Reducing therapeutic inertia in type 2 diabetes.

BACKGROUND: Therapeutic inertia describes a failure to establish appropriate treatment targets and escalate treatment to achieve those targets. This inertia can be measured, and evidence of this inertia is present in approximately one-third of diabetes management consultations. This inertia describes a failure in the system to produce change, rather than assigning fault to the physician or patient. OBJECTIVE: This article discusses the importance of reducing therapeutic inertia in type 2 diabetes and focusing on reducing overall cardiovascular risk. DISCUSSION: This article discusses approaches to reducing treatment inertia in type 2 diabetes (ie identify the problem, get permission, set goals, measure progress and alter treatment to reach those goals). The treat-to-target methodology, the STABLE (Smoking cessation, Target organ involvement, HbA1c, Blood pressure, Lipid profile, Energy balance) acronym and practical approaches are described.

Age-dependent heat shock hormesis to HSF-1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans.

The transcription factor HSF-1 (heat shock factor 1) acts as a master regulator of heat shock response in eukaryotic cells to maintain cellular proteostasis. The protein has a protective role in preventing cells from undergoing ageing, and neurodegeneration, and also mediates tumorigenesis. Thus, modulating HSF-1 activity in humans has a promising therapeutic potential for treating these pathologies. Loss of HSF-1 function is usually associated with impaired stress tolerance. Contrary to this conventional knowledge, we show here that inactivation of HSF-1 in the nematode Caenorhabditis elegans results in increased thermotolerance at young adult stages, whereas HSF-1 deficiency in animals passing early adult stages indeed leads to decreased thermotolerance, as compared to wild-type. Furthermore, a gene expression analysis supports that in young adults, distinct cellular stress response and immunity-related signaling pathways become induced upon HSF-1 deficiency. We also demonstrate that increased tolerance to proteotoxic stress in HSF-1-depleted young worms requires the activity of the unfolded protein response of the endoplasmic reticulum and the SKN-1/Nrf2-mediated oxidative stress response pathway, as well as an innate immunity-related pathway, suggesting a mutual compensatory interaction between HSF-1 and these conserved stress response systems. A similar compensatory molecular network is likely to also operate in higher animal taxa, raising the possibility of an unexpected outcome when HSF-1 activity is manipulated in humans.

Borderline phyllodes tumor arising in ectopic breast tissue in the axilla: Report of a rare case with brief review of literature.

Development of a neoplasm in an ectopic breast is uncommon, while the development of phyllodes tumor in an ectopic breast in the axilla is even rarer. We report a rare case of a 51-year-old female who presented with a complain of swelling and pain in the right axilla with no associated complaints in other organs. Magnetic resonance imaging suggested a possibility of metastatic lymphadenopathy. Complete excision of the right axillary mass was performed and sent for histopathological examination which was examined thoroughly and sections were given. On microscopic examination, stromal proliferation in a leaf-like pattern with mild stromal atypia and focal permeation of borders were seen, and a diagnosis of Ectopic borderline phyllodes tumor in axilla was made, which is extremely rare and needs to be differentiated from its close differentials like fibroadenoma and periductal stromal sarcoma.

Molecular Classification of Breast Carcinoma in a Tertiary Hospital of India: the Recent Trends.

Breast cancer is a heterogeneous disorder with various subcategories of different cellular compositions, molecular alterations, and clinical behaviour and is dependent on numerous factors like grade, size, and hormonal receptors which influence the overall prognosis and response to the treatment. This study was done to determine the frequency of estrogen receptor (ER), progesterone receptor (PR), and Her2 neu positivity in breast cancer patients, further classifying them into their molecular types (luminal A, B, Her2 neu, and triple-negative) and studying their association with histological subtypes, lymph node status, and other epidemiological parameters. This was a 5-year retrospective study done on 314 patients. All relevant clinical data including the age, sex, and lymph node status along with the histological type and grade of the tumour were recorded, and immunohistochemical evaluation of Her2 neu, ER, and PR receptors was done. The results showed that ER was the most predominant immunomarker, followed by PR, with an inverse relationship between ER, PR, and Her2 neu. Among the molecular subtypes, luminal B showed the maximum prevalence followed by triple-negative and Her2 neu subtype. The least frequency was shown by luminal A. Our study concluded that molecular subtyping of breast carcinoma plays an important role in determining the prognosis, recurrence, and treatment. Increased expression of luminal B subtype can be correlated due to the advancing age of the patients.

Functional diversification of heat shock factors.

Heat shock transcription factors (HSFs) are widely known as master regulators of the heat shock response. In invertebrates, a single heat shock factor, HSF1, is responsible for the maintenance of protein homeostasis. In vertebrates, seven members of the HSF family have been identified, namely HSF1, HSF2, HSF3, HSF4, HSF5, HSFX, and HSFY, of which HSF1 and HSF2 are clearly associated with heat shock response, while HSF4 is involved in development. Other members of the family have not yet been studied as extensively. Besides their role in cellular proteostasis, HSFs influence a plethora of biological processes such as aging, development, cell proliferation, and cell differentiation, and they are implicated in several pathologies such as neurodegeneration and cancer. This is achieved by regulating the expression of a great variety of genes including chaperones. Here, we review our current knowledge on the function of HSF family members and important aspects that made possible the functional diversification of HSFs.

Superficial Basal Cell Cancers Demonstrate Higher Rates of Mixed Histology on High-Risk Anatomical Sites.

BACKGROUND: The Mohs Appropriate Use Criteria (MAUC) have come into question recently regarding the most appropriate treatment for superficial basal cell carcinoma (sBCC). At the heart of this debate is the limited body of evidence describing tumor behavior of sBCC based on clinical factors relevant to the MAUC. OBJECTIVE: To determine whether sBCC is more likely to harbor aggressive subtypes in high-risk anatomical locations and in immunocompromised patients. MATERIALS AND METHODS: A single institution retrospective review produced 133 evaluable Mohs cases performed on sBCC over a 10-year period. All slides from the respective cases were reviewed for the presence of histologic patterns other than known sBCC. Cases were then grouped by both MAUC anatomical zone (H, M, and L) and patient immune status for statistical analysis. RESULTS: A significantly higher rate of mixed histology (MH) was observed when comparing Zone H with Zone L across all patients, healthy patients, and immunocompromised patients. The same was true when comparing Zone M with Zone L for all patients and healthy patients (immunocompromised did not reach significance). CONCLUSION: The authors' data very clearly demonstrate a higher rate of MH in sBCC of the head and neck which provides strong support to the current MAUC scoring.

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma.

Introduction: In September of 2018, the United States Federal Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is an intravenous human monoclonal antibody directed against programmed cell death-1 receptor (PD-1). Cemiplimab blocks T-cell inactivation and enhances the immune system's anti-tumor response. Areas Covered: We review CSCC and the studies leading to cemiplimab's approval, including common side effects and safety issues experienced during the clinical trials. Expert Opinion: Immunotherapy, specifically checkpoint inhibitors, represents an increasingly utilized class of medications that is proving to be an effective treatment option for those with certain cancers. Over time, immunotherapy is likely to be the standard of care for immune-sensitive tumors. There are many challenges that the field faces, including the identification of reliable biomarkers to better predict response, decreasing toxicity, and the potential treatment of organ transplant patients.

Review of systemic agents in the treatment of advanced cutaneous squamous cell carcinoma.

Advanced cutaneous squamous cell carcinoma (cSCC) accounts for only 5% of all cases of cSCC but up to 60% of disease related deaths. Historically, this disease has lacked effective treatment options due to a combination of poor response rate, poor response durability and significant treatment-associated morbidity. Autumn of 2018 marked the first time ever that an agent received US FDA approval for advanced cSCC and the future is looking much brighter for this previously neglected patient population. The purpose of this article is to review the various systemic treatment options for advanced cSCC moving from the past to the present, highlighting their relative merits and shortcomings, and to briefly speculate on future developments in the field of advanced cSCC.

Transoral robotic surgery (TORS) for excision of a retropharyngeal intramuscular lipoma.

OBJECTIVE: To describe the feasibility, effectiveness, and improved morbidity profile of transoral robotic surgery (TORS) for the excision of a retropharyngeal intramuscular lipoma. METHODS: Case report of a robot-assisted transoral resection of a retropharyngeal intramuscular lipoma. RESULTS: A 62-year-old woman presented with tongue pain and globus with dysphagia for six months. Transoral exam revealed a pharyngeal submucosal mass, and MRI demonstrated a prevertebral lipomatous lesion with protrusion into the airway. The patient elected for robot-assisted transoral surgical treatment. The patient tolerated the procedure well, experienced no complications, and was discharged on post-operative day one. At six months post-operatively, the patient was without dysphagia and was disease free on imaging. CONCLUSIONS: TORS is an effective, safe, feasible, and likely more efficient way to excise a retropharyngeal intramuscular lipoma or other retropharyngeal masses.

Velopharyngeal dysfunction in children with Prader-Willi syndrome after adenotonsillectomy.

INTRODUCTION: Prader-Willi syndrome (PWS) is a rare genetic disorder with an incidence rate of 1 in 10,000-30,000. Patients with PWS typically have symptoms related to hypotonia, obesity, and hypothalamic dysfunction. A high rate of obstructive sleep apnea (OSA) is found among this population of patients. Adenotonsillectomy has been advocated as a first line approach for treatment of OSA in patients with PWS. Velopharyngeal dysfunction (VPD) is a known complication of adenotonsillectomy. VPD can also be present in patients with global hypotonia, such as those with PWS. The objective of this study is to review the occurrence of VPD in patients with PWS after adenotonsillectomy for OSA. METHODS: A retrospective review was performed of all patients with PWS and OSA from a tertiary pediatric hospital between the years of 2002 and 2012. Pre- and post-operative sleep studies and sleep disordered breathing symptoms, post-operative VPD assessment by the speech-language pathologist (SLP), and VPD treatments were evaluated. RESULTS: Eleven patients (five males and six females), fitting the inclusion criteria, were identified. The age of the patient at the initial otolaryngologic evaluation ranged from 2 to 9 years. All patients underwent adenotonsillectomy for sleep disordered breathing. Four patients were diagnosed with post-operative hypernasality after assessment by a speech-language pathologist. The hypernasality ranged from mild to moderately severe. Of the four patients with hypernasality, two were found to have structural issues requiring surgery (pharyngeal flap). Both of the surgical patients experienced significant improvement in their VPD after surgery. The remaining two patients were found to have articulation error patterns that were considered more developmental in nature and both responded to speech therapy. All patients, except one, had improvement in their polysomnogram or sleep symptoms after adenotonsillectomy. However, three patients continue to require continuous positive airway pressure at night. CONCLUSION: Velopharyngeal dysfunction may occur after adenotonsillectomy in patients with Prader-Willi Syndrome. Families should be counseled of this risk and the potential need for operative intervention to correct it.