RESUMEN

BACKGROUND: Warfare represents a significant source of stress in contemporary times, with enduring implications beyond the immediate casualties, fostering a pervasive atmosphere of danger and anxiety within affected populations. The Israel-Hamas war, marked by ongoing armed incursions and missile attacks, stands as a recent example of such turmoil, inflicting widespread trauma and disruption. METHODS: This study, conducted among students at the Ashkelon Academic College in southern Israel, aimed to investigate the stress levels and associated factors amidst the ongoing conflict. Utilizing a cross-sectional survey design, data were collected from 625 participants between January and February 2024, approximately four months after the commencement of the initial attack. The survey encompassed demographic information, perceived stress levels, sleep quality, and social media usage. RESULTS: The findings revealed moderate to high stress levels among participants, with significant differences observed based on gender, parental status, and residency in conflict zones. Moreover, poorer sleep quality was reported among students residing in conflict-affected areas. Regression analysis identified several predictors of elevated stress, including gender, parental status, sleep quality, residency in conflict zones, and social media usage. CONCLUSIONS: These findings underscore the profound impact of ongoing conflict on college students' mental well-being, highlighting the need for tailored interventions and support services within higher education institutions. The limitations include the study's focus on a specific college population and the timing of the data collection relative to the onset of the war. Nonetheless, this research contributes valuable insights concerning the stress dynamics within the unique context faced by Israeli students amidst ongoing warfare.

RESUMEN

BACKGROUND: The report of the Lancet Commission on medicine, Nazism, and the Holocaust, released in November 2023, calls for this history to be required for all health professions education, to foster morally courageous health professionals who speak up when necessary. MAIN BODY: The report was released a month after Hamas' October 7 invasion of Israel, with the accompanying massacre of over 1200 people, taking of civilian hostages, and gender-based violence. These acts constitute crimes against humanity including genocide. Post-October 7, war in Gaza resulted, with a legitimate objective of Israel defending itself within international law. The authors discuss an accompanying Statement to the report condemning Hamas crimes and denouncing the perpetrators' use of their own civilians as human shields, including in healthcare facilities, and with the Hamas attack unleashing immense and ongoing suffering in Israel and beyond. With some exceptions, the medical literature shows a marked absence of condemnation of Hamas atrocities and includes unsubstantiated criticisms of Israel's military. A significant surge in global antisemitism including on university campuses since October 7, 2023, has occurred; and health professionals, according to the Commission, have a special responsibility to fight antisemitism and discrimination of all kinds. In this context, the authors discuss the controversy and criticism regarding diversity, equity, and inclusion education programs ("DEI") including such programs failing to protect Jews on campuses, especially as the U.S. President Biden's "The U.S. National Strategy to Counter Antisemitism," released in May 2023, calls for the inclusion of issues of antisemitism and religious discrimination within all DEI education programs. The authors support an evidence-based approach to the Hamas massacre, its aftermath and its relevance to health professionals both within medicine and their global citizenship, including refuting the international community accusations and anti-Israel libel. CONCLUSIONS: The report of the Lancet Commission on medicine, Nazism, and the Holocaust has striking relevance to the Hamas massacre of October 7, 2023 and its aftermath. This is further conveyed in an accompanying Statement, that describes the report's implications for contemporary medicine, including: 1) provision of skills required to detect and prevent crimes against humanity and genocide; (2) care for victims of atrocities; (3) upholding the healing ethos central to the practice of medicine; and (4) fostering history-informed morally courageous health professionals who speak up when necessary.

Asunto(s)

RESUMEN

Background: The ideal combination regimen for Helicobacter pylori (HP) eradication has not yet been determined and the success rate of HP eradication has been extensively reduced worldwide due to increasing antibiotic resistance. So this multinational multi-center randomized controlled trial was designed to evaluate the efficacy of tetracycline +levofloxacin for HP eradication. Methods: During a 6-month period, all of the cases with HP infection in eight referral tertiary centers of three countries were included and randomly allocated to receive either tetracycline + levofloxacin or clarithromycin plus amoxicillin quadruple regimen for two weeks. For all of the participants, pantoprazole was continued for 4 more weeks and after one to two weeks of off-therapy, they underwent urea breath test C13 to prove eradication. Results: Overall 788 patients were included (358 male (45.4%), average age 44.2 years). They were diagnosed as having non-ulcer dyspepsia (516 cases, 65.5%), peptic ulcer disease (PUD) (234 cases, 29.69%), and intestinal metaplasia (38 cases, 4.8%). Racially 63.1% were Caucasian, 14.5% Arab, 15.6% African, and 6.1% Asian. The participants were randomly allocated to groups A and B to receive either tetracycline + levofloxacin or clarithromycin. Among groups A and B in intention to treat (ITT) and per protocol (PP) analysis, 75.2% & 82.1% (285 cases) and 67.5% & 70.1% (276 cases) of participants achieved eradication, respectively (P = 0.0001). The complete compliance rate in groups A and B were 84.4% and 83.6%, respectively. During the study, 33.5% of the participants in group A (127 cases) reported side effects while the complication rate among group B was 27.9% (114 cases, P = 0.041). The most common complaints among groups A and B were nausea and vomiting (12.6% & 9.3%) and abdominal pain (4.48% & 2.68%), respectively. The rate of severe complications that caused discontinuation of medication in groups A and B were 2.1% and 1.46%, respectively (P = 679). In subgroup analysis, the eradication rates of tetracycline+levofloxacin among patients with non-ulcer dyspepsia, PUD, and intestinal metaplasia were 79.4%, 88.1%, and 73.9%, respectively. These figures in group B (clarithromycin base) were 71.3%, 67.6%, and 61.5% respectively (P = 0.0001, 0.0001, and 0.043). Conclusion: Overall, the combination of tetracycline+levofloxacin is more efficient for HP eradication in comparison with clarithromycin+amoxicillin despite more complication rate. In areas with a high rate of resistance to clarithromycin, this therapeutic regimen could be an ideal choice for HP eradication, especially among those who were diagnosed with PUD.

RESUMEN

Objective: This study aims to evaluate the impact of the Pink October Campaign on the increase in mammographic screening in Brazil. Study design: Ecological observational study, based on retrospective data. Methods: Brazilian national screening database (DATASUS/SISMAMA/Information System on Breast Cancer) was used as a data source and is publicly available for download and analysis. We report screening numbers and outcome rates from January 2017 to December 2021 comparing statistically (ANOVA test, post-Tukey test), age groups, regions of Brazil, and the four quarters of the year. Results: During the study period, the average number of exams performed monthly over the five years was 137,400.117. An increase in the number of mammograms performed in October was identified, as well as in the two following months, respectively 33%, 39%, and 22%, with statistical significance (p = 0.000) in relation to the three quarters of the year. In addition, in the other months, we found values below the monthly average. Statistical difference was not found in the increase in mammograms considering age groups (p = 0.5) and different regions of the country (p = 0.6). Conclusions: This study showed an increase in mammographic screening in the three months following the Pink October Campaign, so we should intensify similar actions throughout the year and not just in October.

RESUMEN

On October 30th, 2020, a magnitude 7.0 earthquake offshore off the northern coast of Samos, Greece, generated a tsunami that impacted the nearshore Greek islands and the Aegean coastline of Turkey. Here, we describe detailed results from several post-event field surveys, and report first wave arrival timing and polarity information as well as tsunami height/runup measurements, from five islands. In Chios, wave runup reached 1.38 m, in Samos ~ 3 m, in Fourni 1.57 m, in Thimena 1.46 m, and in Ikaria 1.18 m. This event marks two milestones. One, the General Secretariat for Civil Protection of Greece, disseminated a message through Greece's 1-1-2 Emergency Communications Service to all cell phones in the eastern Aegean geographical region, warning recipients to stay away from coastal areas. According to eyewitnesses, the message was received ~ 3-5 min prior to the second and largest flood in Vathi, as the first flood had not sufficiently alarmed the local authorities to evacuate residents. Two, we were able to infer complete tsunami hydrographs from measurements for the first two floods in Vathi, which suggests that the water level rose to about one meter overland flow depth in one minute.

RESUMEN

Objetivo: Descrever a experiência de um estágio acadêmico vivenciado por universitários da área da saúde em um município do Baixo Solimões. Síntese dos dados:Trata-se do relato descritivo de um estágio acadêmico extramuro realizado em Manacapuru, Amazonas, ocorrido no período de outubro de 2019 a fevereiro de 2020. A realização da atividade teve a participação de acadêmicos de Medicina, Enfermagem e Odontologia e contou com a aplicação de práticas em saúde direcionadas à atuação individual e coletiva. Tendo como público-alvo os pacientes atendidos por uma Unidade Básica de Saúde (UBS), os universitários auxiliaram na realização de atendimentos eletivos em suas respectivas áreas de atuação e conduziram atividades de educação em saúde como rodas de conversa, gincanas educativas, palestras interativas e educação continuada à equipe da UBS. Conclusão: As práticas e ações em saúde realizadas no período do estágio extramuro proporcionaram uma integração interdisciplinar satisfatória entre os acadêmicos, possibilitando aos mesmos uma vivência apropriada na atenção básica do Sistema Único de Saúde (SUS).

Objective: To describe the experience of an academic internship completed by university students in the health field in a municipality in Baixo Solimões. Data synthesis: This is a descriptive report of an extramural academic internship carried out in Manacapuru, Amazonas, from October 2019 to February 2020. The activity was carried out with the participation of medical, nursing and dentistry students and included the application of health practices aimed at individual and collective action. Having as a target audience the patients assisted by a Primary Health Care (PHC) center, the university students helped in carrying out elective care in their respective fields and conducted health education activities such as conversation circles, educational scavenger hunts, interactive lectures and continuing education for the PHC center team. Conclusion: The health practices and actions carried out during the extramural internship enabled a satisfactory interdisciplinary integration among the students and allowed them to have an appropriate experience in primary care in the Unified Health System (Sistema Único de Saúde ­ SUS).

Objetivo: Describir la experiencia de una pasantía académica vivida por universitarios del área de la salud en un municipio del Baixo Solimões. Síntesis de los datos: Se refiere al informe descriptivo de una pasantía académica extramuros realizado en Manacapuru, Amazonas, ocurrido entre octubre de 2019 y febrero de 2020. La realización de la actividad tuvo la participación de académicos de medicina, enfermería y odontología y contó con la aplicación de prácticas en salud direccionadas a la actuación individual y colectiva. Teniendo como público meta los pacientes atendidos por una Unidad Básica de Salud (UBS), los universitarios ayudaron en la realización de atendimientos electivos en sus respectivas áreas de actuación y condujeron actividades de educación y en salud como charlas, juegos educativos, conferencias interactivas y educación continuada para el equipo de la UBS. Conclusión: Las prácticas y acciones en salud realizadas en el período de la pasantía extramuros proporcionaron una integración interdisciplinar satisfactoria entre los académicos, posibilitando a los mismos una experiencia apropiada en la atención básica del Sistema Único de Salud (SUS).

RESUMEN

In 2020, the rules governing the practice of abortion in Poland were narrowed and became some of the strictest in Europe. These new rules were the result of the Constitutional Court's oral announcement of its judgment in case K 1/20, making abortion for embryo-pathological reasons illegal. Thus, terminations of pregnancy in cases where prenatal tests and other medical findings indicated a high risk of a severe and irreversible damage to the foetus, or an incurable life-threatening ailment of the foetus, which in 2018 accounted for approximately 98% of all abortions in Poland, were declared illegal. In the Constitutional Court's written opinion, however, the court included a statement that may constitute a basis for broader interpretation, namely, that reasons of an embryo-pathological nature, insofar as they pose a threat to the life or health of the pregnant woman, may constitute a basis for legal termination of a pregnancy on the grounds of "the mother's well-being." But it is not clear in the Court's opinion how many doctors (and of what specialties) should make the relevant evaluation that would constitute sufficient legal justification for a decision to perform a legal abortion, thereby mitigating the risk of facing legal liability for terminating a pregnancy. For these reasons, doctors are likely to bear the burden that should have been placed on the legislators, who are, after all, obliged to consistently and exhaustively consider all the factual situations that are bound to happen in medical practice. Such factual situations should be addressed by thoughtful legislation instead of subjecting physicians to potentially unorthodox or free interpretation of laws falling short of meeting the actual needs of their patients.

Asunto(s)

RESUMEN

PURPOSE: People with aphasia post-stroke are at risk for depression and social isolation. Peer-befriending from someone with similar experiences may promote wellbeing and provide support. This paper explored the views of people with aphasia and their significant others about peer-befriending. MATERIALS AND METHODS: We conducted a qualitative study within a feasibility trial (SUPERB) on peer-befriending for people with post-stroke aphasia and low levels of distress. Of the 28 participants randomised to the intervention, semi-structured in-depth interviews were conducted with 10 purposively selected people with aphasia (at both 4- and 10-months post-randomisation) and five of their significant others (at 4-months). Interviews were analysed using Framework Analysis. RESULTS: Participants and their significant others were positive about peer-befriending and identified factors which influenced their experience: the befrienders' personal experience of stroke and aphasia, their character traits and the resulting rapport these created, the conversation topics they discussed and settings they met in, and the logistics of befriending, including planning visits and negotiating their end. Interviewees also made evaluative comments about the befriending scheme. CONCLUSION: Peer-befriending was an acceptable intervention. Benefits for emotional wellbeing and companionship were reported. The shared experience in the befriending relationship was highly valued.Implications for RehabilitationThe lived experience of stroke and aphasia of befrienders was highly valued by people with aphasia receiving peer-befriending.Training, regular supervision, and support for befrienders with practicalities such as organising visits ensured the befriending scheme was perceived as straightforward and acceptable by befriendees.Those receiving peer-befriending would recommend it to others; they found it beneficial, especially in terms of emotional wellbeing and companionship.

Asunto(s)

RESUMEN

PURPOSE: The aim of this study is to determine the financial impact of clinical complications and outcomes after minimally invasive Ivor Lewis esophagectomy (MILE) at a safety-net hospital. METHODS: This was a single-center retrospective analysis of consecutive patients undergoing MILE from 2013 to 2018. Postoperative complications were classified by Clavien-Dindo grade and associated total and direct recovered costs were assessed. Direct cost and LOS index were defined as the ratio of observed to expected values (>1 denotes above nationwide expectations). Annual outcomes were based on Medicare fiscal years. RESULTS: One hundred twenty-four patients (99 males, mean age 65.7 ± 9.3) were surgically treated for esophageal malignancy (n = 118) and benign disease (n = 6) by MILE between 2014 and 2018. Mean ICU LOS (5.8 ± 6.6 versus 4.3 ± 6.3 days) and LOS index (1.16 versus 0.76) improved from 2014 to 2018. Both direct cost index (1.03 versus 0.99) and indirect costs (43.4% versus 41.4%) decreased over time. However, direct costs recovered (213.6 to 159.0%) and total costs recovered (119.1 to 92.5%) declined during this period. Clinical complications grade was not associated with total costs recovered (p = 0.69). Extent of recovered expenditure was significantly higher from commercial/private payers as compared to government-sponsored payers (p < 0.05). CONCLUSION: Improvement in clinical outcomes and efficiency of care are not reflected by annual recovered expenditure. Furthermore, clinical complications do not correlate with the ability to recover hospital spending. Financial recovery was primary payer dependent. Enhanced collaboration with hospital administration may be needed in an effort to maximize financial fidelity in the presence of good quality of care after highly complex procedures.

Asunto(s)

RESUMEN

BACKGROUND: Tissue culture and rapid propagation technology is an important way to solve the difficulties of plant propagation. This experiment aims to explore the appropriate conditions at each stage of the red maple's tissue culture process and to obtain plantlets, thus providing a theoretical basis for the establishment of the red maple's tissue culture system. RESULTS: The results showed that the stem segment is the most suitable explant for inducing embryogenic callus. The MS (Murashige&Skoog) + 0.8 mg/L TDZ (Thidiazuron) + 1.0 mg/L 6-BA (6-Benzylaminopurine) + 0.5 mg/L IAA(Indole-3-acetic acid) + 35 g/L sucrose+ 7.5 g/L semi-fixed medium was the best for callus formation. When selecting type VI callus as embryonic callus induction material, MS + 0.6 mg/L TDZ + 0.5 mg/L 6-BA + 2.0 mg/L IAA + 35 g/L sucrose+ 7.5 g/L semi-fixed medium can get embryonic callus. The optimal medium for adventitious bud induction is MS + 1.0 mg/L TDZ + 3.0 mg/L 6-BA+ 0.2 mg/L NAA (1-Naphthaleneacetic acid) + 1.2 mg/L IAA + 35 g/L sucrose+ 7.5 g/L semi-fixed medium. The induction rate of adventitious roots in MS + 0.6 mg/L TDZ + 1.0 mg/L 6-BA+ 3 mg/L NAA + 35 g/L sucrose+ 7.5 g/L semi-fixed medium was the highest, reaching 76%. CONCLUSIONS: In the course of our research, we found that PGRs play an important role in the callus induction stage, and the effect of TDZ is particularly obvious; The callus cells grow and proliferate according to the "S" growth curve, and can be sub-cultured when the highest growth point is reached to maintain the rapid proliferation of the callus cells and to avoid inactivation of callus caused by tight niche.

Asunto(s)

RESUMEN

Resumen La psicología en tanto práctica profesional y de investigación científica no puede ni debe permanecer aislada de los contextos en los que se desarrolla. Frente a los profundos sentimientos de malestar expresados por el pueblo chileno en movilizaciones sociales desde el 18 de octubre de 2019, que responden directamente a la implementación de un modelo neoliberal desprovisto de justicia social, como psicólogas y psicólogos nos sentimos llamados a levantar los requerimientos mínimos que consideramos que nuestra disciplina debe asumir. Bajo este marco, se presenta un Manifiesto que contempla 22 puntos, construido de manera colaborativa por 13 psicólogas y psicólogos de diversas instituciones que, en una labor colectiva, lo proponen como agenda de trabajo para los próximos meses. Sabiendo que este listado no es definitivo ni exhaustivo, lo ofrecemos a la comunidad como un punto de partida para la deliberación, discusión y debate dentro de Universidades, centros de investigación, sociedades científicas y profesionales y al aparato estatal, de manera de fortalecer el rol de la psicología en la problematización y reducción las inequidades e injusticias, así como en el fomento del bienestar psicosocial.

Abstract Psychology as a professional and scientific practice should and must not remain isolated from the contexts in which it develops. Considering the deep feelings of discomfort expressed by the Chilean people during social mobilizations since October 18th, 2019, in response to the implementation for decades of a neoliberal model devoid of social justice, as psychologists we feel summoned to raise the minimum requirements we think our discipline must assume about that matter. Under these assumptions, a Manifesto is presented. It includes 22 items, which have been elaborated by 13 psychologists from several institutions that, in a collective effort, propose them as an agenda to work on in the next months. Knowing that this list is not definitive or exhaustive, we offer it to the community as a point of departure for deliberation, discussion and debate within universities, research centers, scientific and professional societies, and the state apparatus, in order to strengthen the role of psychology in the problematization and reduction of inequities and injustices, as well as in promoting psychosocial well-being.

Asunto(s)

RESUMEN

SUMMARY: Silent corticotroph adenoma (SCA) is an unusual type of nonfunctioning pituitary adenoma (NFA) that is silent both clinically and biochemically and can only be recognized by positive immunostaining for ACTH. Under rare circumstances, it can transform into hormonally active disease presenting with severe Cushing syndrome. It might often produce diagnostic dilemma with difficult management issue if not thoroughly investigated and subtyped accordingly following surgery. Here, we present a 21-year-old male who initially underwent pituitary adenomectomy for presumed NFA with compressive symptoms. However, he developed recurrent and invasive macroadenoma with severe clinical as well as biochemical hypercortisolism during post-surgical follow-up. Repeat pituitary surgery was carried out urgently as there was significant optic chiasmal compression. Immunohistochemical analysis of the tumor tissue obtained on repeat surgery proved it to be an aggressive corticotroph adenoma. Though not cured, he showed marked clinical and biochemical improvement in the immediate postoperative period. Anticipating recurrence from the residual tumor, we referred him for cyber knife radio surgery. LEARNING POINTS: Pituitary NFA commonly present with compressive symptoms such as headache and blurred vision. Post-surgical development of Cushing syndrome in such a case could be either drug induced or endogenous. In the presence of recurrent pituitary tumor, ACTH-dependent Cushing syndrome indicates CD. Rarely a SCA presenting initially as NFA can transform into an active corticotroph adenoma. Immunohistochemical marker for ACTH in the resected tumor confirms the diagnosis.

RESUMEN

SUMMARY: ACTH-dependent hypercortisolism is caused by an ectopic ACTH syndrome (EAS) in 20% of cases. We report a rare cause of EAS in a 41-year-old woman, presenting with clinical features of Cushing's syndrome which developed over several months. Biochemical tests revealed hypokalemic metabolic alkalosis and high morning cortisol and ACTH levels. Further testing, including 24-hour urine analysis, late-night saliva and low-dose dexamethasone suppression test, confirmed hypercortisolism. An MRI of the pituitary gland was normal. Inferior petrosal sinus sampling (IPSS) revealed inconsistent results, with a raised basal gradient but no rise after CRH stimulation. Additional PET-CT showed intense metabolic activity in the left nasal vault. Biopsy of this lesion revealed an unsuspected cause of Cushing's syndrome: an olfactory neuroblastoma (ONB) with positive immunostaining for ACTH. Our patient underwent transnasal resection of the tumour mass, followed by adjuvant radiotherapy. Normalisation of cortisol and ACTH levels was seen immediately after surgery. Hydrocortisone substitution was started to prevent withdrawal symptoms. As the hypothalamic-pituitary-axis slowly recovered, daily hydrocortisone doses were tapered and stopped 4 months after surgery. Clinical Cushing's stigmata improved gradually. LEARNING POINTS: Ectopic ACTH syndrome can originate from tumours outside the thoracoabdominal region, like the sinonasal cavity. The diagnostic accuracy of IPSS is not 100%: both false positives and false negatives may occur and might be due to a sinonasal tumour with ectopic ACTH secretion. Olfactory neuroblastoma (syn. esthesioneuroblastoma), named because of its sensory (olfactory) and neuroectodermal origin in the upper nasal cavity, is a rare malignant neoplasm. It should not be confused with neuroblastoma, a tumour of the sympathetic nervous system typically occurring in children. If one criticises MRI of the pituitary gland because of ACTH-dependent hypercortisolism, one should take a close look at the sinonasal field as well.

RESUMEN

SUMMARY: Although pheochromocytoma classically presents with headaches, palpitations and paroxysmal hypertension, atypical presentations such as cardiomyopathy, stroke and subarachnoid haemorrhage have been infrequently documented. We present in this case report, an uncommon presentation of pheochromocytoma with myocardial infarction with normal coronary arteries (MINOCA). A 79-year-old woman presented with central crushing chest pain radiating to left arm associated with headache, palpitations, sweating and difficulty in breathing. For 2 years, she experienced brief episodes of headache, tinnitus, dizziness, palpitations, and sweating that spontaneously resolved. Clinical examination was unremarkable except for high blood pressure (210/105 mmHg). Her electrocardiogram showed T wave inversions from V1 to V6 and elevated troponins (774 ng/L at baseline and 932 ng/L 3 h from baseline (normal <16 ng/L) in keeping with a diagnosis of non-ST elevated myocardial infarction. Coronary angiography showed normal coronary arteries. Patient was hence treated as myocardial infarction with normal coronaries (MINOCA). Despite appropriate treatment for MINOCA, she continued to experience episodic headaches, palpitations, dizziness and erratic blood pressures (particularly severe hypertension shortly after beta-blocker administration). Further investigations revealed raised urine noradrenaline of 4724 nmol/24 h (<554 nmol/24 h) and urine adrenaline of 92863 nmol/24 h (<77 nmol/24 h). Computerised tomography demonstrated a well-defined rounded mass in right adrenal gland morphological of pheochromocytoma. She underwent laparoscopic right adrenalectomy with histology confirming pheochromocytoma. This case highlights the importance of thorough investigation for the underlying cause for MINOCA. In patients with unexplained erratic blood pressure control, pheochromocytoma should be considered as a differential diagnosis. LEARNING POINTS: Pheochromocytoma is rare tumour that often presents with non-specific symptoms. It is important to investigate underlying cause of MINOCA. Thorough history is the key to diagnosis.

RESUMEN

SUMMARY: Anaplastic transformation of a primary thyroid tumor whose process can be followed is rare. The objective this study is to report a case of anaplastic transformation of locally advanced papillary thyroid carcinoma after treatment with lenvatinib. A 74-year-old woman consulted a local physician because of cough and bloody sputum. Thyroid cancer with tracheal invasion was suspected on computed tomography (CT) imaging, and she visited our hospital for treatment. We suspected anaplastic thyroid cancer (ATC) and core needle biopsy was performed. Histologic sections of the core needle biopsy showed that the tumor formed a papillary structure, and we diagnosed papillary thyroid carcinoma. Surgery would have been difficult, and we initiated lenvatinib at a low dose of 8 mg/day. CT on day 40 of lenvatinib treatment revealed that the thyroid tumor had shrunk remarkably. CT on day 111 revealed that tumor regrowth and tracheal invasion had been exacerbated. Core needle biopsy was performed, and histologic sections of the core needle biopsy that was performed after regrowth of the tumor showed that individual cancer cells had large, irregular nuclei, and necrosis was also observed. The immunohistochemical findings were negative for thyroglobulin, and only a few cells were positive for thyroid transcription factor 1, and we diagnosed ATC. Anaplastic transformation of the target lesion may be one of the causes of lenvatinib treatment failure in differentiated thyroid carcinoma. LEARNING POINTS: Anaplastic transformation of a primary thyroid tumor whose process can be followed is rare. The resistance mechanism of lenvatinib in treatment for differentiated thyroid carcinoma has not been clarified. Anaplastic transformation of the target lesion may be one of the causes of lenvatinib treatment failure in differentiated thyroid carcinoma.

RESUMEN

SUMMARY: A 21-year-old woman was referred to our hospital to treat bilateral pheochromocytomas (PCCs) after a diagnosis of multiple endocrine neoplasia type 2A (MEN2A). We performed bilateral laparoscopic adrenalectomy. One year after the operation, urinary fractionated metanephrines in 24-h urine increased. MRI showed a 30 mm tumor on the interaortocaval region and 123I-MIBG concentrated in this area. We excised the tumor and performed para-aortic lymphadenectomy. Histopathologic examination confirmed a PCC arising from ectopic adrenal tissue. Urinary fractionated metanephrines in 24-h urine declined to basal levels immediately after the operation. We detected no recurrence of paraganglioma or PCC for 5 years after the treatment. LEARNING POINTS: Most ectopic adrenal tissue is associated with no symptoms and contains only the adrenal cortex. Adrenocortical tumors sometimes arise from ectopic adrenal tissues similarly to in the normal adrenal gland. PCC arising from ectopic adrenal tissue occurs infrequently. MEN2-related PCC is accompanied by adrenal medullary hyperplasia, which might be part of tumorigenesis.

RESUMEN

SUMMARY: Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy. LEARNING POINTS: PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade. Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities. Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease. PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases.

RESUMEN

SUMMARY: Patients treated with immunosuppressive drugs, especially methotrexate (MTX), rarely develop lymphoproliferative disorders (LPDs), known as MTX-related LPD (MTX-LPD). The primary site of MTX-LPD is often extranodal. This is the first reported case of MTX-LPD in the pituitary. A 65-year-old woman was admitted to our hospital with symptoms of oculomotor nerve palsy and multiple subcutaneous nodules. She had been treated with MTX for 11 years for rheumatoid arthritis. Computed tomography showed multiple masses in the orbit, sinuses, lung fields, anterior mediastinum, kidney, and subcutaneous tissue. Brain magnetic resonance imaging revealed a sellar mass. She was diagnosed with hypopituitarism and central diabetes insipidus based on endocrine examination. Although pituitary biopsy could not be performed, we concluded that the pituitary lesion was from MTX-LPD, similar to the lesions in the sinuses, anterior mediastinum, and subcutaneous tissue, which showed polymorphic LPD on biopsy. MTX was discontinued, and methylprednisolone was administered to improve the neurologic symptoms. After several weeks, there was marked improvement of all lesions, including the pituitary lesion, but the pituitary function did not improve. When pituitary lesions are caused by MTX-LPD, the possibility of anterior hypopituitarism and central diabetes insipidus needs to be considered. Further studies are needed to investigate the effectiveness of early diagnosis and treatment of MTX-LPD in restoring pituitary dysfunction. LEARNING POINTS: Pituitary lesions from MTX-LPD may cause hypopituitarism and central diabetes insipidus. Pituitary metastasis of malignant lymphoma and primary pituitary lymphoma, which have the same tissue types with MTX-LPD, have poor prognosis, but the lesions of MTX-LPD can regress only after MTX discontinuation. In cases of pituitary lesions alone, a diagnosis of MTX-LPD may be difficult, unless pituitary biopsy is performed. This possibility should be considered in patients treated with immunosuppressive drugs. Pituitary hypofunction and diabetes insipidus may persist, even after regression of the lesions on imaging due to MTX discontinuation.

RESUMEN

SUMMARY: A 42-year-old man with complaints of muscle soreness and an increased pigmentation of the skin was referred because of a suspicion of adrenal insufficiency. His adrenocorticotropic hormone and cortisol levels indicated a primary adrenal insufficiency (PAI) and treatment with hydrocortisone and fludrocortisone was initiated. An etiological workup, including an assessment for anti-adrenal antibodies, very long-chain fatty acids, 17-OH progesterone levels and catecholamine secretion, showed no abnormalities. 18Fluorodeoxyglucose positron emission tomography/CT showed bilateral enlargement of the adrenal glands and bilateral presence of an adrenal nodule, with 18fluorodeoxyglucose accumulation. A positive tuberculin test and positive family history of tuberculosis were found, and tuberculostatic drugs were initiated. During the treatment with the tuberculostatic drugs the patient again developed complaints of adrenal insufficiency, due to insufficient dosage of hydrocortisone because of increased metabolism of hydrocortisone. LEARNING POINTS: Shrinkage of the adrenal nodules following tuberculostatic treatment supports adrenal tuberculosis being the common aetiology. The tuberculostatic drug rifampicin is a CYP3A4 inducer, increasing the metabolism of hydrocortisone. Increase the hydrocortisone dosage upon initiation of rifampicin in case of (adrenal) tuberculosis. A notification on the Addison's emergency pass could be considered to heighten physician's and patients awareness of hydrocortisone drug interactions.

RESUMEN

SUMMARY: A 67-year-old woman with a past history of type 2 diabetes mellitus presented with worsening glycemic control. She had some acromegaly symptoms and magnetic resonance imaging demonstrated a pituitary tumor. Endocrinological examination found the resting growth hormone (GH) level within the normal range, but elevated insulin-like growth factor 1 level. A 75 g oral glucose tolerance test showed inadequate suppression of nadir GH levels. Acromegaly due to GH-secreting pituitary tumor was diagnosed. The patient underwent endoscopic transsphenoidal surgery resulting in gross total removal of the tumor and recovered well postoperatively. Histological examination of the tumor showed coexistence of relatively large gangliocytoma cells and pituitary adenoma cells, suggesting mixed gangliocytoma-pituitary adenoma. In addition, colocalization of GH and GH-releasing hormone (GHRH) in pituitary adenoma cells was revealed, so the adenomatous components were more likely to produce GHRH in our mixed gangliocytoma-pituitary adenoma case. Mixed gangliocytoma-pituitary adenoma is very rare, and the present unique case demonstrated only the adenomatous components associated with GHRH production. LEARNING POINTS: Sellar gangliocytoma coexisting with pituitary adenoma is recognized as a mixed gangliocytoma-pituitary adenoma and is very rare. A proposed developmental mechanism of growth hormone (GH)-secreting mixed gangliocytoma-pituitary adenoma involves GH-releasing hormone (GHRH) produced by the gangliocytic components promoting the growth of tumor including GH-secreting adenomatous components. Since our present case indicated that the adenomatous components of mixed gangliocytoma-pituitary adenoma could secrete both GH and GHRH simultaneously, progression of GH-secreting mixed gangliocytoma and pituitary adenoma may involve exposure to spontaneously produced GHRH due to the adenomatous components.