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Background: In the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) single-arm phase 2 trial, concomitant chemotherapy and selective internal radiotherapy (SIRT) showed antitumor activity as a first-line treatment of unresectable intrahepatic cholangiocarcinomas (ICCs). In this sub-analysis, we aimed to evaluate one of the secondary endpoints, the health-related quality of life (QoL), evaluated with an EORTC QLQ-C30 instrument at the baseline and during treatment. Methods: The MISPHEC trial included treatment-naïve patients with an unresectable ICC between November 2013 and June 2016. Patients received concomitant first-line chemotherapy with cisplatin and gemcitabine for 8 cycles, SIRT was administered during cycle 1 (for patients with unilobar disease) or cycles 1 and 3 (for patients with bilobar disease) using glass Yttrium-90 microspheres. We evaluated the QoL—measured by the QLQ-C30 questionnaire—at the baseline, every 8 weeks during chemotherapy and follow-up, between 12 and 15 weeks after embolization and every 12 weeks after a liver resection if applicable. Results: A total of 41 patients were included, of which 34 completed questionnaires at the baseline. No clinically significant changes in the global health score or the sub-scales of the QLQ-C30 were observed during follow-up. The physical, social and role function mean score worsened during treatment and fatigue, nausea and pain scores increased although the differences were not clinically significant. In patients undergoing subsequent surgery, the QoL was not impaired. Conclusions: A combination of SIRT and chemotherapy with gemcitabine and cisplatin as the first-line treatment of unresectable ICCs was found to maintain the QoL.

In the FIGHTDIGO study, digestive cancer patients with dynapenia experienced more chemotherapy-induced neurotoxicities. FIGHTDIGOTOX aimed to evaluate the relationship between pre-therapeutic handgrip strength (HGS) and chemotherapy-induced dose-limiting toxicity (DLT) or all-grade toxicity in digestive cancer patients. HGS measurement was performed with a Jamar dynamometer. Dynapenia was defined according to EWGSOP2 criteria (

Background After thyroidectomy some patients experience a chronic fatigue syndrome called asthenia. The purpose of this study was to determine the post-operative health related quality of life (HRQOL) and risk of asthenia in patients undergoing thyroidectomy. Methods A single institution prospective observational cohort study of adults undergoing thyroidectomy from September 2016 to July 2019 with four HRQOL surveys: preoperative baseline, 2 wk-, 6 mo- and 12 mo-postoperatively. Patients were surveyed using the Short Form 36 version 2 and Brief Fatigue Inventory. Asthenia was defined as Brief Fatigue Inventory > 60 at 12 mo. HRQOL was compared between patients undergoing thyroid lobectomy (TL) or total thyroidectomy (TT) with benign (-B) or malignant (-Ca) final pathology. Results A total of 182 patients were included: 67 (37%) with TL-B, 32 (17%) with TL-Ca, 40 (22%) with TT-B, and 43 (24%) with TT-Ca. The incidence of asthenia was 42% for TT and 4% for TL. In the TL-B group, 2 patients (3%) developed asthenia, compared with 2 patients (6.25%) in the TL-Ca group, 14 patients (35%) in the TT-B group, and 21 (48.8%) in the TT-Ca group (P = 0.0001). The odds ratio of asthenia for TT compared to TL was 10.4 (95% CI 3.86-28.16) and for patients with malignancy compared to benign disease was 2.05 (95% CI 1.17-3.61). Conclusions Patients undergoing TT have a higher risk of developing asthenia than those undergoing TL, particularly if the final pathology shows malignancy.

Trifluridine/tipiracil increases overall survival (OS) in patients with refractory, metastatic colorectal cancer (mCRC). A post hoc exploratory analysis of the RECOURSE randomized clinical trial (RCT) established two categories, a good prognosis corresponding to subjects having a low tumor burden and indolent disease. Other models in refractory mCRC are the FAS-CORRECT and Colon Life nomogram. The main objective was to externally validate the prognostic factors of the RECOURSE and FAS-CORRECT trials, and the Colon Life nomogram in a multicenter, real-world series of mCRC treated in 3rd and successive lines with trifluridine/tipiracil. The secondary aim was to develop an OS predictive model, TAS-RECOSMO. Between 2016 and 2019, 244 patients were recruited. Median OS was 8.15 vs 8.12 months for the poor (85% of the subjects) and good (15%) prognosis groups from the RESOURCE trial, respectively, log-rank p = 0.9. The most common grade 3–4 toxicities were neutropenia (17%), asthenia (6%), and anemia (5%). The AFT lognormal model TAS-RECOSMO included six variables: ECOG-PS, KRAS/NRAS/BRAF mutation status, time between diagnosis of metastasis and beginning of trifluridine/tipiracil, NLR, CEA, and alkaline phosphatase. The model’s bootstrapped bias-corrected c-index was 0.682 (95% CI, 0.636–0.722). The factors from the Colon Life model, FAS-CORRECT, and RECOURSE displayed a c-index of 0.690, 0.630, and 0.507, respectively. TAS-RECOSMO, FAS-CORRECT, and the Colon Life nomogram appear to predict OS in patients with refractory mCCR who begin trifluridine/tipiracil treatment in the real world. The prognostic groups of the RECOURCE RCT were unable to capture the situation of real-world subjects treated with trifluridine/tipiracil in this series.

The clinical and immunological study of the potential impact of coronavirus infection on the course of endogenous psychosis.Thirty-three female patients, aged 16 to 48 years, with depressive-delusional conditions (ICD-10 F20.01, F21, F31) developed after coronavirus infection, of whom 15 people (group 1) had depressive-delusional states 1-2 months after COVID-19 and 18 people (group 2), who developed similar psychoses in later periods (2-6 months). The severity of the psychopathologic symptoms was evaluated with PANSS and HDRS-21 scales. The activity of inflammatory markers - leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) in the blood was determined. The absolute neutrophil count, the absolute lymphocyte count and the neutrophil/lymphocyte ratio were calculated. As a control, we used standard values of indicators of age - and sex-matched healthy donors.The endogenous psychosis that developed later after a coronavirus infection (group 2) is associated with a "typical" inflammatory reaction with an increase in the activity of acute phase proteins (according to α1-PI) and degranulation activity of neutrophils (according to LE), which is associated with the development of depressive-delusional states in patients with the dominance of manifestations of positive affectivity (anxiety, melancholy) and the extended nature of delusional disorders, which were predominantly incongruent to affect. On the contrary, the development of endogenous psychosis during the first two months after COVID-19 (group 1) is characterized by a spectrum of inflammatory biomarkers with a decrease in the number of neutrophils and low activity of LE. This immunological profile is associated with the predominance of manifestations of negative affectivity (apathy, asthenia, adynamia) in the structure of depressive-delusional states and the relatively undeveloped nature of delusional disorders, which were predominantly congruent to affect.The clinical and biological correlates presumably indicate the modulating effect of the coronavirus infection (COVID-19) on neuroinflammation and the structure of endogenous psychosis.Клинико-иммунологическое исследование потенциального влияния коронавирусной инфекции на течение эндогенных психозов.Обследованы 33 пациентки в возрасте от 16 до 48 лет с депрессивно-бредовыми состояниями (F20.01, F21, F31), развившимися после перенесенной коронавирусной инфекции, из них 1-я группа — 15 человек, у которых депрессивно-бредовое состояние развилось через 1—2 мес после перенесенного COVID-19; 2-я группа — 18 человек с подобными психозами, развившимися в более поздние (от 2 до 6 мес) сроки. Выраженность психопатологических симптомов оценивали по шкалам PANSS и HDRS-21. В крови пациентов определяли активность воспалительных маркеров — лейкоцитарной эластазы (ЛЭ) и α1-протеиназного ингибитора (α1-ПИ). Оценивали также абсолютное содержание нейтрофилов и лимфоцитов и их соотношение (нейтрофильно-лимфоцитарный индекс). В качестве контроля использовали нормативные значения показателей здоровых доноров, соответствующих пациентам по возрасту и полу.Показано, что эндогенный психоз, развившийся в более поздние сроки после перенесенной коронавирусной инфекции (2-я группа) сопряжен с «типичной» воспалительной реакцией с повышением активности острофазных белков (α1-ПИ — 43,0 (35,6—49,7) ИЕ/мл,Выявленные клинико-биологические корреляты предположительно свидетельствуют о модулирующем влиянии перенесенного COVID-19 на нейровоспаление и структуру эндогенного психоза.

Objectives To describe the clinical evolution and predictors of symptom persistence during 2 months' follow-up in adults with noncritical coronavirus disease 2019 (COVID-19). Methods We performed descriptive clinical follow-up (day (D) 7, D30 and D60) of 150 patients with noncritical COVID-19 confirmed by real-time reverse transcriptase PCR at Tours University Hospital from 17 March to 3 June 2020, including demographic, clinical and laboratory data collected from the electronic medical records and by phone call. Persisting symptoms were defined by the presence at D30 or D60 of at least one of the following: weight loss ≥5%, severe dyspnoea or asthenia, chest pain, palpitations, anosmia/ageusia, headache, cutaneous signs, arthralgia, myalgia, digestive disorders, fever or sick leave. Results At D30, 68% (103/150) of patients had at least one symptom; and at D60, 66% (86/130) had symptoms, mainly anosmia/ageusia: 59% (89/150) at symptom onset, 28% (40/150) at D30 and 23% (29/130) at D60. Dyspnoea concerned 36.7% (55/150) patients at D30 and 30% (39/130) at D60. Half of the patients (74/150) at D30 and 40% (52/130) at D60 reported asthenia. Persistent symptoms at D60 were significantly associated with age 40 to 60 years old, hospital admission and abnormal auscultation at symptom onset. At D30, severe COVID-19 and/or dyspnoea at symptom onset were additional factors associated with persistent symptoms. Conclusions Up to 2 months after symptom onset, two thirds of adults with noncritical COVID-19 had complaints, mainly anosmia/ageusia, dyspnoea or asthenia. A prolonged medical follow-up of patients with COVID-19 seems essential, whatever the initial clinical presentation.

The aim: To examine the features of depressive and anxiety phenomenology in lung cancer, taking into account the gender factor.Materials and methods: 112 patients with a primary diagnosis of stage II and III lung cancer were clinically and psychologically examined using HDRS, HARS, BDI, C. Spilberger's Reactive and Personality Anxiety Scale.Results: It was found that the core affective psychopathological symptoms of patients with lung cancer are manifestations of depression (96.3% of men, 96.8% of women (p0.05), 96.4% together) and anxiety (77.8% , 93.5% (p0.05) and 82.1%) in combination with asthenic-neurotic (67.9%, 61.3% (p0.05) and 66.1%) and affective labile (54.3%, 61.3% (p0.05) and 56.2%) manifestations; additional symptoms are apathetic (25.9%, 9.7% (p0.05) and 21.4%), obsessive (19.8%, 38.7% (p0.05) and 25.0%) and dysphoric (23.5%, 6.5% (p0.05) and 18.7%) manifestations. The severity of depressive and anxiety of women is higher than of men; the severity of depressive-anxiety manifestations corresponds to a moderate level: depression by HDRS - 11.6±1.7 points, 15.6±6.3 points (p0.05) and 12.7±4.0 points; BDI depression - 15.7±6.3 points, 23.7±13.9 points (p0.05) and 17.9±9.7 points; HARS anxiety - 9.3±2.8 points, 11.5±3.7 points (p0.05) and 9.9±3.2 points, and reactive anxiety - 44.4±11.1 points, 47.9±15.5 points (p0.05) and 45.4±12.5 points. The identified differences can be explained by different gender models of psychological response.Conclusions: The core affective symptoms of patients with lung cancer are manifestations of depression and anxiety in combination with asthenic-neurotic and affective-labile manifestations; additional are apathetic, obsessive and dysphoric manifestations.

To know the factors associated with an unfavorable evolution (UE) of patients diagnosed with COVID-19 with total or partial follow-up in primary care.A case series.Urban health center.By systematic sampling, patients ≥18 years, diagnosed with COVID-19, with analytical confirmation, in 2020 and followed up by their family doctors, were selected.Dependent variable: hospital admission or death due to COVID-19.age, sex, medical background, clinical data and treatments related to the disease. Statistical analysis, with SPSS 25.0: descriptive analysis, comparison of proportions (chi square) and medians (Mann-Whitney U). The analysis is completed with logistic regression.610 patients were included in the study. The median age was 49 years (interquartile range: 35-61); 51.8% were women; 14.9% presented UE (95% CI: 12.0-17.8). The sociodemographic variables or the variables related to medical background that showed an independent association with UE were age (OR: 1.066; 95% CI: 1.038-1.095), sex (OR for men: 3.277; 95% CI: 1.304-8.235) and being a smoker or former smoker (OR: 2.565; 95% CI: 1.135-5.800). Regarding the clinical variables of the disease, an association was found for altered consciousness (OR: 62.829; 95% CI: 9.177-430.149), dyspnea (OR: 14.339; 95% CI: 6.046-34.009), expectoration (OR: 4.764; 95% CI: 1.858-12.213)) and asthenia (OR: 3.993; 95% CI: 1.705-9.351).14.9% of the patients diagnosed with COVID-19 presented an UE. Older age, male sex and being a smoker or former smoker increased the probability of it. Altered consciousness, dyspnea, expectoration, and asthenia were the clinical data that best predicted UE.

Background and ObjectivesPrevious studies suggested that autoimmune limbic encephalitis with antibodies against contactin-associated protein-like 2 (CASPR2-encephalitis) is clinically heterogeneous and progresses slowly, preventing its early recognition. We aimed to describe the onset and progression of CASPR2-encephalitis and to assess long-term outcomes.MethodsWe retrospectively analyzed the medical records of all patients whose CSF tested positive for anti-CASPR2 antibodies in our center between 2006 and 2020. Standardized telephone interviews of all available patients and relatives were conducted, assessing long-term functional independence using the Functional Activity Questionnaire (FAQ) and quality of life using the 36-Item Short-Form Survey (SF36).ResultsForty-eight patients were included (98% males; median age 64 years), and 35 participated in telephone interviews (73%). At onset, 81% had at least 1 neurologic symptom among the following: limbic (54%), peripheral nerve hyperexcitability (PNH; 21%), and/or cerebellar symptoms (17%). Most of the patients (75%) had initially symptoms of only one of these categories. Limbic symptoms at onset included mostly seizures (33%), while memory disturbances were less frequent (10%). PNH signs were mostly neuropathic pain (9/10 patients). Other symptoms seen at onset included asthenia (33%), mood disorders (25%), and insomnia (21%); 19% of patients did not show any limbic, peripheral, or cerebellar symptom at onset but only asthenia (15%), mood disorders (6%), weight loss (8%), dysautonomia (4%), and/or insomnia (2%). The peak of the disease was attained in median 16.7 months after onset. Over the study period (median follow-up, 58.8 months, range 10.6–189.1), 77% of patients developed ≥3 core CASPR2 symptoms and 42% fulfilled the diagnostic criteria for autoimmune limbic encephalitis, although all patients ultimately developed limbic symptoms. At the last visit, most interviewed patients (28/35 patients, 80%; median, 5 years after onset) had recovered functional independence (FAQ p= 0.0369).DiscussionCASPR2-encephalitis has a progressive course and is highly heterogeneous at the early stage. In men older than 50 years, otherwise unexplained seizures, cerebellar ataxia, and/or neuropathic pain are suggestive of early-stage CASPR2-encephalitis, especially if they coincide with recent asthenia, mood disorders, or insomnia.

Purpose Chronic spontaneous urticaria (CSU) is defined as urticaria and/or angioedema that appears spontaneously due to known or unknown causes and lasts for at least 6 weeks. Omalizumab, an anti-IgE antibody that binds circulating free IgE, has recently emerged as a promising treatment for CSU, a condition which impairs patients' quality of life. We aimed to contribute real life data by reporting our experience with omalizumab in the treatment of intractable CSU. Methods of 140 patients treated with omalizumab in our clinic between September 2013 and January 2018, 86 CSU patients with available current data were retrospectively evaluated in terms of sex, age, urticaria duration, urticaria activity score over 7 days (UAS7) before and after omalizumab, relapses and time to relapse, length of remission after omalizumab cessation, adverse events, and comorbidities. Results the mean age of the patients was 45.5 +/- 14.3 years and 73.3% were women. Mean duration of urticaria before initiation of omalizumab therapy was 54.5 +/- 67 months. All patients had used antihistamines before starting omalizumab treatment. the mean number of omalizumab doses was 11.9 +/- 9.3. the mean duration of omalizumab treatment was 13.3 +/- 10.4 months. Mean UAS7 score was 38.9 +/- 4.1 before the start of omalizumab treatment, and 7.9 +/- 10.5 after treatment. Treatment was discontinued in 10 patients (11.6%) due to nonresponse or loss of effect. Four patients (4.65%) experienced adverse events. Treatment was discontinued in 1 patient (1.16%) due to side effects. of the 55 patients whose treatment was discontinued after their symptoms resolved, 31 (56.3%) relapsed after omalizumab cessation. Twenty-four patients (43.6%) did not relapse after omalizumab cessation. Conclusions Our results show that omalizumab was an effective treatment for intractable CSU and did not cause any serious adverse effects other than asthenia, vertigo, and injection site reaction in four patients. These findings are relevant because they reflect real-life data.

Background: The clinical characteristics of the most frequent arbovirosis (Dengue, Zika, Chikungunya) are very similar, which is a diagnostic challenge for clinicians. Objective: To identify the presence of clinical characteristics related to Zika virus infection confirmed by the laboratory in patients during an epidemic of co-infection with Zika and Dengue viruses. Method: Cross-sectional descriptive study of patients with clinical - epidemiological suspicion of Zika virus infection, who were admitted in the Hospital “Joaquín Albarrán” (La Habana, Cuba), during June 1 to October 31 of 2017. Demographic and symptoms and signs were recorded. By PCR for Zika virus (in blood or urine) the disease was confirmed. Results: 1541 patients were studied. The most frequent symptoms and signs were rash (93.8%), pruritus (77.9%), arthralgia (60.0%), headache (50.8%), myalgia (46.1%), fever (34.7%), asthenia (31.7%), and conjunctivitis (27.9%). Zika virus infection was confirmed in 279 patients (18.1%). Greater frequency of arthralgia, asthenia, and diarrhea was demonstrated in Zika confirmed patients. Conclusion: Minor clinical relevance was observed in the symptoms or signs of arboviral disease to support the clinical diagnosis of Zika virus infections by clinician during a Zika-Dengue epidemic. The assessment of the temporality of the onset of Zika and Dengue symptoms of these infections is recommended to assist clinicians in the differential diagnosis. Keywords: Non-specific febrile syndrome, Zika, Infection, Clinical picture, Cuba

Summary Adrenocortical carcinoma (ACC) is an aggressive cancer that originates in the cortex of the adrenal gland and generally has a poor prognosis. ACC is rare but can be more commonly seen in those with cancer predisposition syndromes (e.g. Li-Fraumeni and Lynch Syndrome). The diagnosis of ACC is sometimes uncertain and it requires the use of precise molecular pathology; the differential diagnosis includes pheochromocytoma, adrenal adenoma, renal carcinoma, or hepatocellular carcinoma. We describe a case of a 57-year-old woman with Lynch Syndrome and metastatic ACC who was initially diagnosed as having pheochromocytoma. The tumor was first identified at 51 years of age by ultrasound followed by a CT scan. She underwent a left adrenalectomy, and the histopathology identified pheochromocytoma. Two years later, she had tumor recurrence with imaging studies showing multiple lung nodules. Following a wedge resection by video-assisted thoracoscopic surgery (VATS), histopathology was read as metastatic pheochromocytoma at one institution and metastatic ACC at another institution. She later presented to the National Institutes of Health (NIH) where the diagnosis of ACC was confirmed. Following her ACC diagnosis, she was treated with mitotane and pembrolizumab which were stopped due to side effects and progression of disease. She is currently receiving etoposide, doxorubicin, and cisplatin (EDP). This case highlights the importance of using a multi-disciplinary approach in patient care. Thorough evaluation of the tumor’s pathology and analysis of the patient’s genetic profile are necessary to obtain the correct diagnosis for the patient and can significantly influence the course of treatment. Learning points: Making the diagnosis of ACC can be difficult as the differential diagnosis includes pheochromocytoma, adrenal adenoma, renal carcinoma, or hepatocellular carcinoma. Patients with Lynch Syndrome should undergo surveillance for ACC as there is evidence of an association between Lynch Syndrome and ACC. Conducting a complete tumor immunoprofile and obtaining a second opinion is very important in cases of suspected ACC in order to confirm the proper diagnosis. A multi-disciplinary approach including genetic testing and a thorough evaluation of the tumor’s pathology is imperative to ensuring that the patient receives an accurate diagnosis and the appropriate treatment.

We performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone - from doublets to the triplet FOLFOXIRI - in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged50 years) and to explore whether EO-mCRCs have a peculiar tumour genomic profiling.Subgroup analyses according to age (50 versus ≥50 years) and treatment (FOLFOXIRI/bev versus doublets/bev) were carried out for rates of any grade and grade ≥3 (≥G3) overall and singular adverse events, progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Tumour genomic profiling was obtained using a DNA-based next-generation sequencing platform.Of 1187 patients included, 194 (16%) patients were aged50 years. Females were more frequently diagnosed with EO-mCRC (P = 0.04). Patients aged50 years showed a lower risk of ≥G3 neutropenia (P = 0.07), diarrhoea (P = 0.04), asthenia (P = 0.008) and a higher risk of any grade nausea (P 0.01) and vomiting (P 0.01). Patients receiving FOLFOXIRI/bev more frequently experienced ≥G3 chemotherapy-related adverse events respect to doublets/bev, regardless of age (PUpfront FOLFOXIRI/bev shows a favourable efficacy/safety balance in EO-mCRC.Clinicaltrials.gov Identifiers NCT00719797, NCT0233-9116.

In March 2020, the World Health Organization (WHO) declared a pandemic for coronavirus 19. Typical symptoms were fever, cough, asthenia, dyspnea, and muscle pain. Pulmonary and central nervous system compromise presented challenging characteristics for healthcare physicians. The objectives of this study were to identify epidemiological and clinical characteristics of SARS-COV-2 infection survivors in a region of Argentina and to determine differences between gender, age groups, year of infection, and evolution time since diagnosis.A descriptive and analytical cross-sectional observational study was carried out. A self-administered questionnaire was applied, which was available between August and December 2021.Among 1868 individuals included, the mean age was 39.4 ± 13.9 years, and 72.8% were female. Arterial hypertension was the most frequent comorbidity (11.7%). The majority were outpatients (81.9%). The most frequent presentation symptoms at all ages were asthenia (83.7%), fever (54.9%), headache (60.8%), anosmia (64.8%), ageusia (53.2%), cough (54.4%) and myalgias (53.7%). For the 18 to 29 years old age group, the most prevalent presentation symptoms were: headache (69.4%), anosmia (69.1%), ageusia (60.2%), odynophagia (45%), and rhinitis/nasal congestion (46.9%). In the 30 to 64 years old age group, there was a higher prevalence of myalgias (55.8%), arthralgias (41%), and concentration/memory disorder (28.3%). Male showed higher prevalence of fever (64.9% versus 51.1%; p0.001) and pneumonia (23.5% versus 13.4%; p0.001). After 12 weeks from diagnosis, 38.1% of patients persisted with asthenia, 23.6% with anosmia/dysosmia, and 21.2% with concentration/memory disorders.Systemic symptoms were common to all age groups with coronavirus 19 disease; however, younger, and intermediate age groups presented a higher prevalence of central nervous system symptoms such as anosmia and cognitive disorders, respectively. Symptoms beyond 12 weeks of diagnosis reached slightly more than 10% of the participants.En marzo de 2020 la enfermedad por coronavirus 19 fue declarada pandemia por la Organización Mundial de la Salud. Los síntomas más comunes fueron fiebre, tos, astenia, disnea y dolor muscular. Los compromisos pulmonar y del sistema nervioso central presentaron características desafiantes para los médicos asistenciales. Los objetivos del estudio fueron conocer las características epidemiológicas y clínicas de sobrevivientes a infección por SARS-CoV-2 en una región de Argentina, y determinar las diferencias entre género, grupos etarias, año de contagio, tiempo de evolución desde el diagnóstico.Se realizó un estudio observacional descriptivo y analítico de corte transversal. Se aplicó un cuestionario auto administrado, que estuvo disponible entre agosto y diciembre de 2021.La media de edad fue de 39,4 ± 13,9 años, el 72,8% fueron mujeres. La comorbilidad más frecuente fue hipertensión arterial (11,7%). La mayoría de los pacientes fueron ambulatorios (81,9%). Los síntomas de presentación más frecuentes a cualquier edad, fueron astenia (83,7%), fiebre (54,9%), cefalea (60,8%), anosmia (64,8%), ageusia (53,2%), tos (54,4%) y mialgias (53,7%). Para el grupo de 18 a 29 años los síntomas de presentación más prevalentes fueron cefalea (69,4%), anosmia 69,1%), ageusia (60,2%), odinofagia (45%) y rinitis/congestión nasal (46,9%). En el grupo de 30 a 64 años se observó mayor prevalencia de mialgias (55,8%), artralgias (41%), falta de concentración/memoria (28,3%). Los hombres mostraron más prevalencia de fiebre (64,9% versus 51,1%; p0,001) y neumonía (23,5% versus 13,4%; p0,001). Luego de las 12 semanas del diagnóstico 38,1% de los pacientes persistían con astenia, 23,6% con anosmia/disosmia y 21,2% con trastornos de concentración/memoria.La enfermedad por coronavirus 19 presenta un patrón de síntomas sistémicos común a todos los grupos etarios. No obstante, los grupos más jóvenes presentan más prevalencia de síntomas de afección del sistema nervioso central como la anosmia y los grupos intermedios, mayor prevalencia de trastornos cognitivos. Los síntomas más allá de las 12 semanas del diagnóstico alcanzaron a algo más del 10% de los participantes.

Many studies have investigated post-COVID symptoms, but the predictors of symptom persistence remain unknown. The objective was to describe the natural course of the disease at 6 months and to identify possible factors favoring the resurgence or persistence of these symptoms. COVEVOL is a retrospective observational descriptive study of 74 patients. All patients with positive SARS-CoV-2 PCR from March 2020 were included. We compared a group with symptom persistence (PS group) with another group without symptom persistence (no-PS group). Fifty-three out of seventy-four patients (71.62%) described at least one persistent symptom at 6 months of SARS-CoV-2 infection. In the PS group, 56.6% were women and the average age was 54.7 years old [21–89.2] ± 16.9. The main symptoms were asthenia (56.6%, n = 30), dyspnea (34%, n = 18), anxiety (32.1% n = 17), anosmia (24.5%, n = 13) and agueusia (15.1% n = 8). Ten patients (13.51%) presented a resurgence in symptoms. Patients in the PS group were older (p = 0.0048), had a higher BMI (p = 0.0071), and were more frequently hospitalized (p = 0.0359) compared to the no-PS group. Odynophagia and nasal obstruction were less present in the inaugural symptoms of COVID-19 in the PS group (p = 0.0202 and p = 0.0332). Persistent post-COVID syndromes are common and identification of contributing factors is necessary for understanding this phenomenon and appropriate management.

Aim: We report real-world evidence with regorafenib in previously treated metastatic colorectal cancer from the French cohort of the international, prospective, observational CORRELATE study. Patients & methods: Patients receiving regorafenib according to French health authority approval were included. The primary end point was treatment-emergent adverse events. Overall survival and progression-free survival were secondary end points. Results: Two hundred and forty-two patients (61% male, median age: 66 years) were enrolled. The most common grade ≥3 drug-related treatment-emergent adverse events were hand–foot skin reaction (10.3%), asthenia/fatigue (9.9/1.2%) and hypertension (6.2%). Median overall survival and progression-free survival were 6.8 (95% CI: 6.3–7.6) and 2.8 months (95% CI: 2.6–3.0), respectively. Conclusion: The real-world safety and effectiveness data of regorafenib in metastatic colorectal cancer in France align with findings from Phase III clinical trials and the global CORRELATE population.

To describe persistent symptoms in long COVID-19 non-severe outpatients and report the 6-month clinical recovery (CR) rate.Observational study enrolling outpatients (≥ 18 years) with confirmed non-severe COVID-19 (positive nasopharyngeal RT-PCR or presence of SARS-CoV-2 antibodies) who consulted for persistent symptoms after the first pandemic wave (March-May 2020). CR was assessed at the 6-month visit and defined as complete (no symptom), partial (persistent symptoms of lower intensity) or lack of recovery (no improvement).Sixty-three patients (79% women, mean age: 48 years) enrolled; main symptoms (mean 81 days after acute infection): asthenia/myalgia (77%), dyspnea (51%), headaches (35%), cough (33%). At 6 months (n=56), 30% had complete, 57% partial, and 13% lack of recovery. The proportion of patients with2 persistent symptoms was 26% at 6 months (main symptoms: dyspnea [54%] and asthenia/myalgia [46%]).We observed a slow but high recovery rate at 6 months among these outpatients.

We performed a prospective cohort study of 311 outpatients with non-severe COVID-19 (187 women, median age 39 years). Of the 214 (68.8%) who completed the 6-week follow-up questionnaire, 115 (53.7%) had recovered. Others mostly reported dyspnea (n = 86, 40.2%), weight loss (n = 83, 38.8%), sleep disorders (n = 68, 31.8%), and anxiety (n = 56, 26.2%). Of those who developed ageusia and anosmia, these symptoms were still present at week 6 in, respectively, 11/111 (9.9%) and 19/114 (16.7%). Chest CT scan and lung function tests found no explanation in the most disabled patients (n = 23). This study confirms the high prevalence of persistent symptoms after non-severe COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04261-y.

This observational, prospective study assessed, in a daily clinical practice, the molecular response, safety, quality of life (QoL) and treatment adherence in 183 patients with chronic myeloid leukaemia in chronic phase (CML-CP), receiving nilotinib as first-line treatment. Premature study termination before 24 months of follow-up occurred in 61 patients (33·3%), and was essentially due to nilotinib treatment discontinuation (n = 53; 29%), motivated by treatment intolerance (n = 29; 15·8%) and inefficacy (n = 19; 10·4%). After 24 months of treatment, 112/122 patients (91·8%) had a molecular assessment, 95·5% of whom achieved a major molecular response (MMR), 32·1% achieved uMR4 , defined as an undetectable molecular disease with 4-log molecular response sensitivity (≥10 000 ABL1 transcripts). The Morisky Green Levine Medication Adherence Scale was completed by 94/122 patients (77·0%), and 89·4% of these patients obtained a satisfactory level of treatment adherence, defined as a score ≥3. Patients' QoL was good at baseline and stable during the follow-up period. The two most common nilotinib-related adverse events (AEs) were pruritus (14·8%) and asthenia (13·7%). Seven patients (3·8%) experienced at least one cardiovascular ischaemic AE. This French nationwide cohort study provides relevant information in daily clinical practice indicating that nilotinib is a valuable first-line treatment option for CML-CP patients.

Introduction Pirfenidone was the first antifibrotic drug approved in Argentina for idiopathic pulmonary fibrosis (IPF). Outcomes in real life may differ from the results of clinical trials. The primary endpoint was to study the tolerance of pirfenidone in real life. Secondary endpoints were to analyze effectiveness and reasons for discontinuation. Materials and methods Retrospective observational study conducted in four specialized centers in Argentina. We analyzed the medical records of patients with IPF who received pirfenidone between June 2013 and September 2016. Adverse events (AE) and the variables that could influence these results were analyzed. Forced vital capacity (FVC%) parameters were also compared between the pre-pirfenidone and post-pirfenidone periods. Results Fifty patients were included, 38 (76%) men, with mean age (SD) 67.8 (8.36) years. Mean (SD) exposure to pirfenidone was 645.68 (428.19) days, with a mean daily dose (SD) of 2064.56 mg (301.49). Nineteen AEs in 15 patients (30%) were reported: nausea (14%), asthenia (10%) and skin rash (8%). A total of 18 patients (36%) interrupted treatment, only 1 definitively. The most frequent reason for discontinuation was failure of suppliers to provide the drug (9 subjects; 18%). We compared the evolution of FVC% between the pre-pirfenidone and post-pirfenidone periods, and found a mean (SD) FVC% decline of 4.03% (7.63) pre-pirfenidone and 2.64% (7.1) post-pirfenidone (P=.534). Conclusions In our study, pirfenidone was well tolerated and associated with a reduction in FVC decline, although without reaching statistical significance.

To determine the structure and mechanisms of interaction of asthenic disorders with negative and positive psychopathological symptoms in hypochondriac schizophrenia.The study included male and female patients, aged 17-69 years, with a diagnosis of hypochondriac schizophrenia (F20.80 according to ICD-10) and asthenia symptoms. The main research method was clinical, which was supplemented by pathopsychological examination and the use of psychometric scales (PANSS, SANS, MFI-20,VAS asthenia).Asthenia in case of hypochondriac schizophrenia (schizoasthenia) integrates two unrelated phenomena: «weakness» and «exhaustion» (intolerance to stress), and also acts within the framework of three psychopathological syndromes: neurotic, senestopathic/hypochondriac and overvalued hypochondria. Asthenia with hypochondriac schizophrenia is a predictor of an unfavorable social and clinical prognosis. Integrating into the structure of the clinical manifestations of hypochondriac schizophrenia, asthenia forms close relationships with positive and negative disorders of the type of «general syndromes», but remains outside the categories of both positive and negative symptoms of the disease, thus forming a separate «dimension» in the psychopathological space of schizophrenia.Определение структуры и механизмов взаимодействия астенических расстройств с психопатологическими симптомами негативного и позитивного ряда при ипохондрической шизофрении.В исследовании участвовали пациенты мужского и женского полов в возрасте 17—69 лет с диагнозом ипохондрической шизофрении (F20.80 по МКБ-10) и явлениями астении. Основным методом исследования был клинический, который дополнялся патопсихологическим обследованием и применением психометрических шкал (PANSS, SANS, MFI-20, ВАШ астении).В проведенной работе было выявлено, что астения при ипохондрической шизофрении (шизоастения) интегрирует два нерядоположенных феномена: «слабость» и «истощаемость» (интолерантность к нагрузкам), а также выступает в рамках трех психопатологических синдромов: невротической, сенестоипохондрической и сверхценной ипохондрии. Астения при ипохондрической шизофрении — предиктор неблагоприятных социального и клинического прогнозов. Интегрируясь в структуру клинических проявлений ипохондрической шизофрении, астения образует тесные взаимосвязи с позитивными и негативными расстройствами по типу «общих синдромов», но остается вне категорий как позитивных, так и негативных симптомов заболевания, формируя, таким образом, отдельную «дименсию» в психопатологическом пространстве шизофрении.

Introduction: in women with breast cancer and gynecologic cancer, as well as in men with prostate carcinoma, hot flashes, asthenia, and insomnia are common and bothersome symptoms that impair quality of life. Objective: to evaluate the effectiveness of tryptophan intake as a treatment for hot flushes, asthenia, and insomnia in patients with prostate, breast, and uterine cervical cancer. Materials and methods: intervention study without a control group at the HUCA Radiation Oncology Service, from July 2018 to July 2019. A total of 60 patients with prostate, breast, or uterine cervical cancer who had received treatment with radiotherapy and hormone therapy, and who presented with hot flushes, asthenia, and insomnia were included. L-tryptophan was administered at a dose of 3 g per day. Results: a significant increase in serum tryptophan levels at the end of the study (p0.001) and a significant decrease in the scores of the study symptoms were reported. Although statistical significance was not found, a significant improvement in each symptom was observed, as well as an improvement in quality of life (p0.001). Conclusions: the study suggests that, in patients with breast, prostate, or uterine cervical cancer, and symptoms such as hot flushes, asthenia, and insomnia, the administration of tryptophan as a nutritional supplement is well tolerated, improves quality of life, and is associated with improvement in the scale scores of the symptoms of interest, although no statistically significant relationship with increased blood tryptophan levels was found.Introducción: tanto en las mujeres con cáncer de mama y cáncer ginecológico como en los hombres con carcinoma prostático, los sofocos, la astenia y el insomnio son síntomas frecuentes y molestos que alteran la calidad de vida. Objetivo: evaluar la eficacia del aporte de triptófano como tratamiento de los sofocos, la astenia y el insomnio en pacientes con cáncer de próstata, de mama y cervicouterino. Materiales y métodos: estudio de intervención sin grupo de control en el Servicio de Oncología Radioterápica del HUCA, en el período de julio de 2018 a julio de 2019. Se incluyeron en total 60 pacientes con cáncer de próstata, de mama y cervicouterino que habían recibido tratamiento con radioterapia y hormonoterapia, y que presentaban sofocos, astenia e insomnio. Se administraron 3 g de L-triptófano al día. Resultados: se reportan un aumento significativo del valor del triptófano sérico al final del estudio (p0,001) y una disminución significativa de las puntuaciones de los síntomas estudiados; aunque no hemos hallado ninguna significación estadística entre ellos, sí se aprecia una mejoría significativa de cada uno de los síntomas, así como una mejoría de la calidad de vida (p0,001). Conclusiones: el estudio actual sugiere que, en los pacientes con cáncer de mama, de próstata o cervicouterino y síntomas de sofocos, astenia e insomnio, el aporte de triptófano como suplemento nutricional se tolera bien, mejora la calidad de vida y puede asociarse a una mejoría de los valores obtenidos en las escalas de los síntomas referidos, aunque no se demuestra ninguna relación estadísticamente significativa con la elevación del triptófano en sangre.

International audience; Objective: To investigate the clinical features of patients who had two demonstrated coronavirus disease 2019 (COVID-19) episodes. Methods: Data of patients with both COVID-19 episodes were recruited from 22 March to 27 December 2020. The following outcomes were studied: epidemiological, comorbidities, prevalence and severity of general and otolaryngological symptom, olfactory, aroma, and gustatory dysfunctions. A comparison between first and second episodes was performed. Results: Forty-five patients reported having two confirmed COVID-19 episodes. The majority of patients had mild infections in both episodes. The second clinical episode was significantly similar to the first. The symptom duration of the second episode was shorter than the first. The occurrence of loss of smell was unpredictable from the first to the second episode. Conclusion: The recurrence of COVID-19 symptoms is associated with a similar clinical picture than the first episode in patients with initial mild-to-moderate COVID episode. The pathophysiological mechanisms underlying the development of second episode remain uncertain and may involve either true reinfection or virus reactivation from sanctuaries.

Though the exact etiology of autoimmune diseases still remains not completely known, there are various factors which are known to contribute to be trigger of autoimmune diseases. Viral infection is known to be among the other. It is known as the infection from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) can be an autoimmune trigger, so, we suppose that SARS-Coronavirus (SARS-CoV-2) could be as well. Several authors have highlighted the temporal consequence between SARS-CoV-2 and autoimmune diseases. In this case report we described a patient admitted for COVID-19 pneumonia with completely negative autoimmunity at admission who developed major pulmonary interstitial disease. During the hospitalization the weaning difficulties from oxygen led us to the repetition of autoimmunity pattern which became positive (both during hospitalization then after two months from dismission) with marked positivity for specific antibodies for myositis even after the patient's infectious healing. In the follow-up, the patient continued to have asthenia and muscle weakness despite steroid therapy. She is still in follow-up and will be further evaluated over time. Can we therefore think that in this case the development of autoimmunity can persist beyond the infectious phase and determine over time the development of a real autoimmune myositis?

An observational and descriptive study including patients discharged for COVID-19 was carried out by the COVID-19 Working Group of the Hospital Clínico San Carlos (HCSC). We aimed to identify the main symptoms after 90 days of hospital discharged. A structured interview was conducted, through a “checklist” that included symptoms within the 90 days post-discharge. A total of 134 patients were enrolled. The most frequently referred symptoms were asthenia, dyspnea and weight loss. Anxiety was the most frequent psychological symptom found through the GAD-7 scale.

Background The neurological effects of Lyme borreliosis in children are varied and their clinical progression is not widely reported in the French literature. We carried out a retrospective study to describe the clinical characteristics of Lyme neuroborreliosis in children in southwest France and their clinical progression at 6 months. Methods This study was carried out at Toulouse University Hospital during the period 2006–2017 using patient records. Case definition was based on the combined French clinical and laboratory diagnostic criteria. Results In total, 26 children were included. The median age was 8 years (4–14 years). The different neurological symptoms reported were: meningoradiculitis (62%), which was usually associated with facial palsy (54%); isolated facial palsy (15%); isolated meningitis (8%); polyradiculoneuritis (4%); benign intracranial hypertension (4%) and myelomeningoradiculitis (4%). The most common functional symptoms were headaches (54%), the perception of asthenia (42%), neck pain (27%), and a loss of appetite (19%). Patients with laboratory meningitis (84%) often had no signs of meningism or headaches (38%). Conclusion The majority of the cases involved meningoradiculitis but other, less common, neurological conditions have been described. The clinical signs suggestive of meningitis are not very marked and might delay the diagnosis.

To assess the efficacy of sequential therapy with Mexidol and Mexidol FORTE 250 in comparison with placebo in patients of different age groups with chronic brain ischemia.The study is sub-analysis of data of the international multicenter, randomized, double-blind, placebo-controlled study of sequential therapy in patients with chronic brain ischemia (MEMO), which included 318 patients (25% men) in the age of 40-90 (median 60) years. All subjects were subdivided into 3 age subgroups: 40-60 years (After 75 days of treatment positive dynamic was revealed in cognitive, emotional and motor impairment in patients of 40-60 and 61-75 age subgroups both in groups of Mexidol and placebo, but in group of Mexidol the changes were more prominent which is proved by significantly higher values of median of absolute difference of total score of studied parameters.The results of trial showed that in patients of different age-subgroups with chronic brain ischemia the improvement in cognitive, motor impairment and quality of life, as well as decrease in vegetative impairment, asthenia and anxiety are observed after 75 days of treatment both in Mexidol and placebo group, but in Mexidol group these changes are more prominent. The data obtained confirm the expediency of the use of sequential therapy with Mexidol and Mexidol FORTE 250 in patients of different age subgroups with chronic brain ischemia.Оценить эффективность последовательной терапии препаратами Мексидол и Мексидол ФОРТЕ 250 в сравнении с плацебо у пациентов с хронической ишемией головного мозга (ХИМ) разных возрастных подгрупп.Представлен субанализ данных международного многоцентрового рандомизированного двойного слепого плацебо-контролируемого исследования МЕМО, в котором участвовали 318 пациентов (25% мужчин) в возрасте от 40 до 90 (медиана 60) лет. Эффективность лечения оценивалась в трех возрастных группах: 40—60 (Положительная динамика выраженности когнитивных, эмоциональных и двигательных нарушений в группах 40—60 и 61—75 лет через 75 дней терапии была выявлена у больных, получавших как Мексидол, так и плацебо, однако у пациентов, получавших Мексидол, эти изменения оказались более выраженными, на что указывают более высокие значения медианы абсолютной разницы суммы баллов изучаемых показателей.Результаты исследования показали, что у пациентов с ХИМ значимо более выраженное улучшение когнитивных и двигательных функций, повышение качества жизни, уменьшение выраженности вегетативных нарушений, астении и тревожности через 75 дней терапии наблюдались на фоне применения Мексидола по сравнению с плацебо. Полученные результаты свидетельствуют о целесообразности применения Мексидола для лечения пациентов разного возраста с ХИМ.

Hereditary myopathy with early respiratory failure is a neuromuscular disease with an autosomal dominant inheritance pattern. Clinical presentation is characterised by proximal and distal muscle weakness, exertional dyspnoea and generalised fatigue. There is no disease-modifying therapy and the prognosis is unknown. Herein we present a case of a 40-year-old woman with long-standing asthenia and apathy and, more recently, daytime sleepiness, dyspnoea and difficulty in walking. A hypercapnic respiratory failure with severe acidemia was identified. The muscle biopsy showed the presence of cytoplasmatic bodies and rimmed vacuoles, suggestive of a hereditary myopathy with early respiratory failure disease. The genetic study confirmed this diagnosis identifying a heterozygous mutation on c.95134T>C (p.Cys31712Arg) in exon 343 in the titin gene. The patient was discharged home under supportive treatment with non-invasive ventilation.

This is an analysis of clinical characteristics, images findings, laboratory variables and respiratory mechanics in patients with coronavirus disease 2019 (COVID-19) during the first month of the pandemic outbreak in Buenos Aires. In this descriptive case study of a single-centre, we included all confirmed cases of COVID-19 hospitalized in intensive care unit (ICU). All cases were confirmed by reverse transcription polymerase chain reaction. A total of 7 patients with confirmed COVID-19 were referred to out ICU. The median age was 71 years (interquartile range 52-75), including 4 men and 3 women. Patients most common clinical manifestations were fever (7), cough (5), asthenia (4) and shortness of breath (3). Among the radiological findings, five of them showed interstitial opacities and one patient had bilateral pulmonary consolidation. Five required invasive mechanical ventilation and multiple prone sessions. None died during hospitalization, although three still remain in the ICU. According to imaging examination, 71.4% showed interstitial opacities and one patient bilateral consolidation. Five patients required invasive mechanical ventilation and multiple prone sessions. None of them died during hospitalization, although three still remain in the ICU.Se trata de un análisis de características clínicas, hallazgos radiológicos, variables de laboratorio y mecánica respiratoria en pacientes con enfermedad por coronavirus 2019 (COVID-19) durante el primer mes de la pandemia en Buenos Aires. Es un estudio descriptivo de casos, de un solo centro. Se incluyeron todos los casos confirmados de COVID-19 internados en la unidad de terapia intensiva de adultos (UTIA) del Hospital Italiano de Buenos Aires. Todos los casos se confirmaron por reacción en cadena de la polimerasa con transcriptasa inversa. Un total de 7 pacientes con COVID-19 fueron atendidos en la UTIA. La mediana de edad fue de 71 años (intervalos intercuartílicos: 52-75), 4 hombres y 3 mujeres. Las manifestaciones clínicas más comunes fueron fiebre (7), tos (5), astenia (4) y disnea (3). Entre los hallazgos radiológicos, cinco de ellos mostraron opacidades intersticiales y un paciente consolidación pulmonar bilateral. Cinco requirieron ventilación mecánica invasiva y múltiples sesiones de decúbito prono. Ninguno murió durante la hospitalización, aunque aún tres permanecen en UCI.

Summary Isolated, adult-onset central hypothyroidism is very rare, and its diagnosis can be challenging. A 42-year-old patient was referred for evaluation of a 2.8 cm thyroid nodule. She referred symptoms that could be attributed to hypothyroidism and thyroid tests showed low TSH and normal-low levels of free T4. However, evaluation of the remaining pituitary hormones and pituitary MRI were normal, yet a radionuclide scanning revealed that the thyroid nodule was ‘hot’ and the tracer uptake in the remaining thyroid tissue was suppressed. Interpretation of these studies led to a misdiagnosis of subclinical hyperthyroidism and the patient was treated with radioiodine. Soon after treatment, she developed a frank hypothyroidism without appropriate elevation of TSH and the diagnosis of central hypothyroidism was made a posteriori. Long term follow-up revealed a progressive pituitary failure, with subsequent deficiency of ACTH and GH. This case should alert to the possibility of overlooking central hypothyroidism in patients simultaneously bearing primary thyroid diseases able to cause subclinical hyperthyroidism. Learning points: Although rarely, acquired central hypothyroidism can occur in the absence of other pituitary hormone deficiencies. In these cases, diagnosis is challenging, as symptoms are unspecific and usually mild, and laboratory findings are variable, including low, normal or even slightly elevated TSH levels, along with low or low-normal concentrations of free T4. In cases with low TSH levels, the coexistence of otherwise common disorders able to cause primary thyroid hyperfunction, such as autonomous nodular disease, may lead to a misdiagnosis of subclinical hyperthyroidism.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) led to the death of thousands of people around the world.1 Neurologic manifestations are not much specific apart from acute anosmia, and postinfectious manifestation data are missing.2 We described the cases of 2 patients exhibiting demyelinating form of Guillain-Barre syndrome (GBS) and summarized neurologic manifestations and investigations results in table 1.

Summary Multiple endocrine metastases are a rare but possible complication of lung adenocarcinoma (LAC). Pituitary metastasis is a rare condition with poor clinical expression. Diabetes insipidus (DI) is its most common presenting symptom. Here we report an original case of a pituitary stalk (PS) metastasis from LAC presenting as central DI followed by adrenal insufficiency (AI) from bilateral adrenal metastasis, without known evidence of the primary malignancy. A 45-year-old woman whose first clinical manifestations were polyuria and polydipsia was admitted. She was completely asymptomatic with no cough, no weight loss or anorexia. Chest radiography was normal. Brain MRI showed a thick pituitary stalk (PS). DI was confirmed by water restriction test and treated with vasopressin with great clinical results. Explorations for systemic and infectious disease were negative. Few months later, an acute AI led to discovering bilateral adrenal mass on abdominal CT. A suspicious 2.3 cm apical lung nodule was found later. Histopathological adrenal biopsy revealed an LAC. The patient received systemic chemotherapy with hormonal replacement for endocrinological failures by both vasopressin and hydrocortisone. We present this rare case of metastatic PS thickness arising from LAC associated with bilateral adrenal metastasis. Screening of patients with DI and stalk thickness for lung and breast cancer must be considered. Multiple endocrine failures as a diagnostic motive of LAC is a rare but possible circumstance. Learning points: Adrenal metastasis is a common location in lung adenocarcinoma; however, metastatic involvement of the pituitary stalk remains a rare occurrence, especially as a leading presentation to diagnose lung cancer. The posterior pituitary and the infundibulum are the preferential sites for metastases, as they receive direct arterial blood supply from hypophyseal arteries. Patients diagnosed with diabetes insipidus due to pituitary stalk thickness should be considered as a metastasis, after exclusion of the classical systemic and infectious diseases. The diagnosis of an endocrinological metastatic primary lung adenocarcinoma for patients without respiratory symptoms is often delayed due to a lack of correlation between endocrinological symptoms and lung cancer. The main originality of our case is the concomitant diagnosis of both endocrinological failures, as it was initiated with a diabetes insipidus and followed by an acute adrenal insufficiency.

To assess the formation of positive personality phenomena in patients with mild cognitive impairment and asthenic syndrome during the treatment with recognan (citicoline).Thirty-eight patients (17 men and 21 women), aged 18 to 45 years (mean age 27.8±12.1 years), with asthenic syndrome with mild cognitive impairment (ICD-10 F06.7) were examined. Patients were divided into two groups: 20 people in the main group and 18 people in the comparison group. The main group received recognan (orally, in solution, 100 mg in 1 ml) for 30 days, the daily dosage of the drug was 0.5 g (5 ml solution). The comparison group did not receive any medications. Adapted methods of positive personality psychology were used: the Fordyce Emotions Questionnaire, the Subjective Happiness Scale (SHS), the Adult Hope Scale (AHS), the Satisfaction with Life Scale (SWLS), M. Atkinson's Scale of Emotional Maturity, the projective technique 'Map of experiences'. The follow-up period was 30 days. All subjects were examined three times (at baseline, 15 and 30 days after treatment).After a month of treatment with recognan, there was an improvement of positive personality traits and a significant decrease in negative experiences, indicating the positive impact of the drug on the formation of positive personality manifestations and compensation for emotional disorders in patients with mild cognitive impairment and asthenic syndrome.Цель исследования. Оценка особенностей формирования позитивных личностных феноменов у пациентов с легкими когнитивными нарушениями и астеническим синдромом, а также их динамики в процессе использования препарата Рекогнан (цитиколин). Материал и методы. Обследовали 38 пациентов,17 мужчин и 21 женщину, в возрасте от 18 до 45 лет (средний возраст 27,8±12,1 года), у которых диагностирован астенический синдром с легкими когнитивными расстройствами (рубрика F06.7 по МКБ-10). Больные были разделены на две группы: 20 человек в основной группе и 18 человек в группе сравнения. Основная группа получала лечение препаратом Рекогнан (перорально, в растворе, 100 мг в 1 мл) в течение 30 дней, суточная дозировка препарата составляла 0,5 г (5 мл раствора). В группе сравнения лекарственную терапию не проводили. Для оценки состояния больных и личностных изменений применяли следующие психологические тесты и шкалы: 'Эмоциональный тест Фордайса', 'Шкала субъективного счастья', 'Шкала надежды', 'Шкала эмоциональной зрелости М. Аткинсона', 'Шкала удовлетворенности жизнью', проективная методика 'Карта переживаний'. Период наблюдения составил 30 дней. Все испытуемые были обследованы 3 раза (до начала исследования, на 15-й и 30-й дни). Результаты и заключение. После месячного курса лечения Рекогнаном отмечено улучшение показателей по шкалам, направленным на оценку позитивных изменений личности, а также достоверное уменьшение негативных переживаний, что свидетельствовало о положительном влиянии препарата на формирование у больных с легкими когнитивными нарушениями при астеническом синдроме позитивных личностных проявлений и компенсацию эмоциональных нарушений.

Gitelman syndrome is one of the salt losing tubulopathies. Hypokalemia and hypomagnesemia appear in the setting of the partial blockade of salt absorption in the distal tubule. We conducted a descriptive study of a case series of five patients with Gitelman syndrome (4 women, from 28 to 85 years) in our institution, between the years 2004 and 2015. The most frequent form of diagnosis in our series was by laboratory finding. The only acknowledged clinical symptom was malaise. Regarding laboratory findings, the mean potassemia was of 2.5 ± 0.5 mmol/l, with a minimum value of 2.1 mmol/l. Additionally, the serum magnesium value was of 1.3 ± 0.3 mg/dl. In conclusion, we observed that the forms of presentation consist of biochemical alterations with or without nonspecific manifestations, which currently represents the greatest diagnostic difficulty and reinforces the importance to achieve a timely diagnosis, especially in young patients with critical serum potassium values.El síndrome de Gitelman forma parte de las denominadas tubulopatías perdedoras de sal. El bloqueo parcial de la reabsorción de sodio en el túbulo contorneado distal determina la aparición de hipokalemia e hipomagnesemia. Se realizó un estudio descriptivo de una serie de cinco casos de síndrome de Gitelman (4 mujeres, de 28 a 85 años de edad) atendidos en nuestra institución entre los años 2004 y 2015. La forma de diagnóstico más frecuente en nuestra serie fue por hallazgo de laboratorio. El único síntoma clínico manifestado en forma espontánea fue astenia. En cuanto a los valores de laboratorio, la potasemia fue 2.5 ± 0.5 mmol/l, con un valor mínimo de 2.1. Adicionalmente, el valor de magnesio en sangre fue 1.3 ± 0.3 mg/dl. Como conclusión, observamos que las formas de presentación consisten en alteraciones bioquímicas con o sin manifestaciones inespecíficas, lo que representa actualmente la mayor dificultad diagnóstica y refuerza la importancia de lograr un diagnóstico oportuno, en especial en pacientes jóvenes y con valores críticos de potasio sérico.

Children and adolescents with hematological diseases are constantly in a state of prolonged psychological stress caused by hospitalization, debilitating treatment, lifestyle changes, which ultimately leads to a significant reduction in the quality of life. In this connection it is necessary to study the dynamics of mental and emotional condition of the child at different stages of chemotherapy and the timing of formation of asthenic syndrome.Determine the presence of psycho-emotional disorders and the severity of asthenic syndrome in children with acute leukemia after the first stage of chemotherapy in order to further predict the development of this pathology and develop a package of solutions that minimize its manifestations.A survey of 36 children was conducted, of them 21 people aged 6–10 years old, 15 people aged 11–16 years old. There are 27 boys (75%) and 9 girls (25%). The survey was conducted on the 78th day of the ALL IC-BFM 2009 protocol, which corresponds to the end of the first phase of chemotherapy. In the survey did not participate children with the syndrome of multiple organ failure, as well as with the presence of background mental disorders. To assess the psycho-emotional state, a questionnaire was used: “state of health, activity, mood”, adapted for children. For the study of asthenia was used questionnaire I. K. Schatz.The findings suggest that absolutely all children receiving chemotherapy at the end of the first phase have been violations of the psycho-emotional background. The index of state of health suffers the most, and to a lesser extent - activity. Indicators of state of health had lower values in the older group - from 11 to 16 years. Thus according to the data in the group of children aged 6 to 10 years being the average was 4.02 ± 0.09 (p0.05), in children age 11 - 16 years - 3.83 ± 0.11 (p0.05). The average activity substantially the same in groups and indicates a favorable condition. Mood indicators are also within the framework of a favorable state in both groups. Also during the investigation revealed that the general for all children is a symptom asthenic. According to the data, fatigue reaction (less than 7 points) was present only in 9 children (25%). The most numerous manifestations were moderate asthenia - 21 children (58%). Severe asthenia (13 - 18 points) was observed only in 6 children (17%).This study will allow to develop a package of solutions for the prevention and minimization of asthenic syndrome in children with acute leukemia receiving chemotherapy.

Background Antibiotics are overused in patients with acute lower respiratory tract infections (ALRTIs), but less is known about their use in patients with asthma, or the use of asthma medication for ALRTI in patients without asthma. Our aim was to describe the frequency, variation and drivers in antibiotic and asthma medication prescribing for ALRTI in adults with and without asthma in primary care. Methods A retrospective cohort analysis of patients aged ≥12 years, diagnosed with an ALRTI in primary care in 2014–15 was conducted using data from the Clinical Practice Research Datalink. Current asthma status, asthma medication and oral antibiotic use within 3 days of ALRTI infection was determined. Treatment frequency was calculated by asthma status. Mixed-effect regression models were used to explore between-practice variation and treatment determinants. Results There were 127,976 ALRTIs reported among 110,418 patients during the study period, of whom 17,952 (16%) had asthma. Respectively, 81 and 79% of patients with and without asthma received antibiotics, and 41 and 15% asthma medication. There were significant differences in between-practice prescribing for all treatments, with greatest differences seen for oral steroids (odds ratio (OR) 18; 95% CI 7–82 and OR = 94; 33–363, with and without asthma) and asthma medication only (OR 7; 4–18 and OR = 17; 10–33, with and without asthma). Independent predictors of antibiotic prescribing among patients with asthma included fewer previous ALRTI presentations (≥2 vs. 0 previous ALRTI: OR = 0.25; 0.16–0.39), higher practice (OR = 1.47; 1.35–1.60 per SD) and prior antibiotic prescribing (3+ vs. 1 prescriptions OR = 1.28; 1.04–1.57) and concurrent asthma medication (OR = 1.44; 1.32–1.57). Independent predictors of asthma medication in patients without asthma included higher prior asthma medication prescribing (≥7 vs. 0 prescriptions OR = 2.31; 1.83–2.91) and concurrent antibiotic prescribing (OR = 3.59; 3.22–4.01). Conclusion Findings from the study indicate that antibiotics are over-used for ALRTI, irrespective of asthma status, and asthma medication is over-used in patients without asthma, with between-practice variation suggesting considerable clinical uncertainty. Further research is urgently needed to clarify the role of these medications for ALRTI.

Multiple Chemical Sensitivity (MCS) is a chronic and/or recurrent condition with somatic, cognitive, and affective symptoms following a contact with chemical agents whose concentrations do not correlate with toxicity in the general population. Its prevalence is not well defined, it mainly affects women between 40 and 50 years, without variations in ethnicity, education and economic status. We aimed to assess the core symptoms of this illness in a sample of Italian patients. Two physicians investigated different symptoms with a checklist compilation in 129 patients with MCS (117 women). We conducted a categorical Principal Component Analysis (CATPCA) with Varimax rotation on the checklist dataset. A typical triad was documented: hyperosmia, asthenia, and dyspnoea were the most common symptoms. Patients also frequently showed cough and headache. The CATPCA showed seven main factors: 1, neurocognitive symptoms, 2, physical (objective) symptoms, 3, gastrointestinal symptoms, 4, dermatological symptoms, 5, anxiety-depressive symptoms, 6, respiratory symptoms, 7, hyperosmia and asthenia. Patients showed higher mean prevalence of factors 7 (89.9%), 6 (71.7%), and 1 (62.13%). In conclusion, MCS patients frequently manifest hyperosmia, asthenia, and dyspnoea, which are often concomitant with other respiratory and neurocognitive symptoms. Considering the clinical association that is often made with anxiety, more studies are necessary on the psychosomatic aspects of this syndrome. Further analytical epidemiological studies are needed to support the formulation of aetiological hypotheses of MCS.

Purpose: Limited treatment options are available for patients with advanced non-small cell lung cancer (NSCLC) after failure of first-line platinum-based chemotherapy. The treatment of recurrent advanced NSCLC progressed with the arrival of nivolumab and other immunotherapeutic agents. Our single-center prospective study aimed to present the effectiveness and safety of nivolumab in second-line setting after first-line platinum doublet in Indian patients with advanced NSCLC. Patients and Methods: Twenty-nine adult patients with stage IV NSCLC treated with nivolumab after failure of first-line platinum-based chemotherapy at Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, India, between October 2016 and January 2018, were included in the study. Overall survival (OS), hematological, and nonhematological toxicities were evaluated. Results: A total of 29 patients (mean age of 59.6 years at enrollment) were evaluated. Histological evaluation revealed adenocarcinoma (44.8%) and squamous (55.2%) type of cancer. The Eastern Cooperative Oncology Group performance score was II in 7 patients (24.1%) and I in 22 (75.9%) patients. Patients received an average of four cycles of nivolumab. The median survival duration was 101 days, and OS rate in the study was 51.7%. Six patients (20.7%) had stable disease response, five patients (17.2%) had partial response, and three patients (10.3%) were lost to follow-up. Asthenia and cough were the most common nonhematological toxicities. Only three patients developed hematological toxicities (anemia and thrombocytopenia). Conclusion: Data from our study suggest nivolumab is well-tolerated and effective in Indian patients with recurrent advanced NSCLC after failure of the multiple first lines of platinum-based combination chemotherapy.

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

Aim To explore the feasibility and activity of oral metronomic vinorelbine patients with advanced NSCLC not eligible to standard chemotherapy because of old age (≥70 years), and/or poor Eastern Cooperative Oncology Group performance status (≥2), and/or extensive brain or bone disease, and/or active comorbidities (≥2) requiring for pharmacological treatment. Patients and methods In a prospective phase II not randomized study, patients with stage IV NSCLC unfit to chemotherapy were treated with oral metronomic vinorelbine at 30 mg fixed dose three times a week until disease progression. Results Fifty patients were treated, 19 (38%) in the first-line setting. Five patients (11%) experienced a grade 3 toxicity; no grade 4 toxicity occurred. Overall disease control rate was 32%, 44% and 26% in first and subsequent lines, respectively (p=0.39). Median OS and PFS were 7.3 months (95% confidence interval [CI]=4.7-10.0) and 2.7 months (95%CI=2.0-3.4), respectively. Conclusion These data support the activity and safety of metronomic vinorelbine in a relevant proportion of patients usually excluded from any specific treatment.

Background: This phase Ib study evaluated afatinib plus vinorelbine in patients with advanced solid tumours overexpressing epidermal growth factor receptor (EGFR) and/or human EGFR 2 (HER2). Methods: Maximum tolerated doses (MTDs) were determined for afatinib (20, 40 or 50 mg, once daily) combined with standard intravenous vinorelbine (part A; 25 mg m−2 per week) or oral vinorelbine (part B; 60 mg m−2 per week, increased to 80 mg m−2 per week at week 3). Secondary end points for expanded MTD cohorts included assessments of safety, pharmacokinetics, tumour response and progression-free survival (PFS). Results: The afatinib MTD was 40 mg with intravenous (MTDA) and oral (MTDB) vinorelbine. The most frequent cycle 1 dose-limiting toxicities were febrile neutropenia and diarrhoea, consistent with individual safety profiles of vinorelbine and afatinib. Common treatment-related adverse events included: diarrhoea (92.7%), asthenia (76.4%), nausea (63.6%), neutropenia (56.4%) and vomiting (54.5%). No notable pharmacokinetic interactions were observed. Best overall tumour response was stable disease in part A (16 out of 28 patients), and partial response in part B (3 out of 27 patients). Median PFS was 14.6 and 15.9 weeks for patients treated at the MTDA and MTDB, including dose-escalation and expansion cohorts. Conclusions: Afatinib in combination with intravenous or oral vinorelbine demonstrated a manageable safety profile and antitumour activity at the MTD of 40 mg per day.

Background In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. Methods Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 + R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT-RAS patients. Results Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WT-RAS: 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab-FOLFIRI (WT-RAS: 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT-RAS: 37%/69%). The R0-R1 resection rate was 34%/46% (WT-RAS:26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: [0.6–1.5]; WT-RAS:13/15; HR: 0.7 [0.4–1.3]). Median OS was 37/41 months (HR:1.0 [0.6–1.8]; WT-RAS: 39/49; HR:0.9 [0.4–1.9]). In WT-RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS ≥ 30%/ ≥ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p = 0.003) and neuropathy (13%/0%; p = 0.025) in the Pmab-FOLFOX4 arm. Conclusions In patients with WT-KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and Pmab-FOLFIRI resulted in high ORR and ETS, allowing potentially curative resection. No significant differences in efficacy were observed between the two regimens. (clinicaltrials.gov: NCT00885885 ).

OBJECTIVE To compare biomechanical and histologic features of heart valves and echocardiographic findings between Quarter Horses with and without heritable equine regional dermal asthenia (HERDA). DESIGN Prospective case-control study. ANIMALS 41 Quarter Horses. PROCEDURES Ultimate tensile strength (UTS) of aortic and mitral valve leaflets was assessed by biomechanical testing in 5 horses with HERDA and 5 horses without HERDA (controls). Histologic evaluation of aortic and mitral valves was performed for 6 HERDA-affected and 3 control horses. Echocardiography was performed in 14 HERDA-affected and 11 control horses. Biomechanical data and echocardiographic variables of interest were compared between groups by statistical analyses, RESULTS Mean values for mean and maximum UTS of heart valves were significantly lower in HERDA-affected horses than in controls. Blood vessels were identified in aortic valve leaflets of HERDA-affected but not control horses. Most echocardiographic data did not differ between groups. When the statistical model for echocardiographic measures was controlled for body weight, mean and maximum height and width of the aorta at the valve annulus in short-axis images were significantly associated with HERDA status and were smaller for affected horses. CONCLUSIONS AND CLINICAL RELEVANCE Lower UTS of heart valves in HERDA-affected horses, compared with those of control horses, supported that tissues other than skin with high fibrillar collagen content are abnormal in horses with HERDA. Lack of significant differences in most echocardiographic variables between affected and control horses suggested that echocardiography may not be useful to detect a substantial loss of heart valve tensile strength. Further investigation is warranted to confirm these findings. Studies in horses with HERDA may provide insight into cardiac abnormalities in people with collagen disorders.