing at an unprecedented rate, with potential broadenings of therapeutic indications. In this review, we present the clinical landscape of HER2-positive advanced BC and discuss our vision on how to tackle T-DXd resistance, providing a perspective on the priority areas of the cancer research in this setting.

Seroconversion in patients with cancer and oncology health care workers infected by SARS-CoV-2.

BACKGROUND: Patients with cancer have high risk for severe complications and poor outcome to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease [coronavirus disease 2019 (COVID-19)]. Almost all subjects with COVID-19 develop anti-SARS-CoV-2 immunoglobulin G (IgG) within 3 weeks after infection. No data are available on the seroconversion rates of cancer patients and COVID-19. PATIENTS AND METHODS: We conducted a multicenter, observational, prospective study that enrolled (i) patients and oncology health professionals with SARS-CoV-2 infection confirmed by real-time RT-PCR assays on nasal/pharyngeal swab specimens; (ii) patients and oncology health professionals with clinical or radiological suspicious of infection by SARS-CoV-2; and (iii) patients with cancer who are considered at high risk for infection and eligible for active therapy and/or major surgery. All enrolled subjects were tested with the 2019-nCoV IgG/IgM Rapid Test Cassette, which is a qualitative membrane-based immunoassay for the detection of IgG and IgM antibodies to SARS-CoV-2. The aim of the study was to evaluate anti-SARS-CoV-2 seroconversion rate in patients with cancer and oncology health care professionals with confirmed or clinically suspected COVID-19. RESULTS: From 30 March 2020 to 11 May 2020, 166 subjects were enrolled in the study. Among them, cancer patients and health workers were 61 (36.7%) and 105 (63.3%), respectively. Overall, 86 subjects (51.8%) had confirmed SARS-CoV-2 diagnosis by RT-PCR testing on nasopharyngeal swab specimen, and 60 (36.2%) had a clinical suspicious of COVID-19. Median time from symptom onset (for cases not confirmed by RT-PCR) or RT-PCR confirmation to serum antibody test was 17 days (interquartile range 26). In the population with confirmed RT-PCR, 83.8% of cases were IgG positive. No difference in IgG positivity was observed between cancer patients and health workers (87.9% versus 80.5%; P = 0.39). CONCLUSIONS: Our data indicate that SARS-CoV-2-specific IgG antibody detection do not differ between cancer patients and healthy subjects.

Peer support groups in multiple sclerosis: current effectiveness and future directions.

Peer support programs have become a common method of providing support for patients with chronic illness. Utilizing peers as resources has been proposed as an effective means for coping with a stressful life experience and for gaining support from others who share a common factor, although data are somewhat mixed on the efficacy of peer support. The aim of the present study was to evaluate the effectiveness of eight weeks of a standard form of peer support in improving quality of life and reducing depressive symptoms in 44 patients with multiple sclerosis (MS). One person from each of six groups participated in a training course in order to learn basic principles of peer support. Eight weekly sessions were held and patients completed self-administered questionnaires pre- and post-treatment assessing quality of life and depression. Results showed that support groups do not provide consistent improvement in quality of life or depression in patients with MS and suggest that patients who have better mental health functioning could be at risk for deterioration in support groups.

The interdisciplinary approach to the treatment of multiple sclerosis patients in Italy: an aspiration or a reality?

The aim of the study was to assess whether the components necessary for an interdisciplinary approach to the treatment of multiple sclerosis (MS) patients exist in Italian MS clinics and to identify factors that make the difference between reality and aspiration for this type of approach. One hundred two out of 147 neurology departments with MS clinics throughout Italy compiled a questionnaire about characteristics and organizational structure of the clinic, type and number of professionals and resource needs. Eight hundred twenty-three healthcare professionals are currently working in MS clinics: 50% (412) neurologists, 28.7% (236) nurses, 15.1% (124) physical therapists, 3.4% (28) psychologists and 2.8% (23) social workers. Neurologists are evenly distributed between northern and southern parts of the country even though there are nearly double the number of patients followed in northern dinics compared to those in the south. Physicians reported themselves as most in need of continuing education, twice that which the same physicians reported for any other professional. The study has identified issues that contribute to the difficulty in developing and applying an interdisciplinary approach to providing care and services to Italian MS patients. Several factors have been delineated that require significant reshaping in order for this approach to begin to develop.

5,10-Methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension.

Hyperhomocyst(e)inemia is a known risk factor for the development of atherosclerotic vascular damage. Plasma homocyst(e)ine levels are influenced by nutritional and hereditary factors. A point mutation (cytosine to thymidine substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) makes the enzyme thermolabile and has been associated with elevated homocyst(e)ine levels in homozygous carriers (TT genotypes). We evaluated the relationship between the T allele encoding for the thermolabile variant of MTHFR and several biochemical risk factors and early signs of hypertensive and atherosclerotic organ damage in 206 untreated patients with primary hypertension. The MTHFR genotype was evaluated by polymerase chain reaction. Albuminuria was measured as albumin-to-creatinine ratio in three nonconsecutive first morning urine samples (negative urine culture). Persistent Mi (Alb+) was defined as an average albumin-to-creatinine ratio between 2.38 and 19 (men) and 2.96 and 20 (women). Left ventricular (LV) mass index (LVMI) was assessed by M-B mode echocardiography (LV hypertrophy, LVH = LVMI > or = 125 g/m2), carotid geometry by high-resolution ultrasound scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of Mi, LVH, and retinopathy was 14%, 45%, and 42%, respectively. The prevalence of carotid plaque was 25%. Allele frequencies for C (wild-type allele) and T allele (mutant allele) were 56% and 44%, respectively. Genotype frequencies were CC 29%, CT 54%, TT 17% according to Hardy Weinberg equilibrium. There were no differences as for age, sex, body mass index, blood pressure levels, lipid profile, smoking habits, and alcohol intake, and LVMI and urinary albumin excretion on the basis of MTHFR genotype. Patients with TT polymorphism showed a higher prevalence of retinal vascular changes (TT, 61% v CT + CC, 38%; P < .02) and carotid plaque (TT, 42% v CT + CC, 21%; P < .05) compared to patients with CC and CT polymorphism. Moreover, patients with T allele showed increased carotid artery size as demonstrated by intima plus media thickness (IT, 0.79 +/- 0.05 mm v CT + CC, 0.67 +/- 0.02 mm; P < .02), relative wall thickness (TT, 0.23 +/- 0.01 mm v CT + CC, 0.20 +/- 0.005 mm; P < .02), and surface area (TT, 19 +/- 1.9 mm2 v CT + CC, 15 +/- 0.55 mm2; P < .05). Multiple linear regression analysis demonstrated that MTHFR genotype and systolic blood pressure independently influence intima-media thickness and together account for about 11% of its variations (r2 = 0.11, F = 9.7, dF = 1-205, P < .0001). Homozygosity for the T allele of the MTHFR gene is an independent risk factor for the development of early atherosclerotic organ damage in hypertensive patients.

A cost evaluation of multiple sclerosis.

As a chronic and disabling disease, multiple sclerosis (MS) is extremely costly, both for the individual and the family, as well as for the society. Early onset, long duration and effects on employment contribute to the extensive costs related to the illness. Thus far, studies conducted in developed countries have demonstrated that direct costs, including treatment (prior to the approval of beta interferon), medical visits, hospitalization, assistance, etc., are much lower in respect to indirect costs, such as loss of income from reduction of work activity for patients and carers, which account for up to 75% of the total cost. Informal care represents a heavy burden for the families of disabled persons and little is known about the 'intangible' costs of MS, such as those related to the influence of the disease on quality of life. In addition, the cost/benefit ratio for expensive new therapies, such as beta interferon, remains to be determined.

Increased renal resistive index in patients with essential hypertension: a marker of target organ damage.

BACKGROUND: Increased renal resistance detected by ultrasound (US) Doppler has been reported in severe essential hypertension (EH) and recently was shown to correlate with the degree of renal impairment in hypertensive patients with chronic renal failure. However, the pathophysiological significance of this finding is still controversial. METHODS: In a group of 211 untreated patients with EH, we evaluated renal resistive index (RI) by US Doppler of interlobar arteries and early signs of target organ damage (TOD). Albuminuria was measured as the albumin to creatinine ratio (ACR) in three non-consecutive first morning urine samples. Left ventricular mass was evaluated by M-B mode echocardiography, and carotid wall thickness (IMT) by high resolution US scan. RESULTS: RI was positively correlated with age (r=0.25, P=0.003) and systolic blood pressure (SBP) (r=0.2, P=0.02) and with signs of early TOD, namely ACR (r=0.22, P=0.01) and IMT (r=0.17, P<0.05), and inversely correlated with renal volume (r=-0.22, P=0.01) and diastolic blood pressure (r=-0.23, P=0.006). Multiple linear regression analysis demonstrated that age, gender, ACR and SBP independently influence RI and together account for approximately 20% of its variations (F=8.153, P<0.0001). When clinical data were analysed according to the degree of RI, the patients in the top quartile were found to be older (P<0.05) and with higher SBP (P<0.05) as well as early signs of TOD, namely increased ACR (P<0.002) and IMT (P<0.005 by ANOVA), despite similar body mass index, uric acid, fasting blood glucose, lipid profile and duration of hypertension. Furthermore, patients with higher RI showed a significantly higher prevalence of microalbuminuria (13 vs 12 vs 3 vs 33% chi2=11.72, P=0.008) and left ventricular hypertrophy (40 vs 43 vs 32 vs 60%, chi2=9.25, P<0.05). CONCLUSIONS: Increased RI is associated with early signs of TOD in EH and could be a marker of intrarenal atherosclerosis.