Human dilated cardiomyopathy (DCM) manifests as a profound reduction in biventricular cardiac function that typically progresses to death or cardiac transplantation. There is no effective mechanism-based therapy currently available for DCM, in part because the transduction of mechanical load into dynamic changes in cardiac contractility (termed mechanotransduction) remains an incompletely understood process during both normal cardiac function and in disease states. Here we show that the mechanoreceptor protein integrin-linked kinase (ILK) mediates cardiomyocyte force transduction through regulation of the key calcium regulatory protein sarcoplasmic/endoplasmic reticulum Ca 2 þ ATPase isoform 2a (SERCA-2a) and phosphorylation of phospholamban (PLN) in the human heart. A non-oncogenic ILK mutation with a synthetic point mutation in the pleckstrin homology-like domain (ILK R211A ) is shown to enhance global cardiac function through SERCA-2a/PLN. Thus, ILK serves to link mechanoreception to the dynamic modulation of cardiac contractility through a previously undiscovered interaction with the functional SERCA-2a/PLN module that can be exploited to rescue impaired mechanotransduction in DCM.

In this report, we describe a case of a 61-year-old male patient who had the bacterium Dolosigranulum pigrum growing in a blood culture. It was susceptible to ampicillin, ceftriaxone, levofloxacin, and vancomycin but was intermediately resistant to erythromycin. The patient did not have a negative outcome as a consequence of this bacterium, which retrospectively could have been predicted based on the epidemiological data within the patient's profile.

Lung transplantation, the treatment of choice for end-stage lung disease, is associated with a high risk of graft failure and death. Anti-thymocyte globulin (ATG) and IL-2 inhibitors (Daclizumab or Basiliximab) are used for induction therapy in lung transplant recipients. The superiority of these drugs in reducing rejection and improving survival at one year is unclear. We conducted a systematic review and meta-analysis to compare the two approaches (ATG VS IL2 inhibitor) for induction therapy in lung transplant recipients. We also assessed secondary outcomes, including the incidence of significant infections, post-transplant lymphoproliferative disorders, and bronchiolitis obliterans syndrome. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane databases from inception through January-2020 using terms "anti-thymocyte globulin", "IL-2 inhibitor", "Daclizumab", and "Basiliximab". Studies comparing ATG and IL2 inhibitors (Daclizumab or Basiliximab) for induction therapy in lung transplant recipients were included in our analysis. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The random-effects model was used for all variables. Publication bias was assessed using Egger's test. RESULTS: Seven studies (four retrospective and three prospective) examining 791 patients, were included in our analysis. Five studies compared Daclizumab to ATG, and two compared Basiliximab to ATG. We found no significant differences between IL2 inhibitors and ATG regarding survival at one year, freedom from acute rejection at one year, or incidence of bronchiolitis obliterans syndrome with odds ratios of 0.89 (95% CI 0.19 to 4.28) (I 2 ¼89.94%), 1.13(95% CI 0.4 to 3.25) (I 2 ¼81.32%), and 0.76 (95% CI 0.26 to 2.26) (I 2 ¼65.72%) respectively. We also found no significant differences in the incidences of significant infections with an odds ratio of 0.45 (95% CI 0.12 to 1.71) (I 2 ¼58.88%) or CMV infections with an odds ratio of 1.41 (95% CI 0.21to 9.61) (I 2 ¼81.35%). No significant difference was found between the two groups regarding the incidence of Post-transplant lymphoproliferative disorder (PTLD) with an odds ratio of 0.35 (95% CI 0.09 to 1.24) (I 2 ¼0.00%). CONCLUSIONS: Our results suggest that ATG and IL2 inhibitors are similar regarding survival at one year, freedom from acute rejection at one year, and incidence of bronchiolitis obliterans syndrome. There was also no significant difference regarding incidences of significant infections, CMV infections, or post-transplant lymphoproliferative disorder between the two approaches. CLINICAL IMPLICATIONS: ATG and IL2 inhibitors (Daclizumab or Basiliximab) might have a comparable outcome when used for induction therapy in lung transplant patients.

Small cell variant of medullary thyroid carcinoma is an extremely rare histologic entity with a paucity of data. As such, there is a lack of literature and clinical experience regarding this disease. In this report, we examine a case of small cell variant of medullary thyroid carcinoma that presented with intractable nausea, vomiting and diarrhea. While these symptoms were essentially refractory to the standard symptomatic treatment, further laboratory analysis revealed dramatically elevated calcitonin levels and mildly raised thyroid-stimulating hormone levels. Interestingly, repletion of thyroid hormone and treatment with lanreotide resulted in an abatement of our patient's symptoms. This temporal clinical improvement highly suggests a potential role involving thyroid-stimulating hormone and calcitonin levels in the pathogenesis of this disease, and consequently suggests a role for thyroxine in treating the associated gastrointestinal symptoms.