Can cyclin-dependent kinase 4/6 inhibitors convert inoperable breast cancer relapse to operability? A case report

BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures.The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced p CR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a p CR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified asendocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable.     

Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study

Background and aimsCholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM.Methods and results57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA.A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP.ConclusionExogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.     

Twelve-month prospective,multinational, observational study of factors associated with recovery from mania in bipolar disorder in patients treated with atypical antipsychotics

Abstract

Objectives. Atypical antipsychotic agents constitute one therapeutic approach for bipolar disorder. Since disease course and outcome are variable, further studies are needed to complement limited data supportive of clinical decisions at treatment initiation. Methods. This 12-month, prospective, observational study investigated factors associated with symptomatic remission (total YMRS score ≤12) and full clinical recovery (sustained reduction in CGI-BP-S overall score) in bipolar disorder during treatment with atypical antipsychotics (predominantly olanzapine, risperidone and quetiapine; alone or in combination with a psychotropic such as lithium or valproate) in actual clinical practice. Results. Amongst 872 enrolled and eligible patients, rates of symptomatic remission and full clinical recovery at 12 months were 93.0 and 78.5%, respectively. Of the baseline factors significantly (P≤0.05) associated with symptomatic remission, the following categories were positively associated with a higher chance of symptomatic remission: Caucasian ethnicity; higher CGI-BP-S scores; family-dependent living; a previous manic episode; 1, 2 or ≥5 social activities; no work impairment; and being neither satisfied nor dissatisfied with life. Outpatient treatment and historically longer periods of mania were significantly positively associated with full clinical recovery. Conclusions. While clinical status may also be associated with longer-term remission and recovery, factors relating to social functioning and quality of life are easily assessed and potentially modifiable. Such knowledge may aid physicians' clinical decisions regarding patients with bipolar mania treated with atypical antipsychotics.     

Complete remission of leiomyosarcoma with lung and brain metastasis by chemoradiotherapy after surgery

Nowadays, leiomyosarcoma is stil dif icult to early diagnosis, has no standard treatment to fol ow, and the thera-peutic value of surgery, chemotherapy and radiotherapy haven’t been evaluated ef ective...     

TMJ Vibrations in Asymptomatic Patients Using Old and New Complete Dentures

Purpose: The aim of this study was to assess the presence of temporomandibular joint (TMJ) noises in subjects with severe bone resorption, who have worn the same complete dentures for over 10 years, and 5 months after treatment with increments of acrylic resin on the occlusal surface after having new dentures in place. Methods: After applying the research diagnostic criteria (RDC)/temporomandibular disorder (TMD) questionnaire, 20 asymptomatic subjects were assessed before and 5 months after the new dentures were put in place. Joint vibrations were assessed by the Sono Pak program by selecting the vibrations that occurred during the opening and closing cycle. Results: The means of the results revealed a nonnormal distribution and were submitted to Kruskal‐Wallis statistical analysis (p < 0.05). The vibration means were of low intensity (≤9.96 Hz). After rehabilitation, there was a reduction in the vibrations (≤5.2 Hz) statistically significant only at the end of mouth opening with the old dentures when compared with the other cycles. Conclusion: The intensity and number of occurrences of joint vibrations were reduced after 5 months of wearing new dentures.     

Long-Term Outcomes of Complete Revascularization With Percutaneous Coronary Intervention in Acute Coronary Syndromes

ObjectivesThe aim of this study was to evaluate the long-term outcomes of patients with acute coronary syndromes (ACS) with multivessel disease undergoing percutaneous coronary intervention (PCI).BackgroundControversy exists regarding the benefit of multivessel PCI across the spectrum of ACS.MethodsA total of 9,094 patients with ACS and multivessel disease (≥70% stenosis in 2 or more major epicardial vessels) undergoing PCI from the Alberta COAPT (Contemporary Acute Coronary Syndrome Patients Invasive Treatment Strategies) registry (April 1, 2007, to March 31, 2013) were reviewed. Comparisons were made between patients who underwent complete revascularization and those with incomplete revascularization. Complete revascularization was defined as multivessel PCI with a residual angiographic jeopardy score ≤10%. Associations between revascularization status and all-cause death or new myocardial infarction (primary composite endpoint) and all-cause death, new myocardial infarction, or repeat revascularization (secondary composite endpoint) were evaluated.ResultsOf the study cohort, 66.0% underwent complete revascularization. Compared with incomplete revascularization, the primary composite endpoint occurred less frequently with complete revascularization (event rate within 5 years 15.4% vs. 22.2%; inverse probability-weighted hazard ratio [IPW-HR]: 0.78; 95% confidence interval [CI]: 0.73 to 0.84; p < 0.0001). The secondary composite endpoint was less likely to occur with complete revascularization (event rate within 5 years 23.3% vs. 37.5%; IPW-HR: 0.61; 95% CI: 0.58 to 0.65; p < 0.0001). Complete revascularization was associated with a reduction in all-cause death (IPW-HR: 0.79; 95% CI: 0.73 to 0.86; p = 0.0004), new myocardial infarction (IPW-HR: 0.76; 95% CI: 0.69 to 0.84; p < 0.0001), and repeat revascularization (IPW-HR: 0.53; 95% CI: 0.49 to 0.57; p < 0.0001).ConclusionsResults from this large contemporary registry of patients with ACS and PCI for multivessel disease suggest that complete revascularization occurs commonly and is associated with improved clinical outcomes (including survival) within 5 years.     

Reasons for drinking less and their relationship to sustained remission from problem drinking

AIMS: To compare representative general population and treated samples on their reasons for drinking less and whether particular reasons were related to sustained remission from problem drinking for either group. PARTICIPANTS AND DESIGN: A total of 659 problem drinking adults in a Northern California county identified through a probability survey in the general population (n = 239) and a survey of consecutive admissions to public and private alcohol and drug programs (n = 420), who reported drinking less at the one-year follow-up and provided reasons for reducing their drinking, were assessed 1-, 3-, and 5-years post-baseline regarding their problem drinking status. MEASUREMENTS: Logistic regression models were used to predict sustained remission from problem drinking. RESULTS: While the treated sample endorsed a majority of reasons in significantly higher proportions than the general population sample, the same three reasons were significant for both groups in predicting sustained remission from problem drinking: hitting rock bottom, experiencing a traumatic event and undergoing a spiritual awakening. Interventions by medical personnel and family members were either non-significant predictors or significantly negatively related to sustained improvement for both general population and treated problem drinkers. CONCLUSIONS: General population and treatment samples have similar reasons for cutting down as they relate to sustained remission from problem drinking.