Pembrolizumab autoimmune related diabetes: Moving forward, keep learning.

Immune checkpoint inhibitors (and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab) initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts, including the adjuvant and neoadjuvant setting, with potentially curable patients and prolonged survival. The side effects related to these drugs include a wide spectrum of manifestations, with endocrinological adverse events being some of the most frequent. Pembrolizumab-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality, with a chronic impact on quality of life. The etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.

Anetoderma after disseminated Mpox.

Anetoderma or macular atrophy is a rare skin condition of unclear pathogenesis, often associated with autoimmune diseases and skin damage from various infections. Human immunodeficiency virus (HIV), syphilis, and poxviruses have been implicated in the development of anetoderma. A 37-year-old male patient with HIV and recent unprotected sexual encounters presented with more than 400 skin lesions, consistent with Mpox. Symptomatic treatment for Mpox resulted in acute symptom resolution. However, 8 months later he developed papular anetoderma lesions in areas previously affected by Mpox. Biopsy confirmed the loss of elastic fibers in the affected skin areas, leading to the diagnosis of Mpox-induced anetoderma. This report presents a unique case of anetoderma following Mpox in an HIV-positive patient.

Estimating the Prevalence of Cardiac Amyloidosis in Old Patients with Heart Failure-Barriers and Opportunities for Improvement: The PREVAMIC Study.

BACKGROUND: Cardiac amyloidosis (CA) could be a common cause of heart failure (HF). The objective of the study was to estimate the prevalence of CA in patients with HF. METHODS: Observational, prospective, and multicenter study involving 30 Spanish hospitals. A total of 453 patients ≥ 65 years with HF and an interventricular septum or posterior wall thickness > 12 mm were included. All patients underwent a 99mTc-DPD/PYP/HMDP scintigraphy and monoclonal bands were studied, following the current criteria for non-invasive diagnosis. In inconclusive cases, biopsies were performed. RESULTS: The vast majority of CA were diagnosed non-invasively. The prevalence was 20.1%. Most of the CA were transthyretin (ATTR-CM, 84.6%), with a minority of cardiac light-chain amyloidosis (AL-CM, 2.2%). The remaining (13.2%) was untyped. The prevalence was significantly higher in men (60.1% vs 39.9%, p = 0.019). Of the patients with CA, 26.5% had a left ventricular ejection fraction less than 50%. CONCLUSIONS: CA was the cause of HF in one out of five patients and should be screened in the elderly with HF and myocardial thickening, regardless of sex and LVEF. Few transthyretin-gene-sequencing studies were performed in older patients. In many patients, it was not possible to determine the amyloid subtype.

Lymph node metastasis in level IIb in oropharyngeal squamous cell carcinoma: a multicentric, longitudinal, retrospective analysis.

INTRODUCTION: Nowadays, 70% of patients in Europe and the USA are affected by a p16 + , potentially HPV driven oropharyngeal squamous cell carcinoma. However, despite the improved survival rate in this group, the quality-of-life remains low in cases which neck dissection took place. In this vein, in recent years, some surgeons have considered to avoid dissection of level IIB, proposing a supra-selective non-IIb neck dissection. MATERIALS AND METHODS: A retrospective, longitudinal, multicentric study was conducted, including patients with pathologically confirmed primary HPV + or HPV - OPSCC who went through surgical treatment for the primary lesion and neck dissection. RESULTS: 141 patients were included. Among them, 99 (70.2%) were male and 42 (29.8%) were female. The mean age was 62 ± 9 years (range 36-81). The most frequent anatomical location was the tonsil in 63 (44.7%) of patients. The most common approach was the classic transoral oropharyngectomy in 51 (36.2%) patients. Immunohistochemistry for p16 was positive in 62 (44%) patients. One-hundred and five (74.5%) patients received a unilateral ND, and a 36 (25.5%) a bilateral ND. Of those, a 12.8% (18/141) of patients were level IIb LN + . According to our results, level IIb ND should be considered in patients underwent therapeutic ND with positive LN metastasis in level IIa (OR = 9.83; 95% CI 3.463-27.917) or III (OR = 6.25; 95% CI 2.158-18.143), advanced (T3/T4) oropharyngeal primary tumors (OR = 3.38; 95% CI 1.366-8.405), and patients with ENE (OR = 6.56; 95% CI 2.182-19.770), regardless of p16 status. CONCLUSIONS: According to our results, level IIb ND should be considered in patients who underwent therapeutic ND with positive LN metastasis in level IIa or III, advanced oropharyngeal primary tumors, and patients with ENE, independently of p16 status. Prospective data are necessary to definitively ensure the safety of omitting ipsilateral or contralateral level IIb ND in cN - patients with early stage disease.

Transoral endoscopic ultrasonic surgery (TOUSS) in head & neck unknown primary carcinoma investigation.

Metastatic carcinoma of unknown primary (CUP) to cervical lymph nodes represents less than 5% of all head and neck malignancies. Recent publications support the use of transoral surgery during the diagnosis work-up, and transoral endoscopic ultrasonic surgery represent a recently described alternative technique in transoral surgery. A pilot study to assess the feasibility of trans-oral ultrasonic base of tongue (BOT) mucosectomy and bilateral tonsillectomy approach in CUP diagnosis work-up was conducted. Ten patients were included consecutively. In 2 cases (20%) the primary was found, in one case in the right tonsil, and another one in the left BOT. According to our results, the use of trans-oral ultrasonic surgery to perform the base of tongue mucosectomy and bilateral tonsillectomy in CUP patient's during the diagnosis work-up represents an effective option in patients with good anatomical exposure.

Gracilis free flap in head and neck reconstruction beyond facial palsy reanimation.

INTRODUCTION: The gracilis muscle free flap has gained popularity in head and neck reconstruction due to minimal donor-site morbidity, reliable vascular pedicle, strong muscular component, and possibility to perform nerve coaptation. However, almost all the existing evidence in the literature is related to its use for facial palsy reanimation. The aim of this study was therefore to review and provide a comprehensive summary of all the possible indications and outcomes of this versatile free flap in head neck reconstructive surgery. MATERIALS AND METHODS: A systematic review of the literature was conducted including articles from 1970 to 2019. All articles were examined and described. RESULTS: Twenty-seven papers published between 1994 and 2019 were identified for analysis. The evidence highlights the use of the gracilis muscle free flap for parotid, forehead and midface defects, oral tongue, oral sphincter, lower and upper lip, cheek, and oral commissure defects, among others, as the most common defects reconstructed. CONCLUSION: This flap represents an easy to harvest and versatile free flap with low donor-site morbidity and multiple proven uses in head & neck reconstruction. We therefore encourage reconstructive surgeons to include this flap in their armoury, either as a first or as a second-line option.

Correlation between MAMMI-PET findings and anatomopathological outcomes in breast cancer patients.

OBJECTIVE: Imaging tests are a key element in the preoperative diagnosis of patients with breast cancer. Whole-body PET-computed tomography (PET/CT) breast studies have a limited spatial resolution, although dedicated breast PET (dbPET) devices such as the Mammography with Molecular Imaging PET (MAMMI-PET), have an increased sensitivity to detect tumor foci, especially those smaller than 2 cm. The purpose of this study is to define the validity and reliability of this new device. METHODS: A prospective and analytical observational study was carried out in a sample of patients with histologically confirmed breast cancer who were treated at our hospital between January 2017 and November 2018. The anatomopathological study findings for the surgical pieces were used as gold standards and we calculated their concordance with the findings from the MAMMI-PET as well as the validity and reliability parameters for this test. RESULTS: Data from 32 patients and 44 lesions (36 malignant and 8 benign) were evaluated. The mean patient age was 51.50 ± 11.68 years. Twenty patients had received neoadjuvant chemotherapy (NACT). The technique concordance rate was weak ( K = 0.349, P = 0.001) and was 84.3% for benign lesions and 62.6% for malignant ones. The MAMMI-PET sensitivity was 75%, whereas its specificity was 57.1%; the positive predictive value was 81.8% and the negative predictive value was 47.1%, with an overall precision of 70%. The MAMMI-PET sensitivity was higher in patients who had not undergone NACT and was significantly higher in patients with luminal B breast cancer compared to the luminal A subtype. CONCLUSION: The MAMMI-PET device had acceptable sensitivity and a high positive predictive value for the preoperative evaluation of patients with breast cancer; it was especially useful for lesions whose diagnosis with other imaging tests had been doubtful.

Suicide after and during the COVID-19 pandemic in Mexico City

Objectives: Prior research has indicated that no increase in suicides occurred immediately following the declaration of the COVID-19 emergency in Mexico City. Here we examine longer-term overall suicide trends and trends according to basic demographic groups. Methods: We used interrupted time-series analysis to model trends in monthly suicides before COVID-19 (January 1, 2010 to March 31, 2020), comparing the expected number of suicides both overall and according to age and sex with the observed number of suicides for the remainder of 2020 (April 1, 2020 to December 31, 2020). Results: There was an overall increase in suicides during the first 9 months of the pandemic, with a rate ratio of 2.07 (1.86-2.31). The increase began in the early months of the pandemic and remained stable and high after June 2020. Men and women, younger people (< 45) and older people (≥ 45) were affected. The increase was especially high among older women (RR = 3.33; 2.04-5.15). Conclusions: The increase in suicides in Mexico City is worrying and highlights the need to strengthen economic development, mental health, and well-being programs. Suicides among older women should be closely monitored. There is an urgent need to expand primary health care services to include robust suicide prevention and treatment options.

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy.

BACKGROUND: Lately, major advances in crucial aspects of magnetic hyperthermia (MH) therapy have been made (nanoparticle synthesis, biosafety, etc.). However, there is one key point still lacking improvement: the magnetic field-frequency product (H × f = 4.85 × 108 Am-1s-1) proposed by Atkinson-Brezovich as a limit for MH therapies. Herein, we analyze both local and systemic physiological effects of overpassing this limit. METHODS: Different combinations of field frequency and intensity exceeding the Atkinson-Brezovich limit (591-920 kHz, and 10.3-18 kA/m) have been applied for 21 min to WAG/RijHsd male rats, randomly distributed to groups of 12 animals; half of them were sacrificed after 12 h, and the others 10 days later. Biochemical serum analyses were performed to assess the general, hepatic, renal and/or pancreatic function. RESULTS: MH raised liver temperature to 42.8 ± 0.4 °C. Although in five of the groups the exposure was relatively well tolerated, in the two of highest frequency (928 kHz) and intensity (18 kA/m), more than 50% of the animals died. A striking elevation in liver and systemic markers was observed after 12 h in the surviving animals, independently of the frequency and intensity used. Ten days later, liver markers were almost recovered in all of the animals. However, in those groups exposed to 591 kHz and 16 kA/m, and 700 kHz and 13.7 kA/m systemic markers remained altered. CONCLUSIONS: Exceeding the Atkinson-Brezovich limit up to 9.59 × 109 Am-1s-1 seems to be safe, though further research is needed to understand the impact of intensity and/or frequency on physiological conditions following MH.

Patterns of practice regarding surgical site infection prevention in head & neck surgery: An international survey.

INTRODUCTION: Head & neck surgery encompasses a variety of surgical approaches for benign and malignant conditions. Due to the complexity in treating patients with head and neck pathology, it is necessary to adhere to basic surgical principles to decrease complications. Among them, surgical site infection can be prevented using a surgery quality protocol including the correct use of antibiotics and optimization of nutritional status. MATERIALS AND METHODS: A survey was sent through the YO-IFOS and SEORL-CCC international mailing list. RESULTS: A total of 435 surgeons completed the survey. Of the respondents, 97.7% confirm that they scrub their hands before surgery, 40.9% respondents recommend nutritional support according to sign and symptoms, 60.9% use of antibiotic prophylaxis in clean surgery and just 9.2% use clindamycin in combination. CONCLUSION: This survey has broadened the scope regarding H&N surgical safety around the globe. Identifying innovative ways in which surgical care may be improved is mandatory.

Unplanned Hospital Readmission and Visit to the Emergency Room in the First Thirty Days after Head and Neck Surgery: A Prospective, Single-center Study

Abstract Introduction Head and neck surgery remains a complex field; the patients can suffer important functional or life-threating complications after treatment that need unplanned readmissions, increasing the cost related to the treatment. Objective To evaluate the incidence risk factors and causes associated with 30-day unplanned hospital readmission and visit to the emergency room (ER) after surgery for head and neck cancer. Methods Prospective, longitudinal, nonrandomized study. Results A total of 834 patients were included, 726 in the major surgery group and 108 in the minor surgery group. The 30-day readmission rate for all causes was of 7,9% for the patients treated by a major surgery and of 0% for the patients treated in the outpatient clinic for minor procedures, to a total readmission rate of 6,8%. The rate of visit to the emergency room for all causes in the first 30 days was of 14% for the patients treated by a major surgery and of 2,7% for the patients treated in the outpatient clinic. Conclusion Major surgery, the American Society of Anesthesiologists (ASA) status and type of wound are conditions related to unplanned readmission or visit to the ER in the first 30 day after discharge. The most commonly associated causes are infections or wound complications. An evidence-based risk stratification of the patients can be important to improve decision-making and resource utilization. An educational strategy can provide possible ways to improve the rate of readmission and reduce the amount of money expended by healthcare systems.

Unplanned Hospital Readmission and Visit to the Emergency Room in the First Thirty Days after Head and Neck Surgery: A Prospective, Single-center Study.

Introduction Head and neck surgery remains a complex field; the patients can suffer important functional or life-threating complications after treatment that need unplanned readmissions, increasing the cost related to the treatment. Objective To evaluate the incidence risk factors and causes associated with 30-day unplanned hospital readmission and visit to the emergency room (ER) after surgery for head and neck cancer. Methods Prospective, longitudinal, nonrandomized study. Results A total of 834 patients were included, 726 in the major surgery group and 108 in the minor surgery group. The 30-day readmission rate for all causes was of 7,9% for the patients treated by a major surgery and of 0% for the patients treated in the outpatient clinic for minor procedures, to a total readmission rate of 6,8%. The rate of visit to the emergency room for all causes in the first 30 days was of 14% for the patients treated by a major surgery and of 2,7% for the patients treated in the outpatient clinic. Conclusion Major surgery, the American Society of Anesthesiologists (ASA) status and type of wound are conditions related to unplanned readmission or visit to the ER in the first 30 day after discharge. The most commonly associated causes are infections or wound complications. An evidence-based risk stratification of the patients can be important to improve decision-making and resource utilization. An educational strategy can provide possible ways to improve the rate of readmission and reduce the amount of money expended by healthcare systems.

Programmed Death-Ligand 1 (PD-L1) as Immunotherapy Biomarker in Breast Cancer.

Breast cancer constitutes the most common malignant neoplasm in women around the world. Approximately 12% of patients are diagnosed with metastatic stage, and between 5 and 30% of early or locally advanced BC patients will relapse, making it an incurable disease. PD-L1 ligation is an immune inhibitory molecule of the activation of T cells, playing a relevant role in numerous types of malignant tumors, including BC. The objective of the present review is to analyze the role of PD-L1 as a biomarker in the different BC subtypes, adding clinical trials with immune checkpoint inhibitors and their applicable results. Diverse trials using immunotherapy with anti-PD-1/PD-L1 in BC, as well as prospective or retrospective cohort studies about PD-L1 in BC, were included. Despite divergent results in the reviewed studies, PD-L1 seems to be correlated with worse prognosis in the hormone receptor positive subtype. Immune checkpoints inhibitors targeting the PD-1/PD-L1 axis have achieved great response rates in TNBC patients, especially in combination with chemotherapy, making immunotherapy a new treatment option in this scenario. However, the utility of PD-L1 as a predictive biomarker in the rest of BC subtypes remains unclear. In addition, predictive differences have been found in response to immunotherapy depending on the stage of the tumor disease. Therefore, a better understanding of tumor microenvironment, as well as identifying new potential biomarkers or combined index scores, is necessary in order to make a better selection of the subgroups of BC patients who will derive benefit from immune checkpoint inhibitors.

Iron Oxide Nanorings and Nanotubes for Magnetic Hyperthermia: The Problem of Intraparticle Interactions.

Magnetic interactions can play an important role in the heating efficiency of magnetic nanoparticles. Although most of the time interparticle magnetic interactions are a dominant source, in specific cases such as multigranular nanostructures intraparticle interactions are also relevant and their effect is significant. In this work, we have prepared two different multigranular magnetic nanostructures of iron oxide, nanorings (NRs) and nanotubes (NTs), with a similar thickness but different lengths (55 nm for NRs and 470 nm for NTs). In this way, we find that the NTs present stronger intraparticle interactions than the NRs. Magnetometry and transverse susceptibility measurements show that the NTs possess a higher effective anisotropy and saturation magnetization. Despite this, the AC hysteresis loops obtained for the NRs (0-400 Oe, 300 kHz) are more squared, therefore giving rise to a higher heating efficiency (maximum specific absorption rate, SARmax = 110 W/g for the NRs and 80 W/g for the NTs at 400 Oe and 300 kHz). These results indicate that the weaker intraparticle interactions in the case of the NRs are in favor of magnetic hyperthermia in comparison with the NTs.

Biochemical and Metabolomic Changes after Electromagnetic Hyperthermia Exposure to Treat Colorectal Cancer Liver Implants in Rats.

BACKGROUND: Hyperthermia (HT) therapy still remains relatively unknown, in terms of both its biological and therapeutic effects. This work aims to analyze the effects of exposure to HT, such as that required in anti-tumor magnetic hyperthermia therapies, using metabolomic and serum parameters routinely analyzed in clinical practice. METHODS: WAG/RigHsd rats were assigned to the different experimental groups needed to emulate all of the procedures involved in the treatment of liver metastases by HT. Twelve hours or ten days after the electromagnetic HT (606 kHz and 14 kA/m during 21 min), blood samples were retrieved and liver samples were obtained. 1H-nuclear-magnetic-resonance spectroscopy (1H-NMR) was used to search for possible diagnostic biomarkers of HT effects on the rat liver tissue. All of the data obtained from the hydrophilic fraction of the tissues were analyzed and modeled using chemometric tools. RESULTS: Hepatic enzyme levels were significantly increased in animals that underwent hyperthermia after 12 h, but 10 d later they could not be detected anymore. The metabolomic profile (main metabolic differences were found in phosphatidylcholine, taurine, glucose, lactate and pyruvate, among others) also showed that the therapy significantly altered metabolism in the liver within 12 h (with two different patterns); however, those changes reverted to a control-profile pattern after 10 days. CONCLUSIONS: Magnetic hyperthermia could be considered as a safe therapy to treat liver metastases, since it does not induce irreversible physiological changes after application.

Functional Results of Transverse Extended Incision in Cervical Neck Dissection.

Introduction Multiple incisions have been described for the surgical approach of cervical neck nodes. All of these descriptions are associated with better or worse exposure of the surgical field as well as with different functional and aesthetic results, which are not always satisfactory. Objective Compare the transverse cervical incision with the classic incision in J or U. Methods This is a retrospective study of 47 patients who required cervical neck dissection between June 15, 2016 and June 15, 2017.A transversal incision was made in these surgeries, and their results were then compared with those of a group of 57 patients treated between January 1, 2010 and January 1, 2012, in whose cases an incision in J or U was made. Results Regarding the incision type, complications were present in 4 (8.5%) cases in the transversal incision group, and in 7 (12.2%) patients of the group of traditional incisions in J or U, without statistical differences ( p = 0.078). The only variables associated with complications of healing in the two groups was body mass index (BMI) < 18.5. The patients showed subjective satisfaction with the aesthetic result of the transverse incision, with an average of 7.51 vs 6.20 in the J or U incision. Conclusion The transverse incision represents a safe, aesthetic, and oncologically adequate option, associated with a lower cicatricial retraction rate, without significant complication rate and allowing adequate exposure of the surgical field, similar to the obtained with the classic incision in J or U.