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BACKGROUND: Gastrointestinal (GI) bleeding is a leading cause of intensive care unit (ICU) admission in pancreatic cancer patients. AIMS: To analyze causes, ICU mortality and hemostatic treatment success rates of GI bleeding in pancreatic cancer patients requiring ICU admission. METHODS: Retrospective multicenter cohort study between 2009 and 2021. Patients with a recent pancreatic resection surgery were excluded. RESULTS: Ninety-five patients were included (62 % males, 67 years-old). Fifty-one percent presented hemorrhagic shock, 41 % required mechanical ventilation. Main GI bleeding causes were gastroduodenal tumor invasion (32 %), gastroesophageal varices (21 %) and arterial aneurysm (12 %). Arterial aneurysms were more frequent in patients with previous pancreatic resection (36 % vs 2 %, p < 0.001). Hemostatic procedures included gastroduodenal endoscopy in 81 % patients and arterial embolization in 28 % patients. ICU mortality was 19 %. Multivariate analysis identified four variables associated with mortality: performance status >2 (OR 9.34, p = 0.026), mechanical ventilation (OR 14.14, p = 0.003), treatment success (OR 0.09, p = 0.010), hemorrhagic shock (OR 11.24, p = 0.010). Treatment success was 46 % and was associated with aneurysmal bleeding (OR 29.89, p = 0.005), ongoing chemotherapy (OR 0.22, p = 0.016), and prothrombin time ratio (OR 1.05, p = 0.001). CONCLUSION: In pancreatic cancer patients with severe GI bleeding, early identification of aneurysmal bleeding (particularly in case of previous resection surgery) and coagulopathy management may increase the treatment success and reduce mortality.

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Genetic variations among people mainly determine the blood levels of lipoprotein (a) (Lp(a)), and it is relatively stable throughout one's lifetime. Nevertheless, there could still be other factors that control the Lp(a) level. Thyroid hormones are known to influence the serum lipid level by regulating the expression of key enzymes that are involved in lipid metabolism. Both hypo and hyperthyroidism are associated with changes in lipid levels. Even though thyroid hormone abnormalities have been shown to alter traditional lipid parameters like low-density lipoprotein (LDL-C), its influence on Lp(a) has not been established. This review aims to identify the relationship between Lp(a) and thyroid hormones by reviewing data from correlative studies and observing treatment-related Lp(a) level changes in thyroid disorders from interventional studies. We searched MEDLINE, Cochrane, and Google Scholar databases with predefined search criteria and search strategies for paper identification. Individual reviewers reviewed identified papers for selection. Finalized papers were reviewed for Lp(a) levels and their responses to treatment in patients with thyroid disorders to establish the relationship between Lp(a) and thyroid hormone. We concluded that the data were limited and sometimes contradicted one another to establish a clear relationship between Lp(a) and thyroid hormones. Even though correlative studies data showed strong indications that overt-hypothyroidism was associated with high Lp(a) levels, thyroid hormone replacement studies did not show any significant changes in Lp(a) levels compared to pre-treatment in patients with both overt-hypothyroidism and subclinical hypothyroidism. More clinical trials focusing on Lp(a) with longer periods of treatment and follow-up in thyroid patients are needed to establish the relationship between the two. The possibility of dose-related Lp(a) responses to thyroid hormone treatment should also be explored.

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Within the realms of human and artificial intelligence, the concepts of consciousness and comprehension are fundamental distinctions. In the clinical sphere, patient awareness regarding medication and its physiological processes plays a crucial role in determining drug efficacy and outcomes. This article introduces a novel perspective on prescription practices termed "Ultra-Overt Therapy" (UOT). A review of current supporting evidence was conducted through a non-systematic search in PubMed and Google Scholar, focusing on concepts such as the "mind-body relationship," "placebo response," "neuroscience," and "complementary medicine." Our findings, rooted in the mechanisms of the "placebo effect," the intricacies of "intersubjective therapy," the potency of "interoceptive awareness," and other domains of medical science, suggest that UOT holds theoretical promise. Future research endeavors focusing on these areas may elucidate the global impact of this method on medical treatment and patient care.

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Objectives: To determine the incidence of overt diabetes in pregnancy (ODIP) among women with 50-g GCT results ≥ 200 mg/dL and compare characteristics and pregnancy outcomes between women with and without gestational diabetes (GDM). Methods: A retrospective cohort study was conducted in 212 pregnant women whose 50-g GCT results ≥ 200 mg/dL. ODIP was diagnosed from 75-g OGTT if fasting plasma glucose ≥ 126 and/or 2-h plasma glucose ≥ 200 mg/dL. Various characteristics and pregnancy outcomes were compared between ODIP and those with and without GDM. Results: Incidence of ODIP was 1.9% of all pregnant women and 23.6% of women with 50-g GCT ≥ 200 mg/dL. Women with ODIP and GDM were more likely to be overweight or obese than those without GDM (52%, 39.6%, and 18.2%, p < 0.001). Women with ODIP had significantly higher 50-g GCT results, lower gestational weight gain, and were less likely to deliver vaginally. Insulin therapy was significantly more common in women with ODIP compared to GDM (70.2% vs. 15.4%, p < 0.001). Rates of LGA, macrosomia, and other neonatal outcomes were comparable. BMI ≥ 25 kg/m2 and 50-g GCT ≥ 240 mg/dL independently increased the risk of any abnormal glucose tolerance [adjusted OR 3.22 (95% CI 1.55-6.70) and 2.28 (95% CI 1.14-4.58)] and ODIP [adjusted OR 9.43 (95% CI 2.15-41.38) and 6.36 (95% CI 2.85-14.18)], respectively. Conclusion: Incidence of ODIP was 23.6% of women with 50-g GCT ≥ 200 mg/dL. BMI ≥ 25 kg/m2 and 50-g GCT ≥ 240 mg/dL independently increased the risk of GDM and ODIP. Neonatal complications were comparable between ODIP and those with and without GDM.

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Hepatic encephalopathy (HE) is a syndrome that is associated with both acute and chronic liver injury. It manifests as a wide spectrum of neuropsychological abnormalities, ranging from subtle impairments in executive higher functions observed in cirrhosis, through to coma in acute liver failure. In acute liver failure, the central role of ammonia in the development of brain oedema has remained undisputed for 130 years. It latterly became apparent that infection and inflammation were profound determinants for the development of severe hepatic encephalopathy, associated with the development of cerebral oedema and intracranial hypertension. The relationship of the development of hepatic encephalopathy with blood ammonia levels in cirrhosis is less clear cut and the synergistic interplay of inflammation and infection with ammonia has been identified as being fundamental in the development and progression of hepatic encephalopathy. A perturbed gut microbiome and the presence of an impaired gut epithelial barrier that facilitates translocation of bacteria and bacterial degradation products into the systemic circulation, inducing systemic inflammation and innate and adaptive immune dysfunction, has now become the focus of therapies that treat hepatic encephalopathy in cirrhosis, and may explain why the prebiotic lactulose and rifaximin are efficacious. This review summarises the current clinical perspective on the roles of inflammation and infection in hepatic encephalopathy and presents the evidence base for existing therapies and those in development in the setting of acute and chronic liver failure.

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A new scoring system termed sepsis-induced coagulopathy (SIC) has been proposed to diagnose early sepsis-induced disseminated intravascular coagulation (DIC). This study performed DIC-related analyses in patients with confirmed SIC. Data from the intensive care unit (ICU) departments of the three hospitals between 2020 and 2022 were retrospectively analyzed. Finally, 125 patients with confirmed SIC were enrolled in the study. The diagnostic value of three widely used DIC criteria was assessed in patients with newly diagnosed SIC. In addition, the diagnostic and prognostic value of antithrombin (AT) was analyzed in patients with SIC. The Japanese Association for Acute Medicine DIC criteria (JAAM) exhibited the highest DIC diagnostic rate, while the mortality risk of SIC patients demonstrated a proportional increase with higher International Society on Thrombosis and Haemostasis (ISTH) and Chinese DIC scoring system (CDSS) scores. Low AT activity (<70%) in septic patients upon SIC diagnosis predicted a very high 28-day mortality rate, almost twice as high as in the normal AT activity (≥70%) group. A decreasing tendency in AT activity after clinical interventions was correlated with increased mortality. The area under the ROC curve (AU-ROC) of AT in DIC diagnosis was statistically significant when CDSS and ISTH were used as diagnostic criteria, but not JAAM. Each of the three DIC diagnostic criteria showed diagnostic and prognostic advantages for SIC. AT could be an independent prognostic indicator for SIC but demonstrated a relatively limited DIC diagnostic value. Adding AT to the SIC scoring system may increase its prognostic power.

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BACKGROUND: Overt gastrointestinal bleeding (GIB) is a potentially serious and life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, relatively little information is available regarding overt GIB in children. OBJECTIVES: To assess the prevalence, clinical patterns, and outcomes of overt GIB in children undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: A total of 123 consecutive patients with malignant or non-malignant blood disorders who received haplo-HSCT were reviewed in our hospital between October 2017 and October 2022. Overt GIB was determined as hematemesis, melena or hematochezia. Continuous variables were compared by Mann Whitney U test. Categorical parameters were compared by the χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank tests were used to assess overall survival (OS), non-relapse mortality (NRM) and relapse. Univariate and multivariate analyses were performed to identify potential risk factors of overt GIB development. RESULTS: The median follow-up was 26.3 (range,1.7-74.8) months. Overt GIB occurred in 31 patients (25.2% incidence), with a median time elapsed after haplo-HSCT of 376 days (range, 58-1275 days). Compared with the non-GIB group, patients with overt GIB had reduced OS and increased NRM. In multivariate analysis, grade III-IV gut acute graft versus-host disease (aGvHD), thrombotic microangiopathy (TMA) and cytomegalovirus (CMV) viremia were significant risk factors for the occurrence of overt GIB after haplo-HSCT. CONCLUSIONS: Overt GIB is a frequent complication after haplo-HSCT in pediatric patients, and associated with worse survival. Grade III-IV gut aGvHD, TMA and CMV viremia were associated with its development.

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Little is known about how insecure attachment affects aggressive behavior and well-being among Vietnamese youth. Using structural equation modeling, we investigate the mediating role of subjective social status (SSS) on the paths from insecure attachment to overt aggressive behavior (OAB) and psychological well-being (PW) in a sample of 1753 Vietnamese adolescents (Mage = 16.136, SD = 0.784) and test whether the results will be replicated in another sample of 601 Vietnamese young adults (Mage = 19.93, SD = 1.35). Participants complete a survey comprising demographic information, attachment styles, SSS, OAB, and PW questionnaires. Our main findings include: (a) anxious attachment positively related to OAB in both samples, (b) anxious attachment was only negatively associated with adolescents' PW, (c) avoidant attachment was positively correlated to OAB in adolescents but negatively correlated in young adults, and (d) avoidant attachment was negatively related to PW in both samples. In addition, (e) in adolescents, the mediation role of SSS was significant in all paths, but (f) SSS only mediated the link from avoidant attachment to PW of young adults. The present study suggests that aggressive behavior might not be associated with social status or attachment in the same way in adolescents compared to young adult Vietnamese samples.

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The hobnail variant of papillary thyroid carcinoma (HVPTC) represents a distinctive and relatively rare histological subtype of thyroid malignancies. This variant is characterized by its unique cellular morphology with a hobnail appearance, that is, cells with apically positioned nuclei. There are other characteristics like micropapillary pattern and loss of cohesiveness of cells, which are indicative of HVPTC. It can be difficult to distinguish this pattern from other thyroid neoplasms; thus, a thorough microscopical examination is required. Thyroglobulin, thyroid transcription factor-1 (TTF-1), and other thyroid markers are commonly expressed by the tumor cells. Clinically, HVPTC is similar to conventional papillary thyroid cancer (PTC) in many aspects like incidence and epidemiology, but the former is associated with a worse prognosis. According to some research, the hobnail variety might behave more aggressively than conventional PTC, which highlights how crucial it is to identify and comprehend this distinct subtype. While the genetic and molecular underpinnings of HVPTC are still being elucidated, some studies have reported associations with specific genetic alterations, including BRAF, TP53, and TERT mutations. Investigating these molecular signatures may contribute to a better understanding of the variant's pathogenesis and potentially guide targeted therapeutic approaches in the future. In order to customize treatment plans, histopathology is essential in correctly diagnosing it. In this article, we present a case of PTC which presented as a solitary nodule on ultrasonogram in a 40-year-old female.

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Obscure gastrointestinal bleeding represents about 5% of all gastrointestinal haemorrhages which is characterized by continuous or recurrent bleeding from an undetermined source after an initial bidirectional endoscopy. Meckel's diverticulum is a rare but recognized cause of obscure gastrointestinal bleeding. A carefully selected line of investigations is paramount to localize the causative lesion in obscure gastrointestinal bleeding which is a challenge in subacute cases. We present a case of 35-year-old female with thalassemia minor and mild anaemia presented with acute gastrointestinal bleeding from the ectopic pancreatic mucosa of an Meckel's diverticulum where only a small focus of gastric tissue was identified histologically during the follow-up. This case discusses the rarity of this histological presentation of Meckel's diverticulum as obscure gastrointestinal bleeding and the importance of intraoperative decision-making and intraoperative enteroscopy in cases of obscure gastrointestinal bleeding when other tests are negative.

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BACKGROUNDS & AIMS: This study aimed to investigate the association between vitamin D deficiency and covert hepatic encephalopathy (CHE), overt hepatic encephalopathy (OHE) occurrence, and mortality in patients with cirrhosis. METHODS: This retrospective study reviewed 679 patients with cirrhosis. Vitamin D deficiency was defined as serum 25-hydorxyvitamin D (25-OHD) levels < 20 ng/mL. The associations between 25-OHD and CHE, OHE occurrence, and mortality were assessed using logistic regression, Fine-Gray competing risk regression, and Cox proportional hazards regression models, respectively. RESULTS: Of 428 eligible patients, 75% had vitamin D deficiency and 23% had CHE. The prevalence of CHE was higher in patients with vitamin D deficiency than in those without vitamin D deficiency (28% vs. 13%, p = 0.002). During the median follow-up period of 2.3 years, 14% of the patients developed OHE and 27% died. Patients with vitamin D deficiency had a higher incidence of OHE (p = 0.002) and mortality (p = 0.006) than those without vitamin D deficiency. After adjustment for potential covariates, multivariate analyses showed that 25-OHE was associated with CHE (odds ratio, 0.95; 95% confidence interval [CI], 0.91-0.99; p = 0.023), OHE occurrence (sub-distribution hazard ratio, 0.92; 95% CI, 0.86-0.98; p = 0.013) and mortality (hazard ratio, 0.96; 95% CI, 0.93-0.99; p = 0.020) in patients with cirrhosis. CONCLUSIONS: Vitamin D deficiency is highly prevalent and is associated with CHE, OHE, and mortality in patients with cirrhosis. Evaluation of vitamin D is essential to predict the outcomes of patients with cirrhosis.

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Hydrocephalus involves the enlargement of the ventricular system due to increased cerebrospinal fluid. This condition often presents with ventriculomegaly, associated with cognitive decline, gait disturbances, visual changes, and other neurological symptoms. In adults, hydrocephalus may result from longstanding overt ventriculomegaly in adults (LOVA), characterized by macrocephaly, subnormal IQ, urinary incontinence, and gait issues. In a recent case report, a 52-year-old Hispanic female displayed similar predisposing factors and radiological findings for a LOVA diagnosis. Despite the absence of focal neurological deficits or typical complaints, she experienced a breakthrough seizure episode after years without incident.

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Aggressive and violent behaviour is a challenging psychiatric emergency to manage, especially among vulnerable categories such as patients with Intellectual Developmental Disorder. Although there is some evidence that clozapine may be useful as an anti-violence compound, its use is limited by common metabolic complications. An adult patient presented with obesity, type II diabetes mellitus, compulsive food intake, severe Intellectual Developmental Disorder, and a treatment-resistant aggressive behaviour. Clozapine was administered resulting in reduced aggressive behaviour. Unexpectedly, a reduction in the food craving as well as a sustained improvement in both anthropometric parameters and glycemic control were observed during the clozapine treatment. Our case report, describes these findings for the first time, highlighting the need for more clinical research to investigate both the efficacy of clozapine in the Intellectual Developmental Disorder populations and its long-term effects with special regard to the metabolic outcomes in this type of patients.

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BACKGROUND: To provide patients the chance of accepting curative transjugular intrahepatic portosystemic shunt (TIPS) rather than palliative treatments for portal hypertension-related variceal bleeding and ascites, we aimed to assess hepatic-associated vascular morphological change to improve the predictive accuracy of overt hepatic encephalopathy (HE) risks. METHODS: In this multicenter study, 621 patients undergoing TIPS were subdivided into training (413 cases from 3 hospitals) and external validation datasets (208 cases from another 3 hospitals). In addition to traditional clinical factors, we assessed hepatic-associated vascular morphological changes using maximum diameter (including absolute and ratio values). Three predictive models (clinical, hepatic-associated vascular, and combined) were constructed using logistic regression. Their discrimination and calibration were compared to test the necessity of hepatic-associated vascular assessment and identify the optimal model. Furthermore, to verify the improved performance of ModelC-V, we compared it with four previous models, both in discrimination and calibration. RESULTS: The combined model outperformed the clinical and hepatic-associated vascular models (training: 0.814, 0.754, 0.727; validation: 0.781, 0.679, 0.776; p < 0.050) and had the best calibration. Compared to previous models, ModelC-V showed superior performance in discrimination. The high-, middle-, and low-risk populations displayed significantly different overt HE incidence (p < 0.001). Despite the limited ability of pre-TIPS ammonia to predict overt HE risks, the combined model displayed a satisfactory ability to predict overt HE risks, both in the low- and high-ammonia subgroups. CONCLUSION: Hepatic-associated vascular assessment improved the predictive accuracy of overt HE, ensuring curative chances by TIPS for suitable patients and providing insights for cirrhosis-related studies.

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Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health issue of social and economic relevance. Both hyperthyroidism and hypothyroidism are very common in the adult population, and both disorders may contribute to the onset and progression of CVD. After a brief description of the role of thyroid hormones (THs) on the physiology of the cardiovascular system and the potential mechanism that links THs alterations with changes in cardiac function, blood pressure, endothelial function, and lipid levels, we review updated data about the clinical impact of overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) on CV risk, CVD, and mortality. Furthermore, we summarize the current evidence for treating SCH with levothyroxine (L-T4). Several guidelines of distinguished endocrine societies recommend treatment for SCH with TSH higher than 10 mIU/L, where the benefit of L-T4 therapy is more evident for younger people, but still controversial in those aged over 65 years. Based on current knowledge, more research efforts are needed to better address the clinical management of CV risk and CVD in the elderly affected by SCH.

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OBJECTIVE: The aim of this study was to cephalometrically evaluate the pharyngeal morphology in adults with unoperated Submucous Cleft Palate (SMCP), adults with unoperated Overt Cleft Palate (OCP), and adults without clefts. DESIGN: This study employed a retrospective cross-sectional design. Lateral cephalometric radiography was performed on three groups of adults: 1) 29 with unrepaired SMCP; 2) 41 with unrepaired OCP; and 3) 39 without clefts, who served as controls. One-way ANOVA and rank-sum tests were used for intergroup comparisons. P value was set at .05. RESULTS: The soft palate length and the ratio of soft palate length to pharyngeal depth were significantly lower in subjects with unoperated SMCP and OCP than in non-cleft controls. Significant differences were also observed in pharyngeal depth, nasopharyngeal depth, and posterior pharyngeal wall thickness between subjects with unoperated OCP and non-cleft controls. CONCLUSIONS: Pharyngeal morphology differs significantly between individuals with and without clefts, particularly in soft palate length and the ratio of soft palate length to pharyngeal depth.

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Long-standing overt ventriculomegaly in adults (LOVA) is a kind of chronic hydrocephalus that has been reported to have started in infancy and is characterized by severe ventriculomegaly and macrocephaly. It often manifests clinically in later adulthood. We describe the case of a 34-year-old male patient who had a history of chronic alcoholism and who had been complaining of headaches, disturbed gait, and frequent falls for three months when he arrived in a stupor at the emergency room. Massive ventriculomegaly with Evans' index of 0.40 was found during a head magnetic resonance imaging (MRI). The MRI results were more severe than the clinical manifestations. He was diagnosed with LOVA and treated with conservative hyperosmolar drugs, neuroprotective agents, and intravenous (IV) thiamine. The patient was discharged and consented to follow-up after a hospital stay of seven days.

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Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the time-proven standards i.e., Lactulose & Rifaximin. In this RCT, we compared the efficacy of intravenous (IV) L-ornithine-L-aspartate(LOLA) versus Oral LOLA in patients with chronic liver disease(CLD) enduring overt Hepatic Encephalopathy(OHE). 40 CLD patients with OHE were randomly assigned IV or oral LOLA in a 1:1 ratio. Patients were graded for HE and monitored for serum ammonia levels from day 1 to day 5. The aim was to compare IV versus oral LOLA efficacy in HE grades improvement and its correlation with ammonia levels. The study was registered with clinical trials registry-India, CTRI/2020/12/029943. Baseline characteristics of patients in both groups were similar. The mean difference in ammonia levels from day 1 to day 5 was 55.4 ± 32.58 µmol/L in the IV LOLA group and 60.75 ± 13.82 µmol/L in the oral LOLA group (p = 0.511). Significant reductions in ammonia levels were observed from day 1 to day 5 within each group (p < 0.001). HE grade & ammonia correlated positively in both groups. LOLA, regardless of administration route, has demonstrated efficacy in OHE.

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Hypothyroidism commonly presents with dermatological and hair-related symptoms, although the loss of eyelashes and eyebrows is considered uncommon in clinical practice. Here, we present a case of milphosis secondary to uncontrolled hypothyroidism. A 24-year-old female with a history of hypothyroidism following total thyroidectomy and poor medication adherence presented with significant eyelash loss, accompanied by symptoms of dysphonia, bradyphrenia, bradylalia, constipation, pronounced fatigue, and drowsiness. Physical examination revealed periorbital edema and extensive eyelash loss affecting the upper eyelids. Laboratory analysis demonstrated a markedly elevated thyroid-stimulating hormone (TSH) level of 240.8 µIU/mL (normal range 0.38 to 5.33 µIU/L), confirming severe uncontrolled hypothyroidism. Levothyroxine treatment was reintroduced, leading to complete resolution of periorbital edema and regrowth of eyelashes after 12 weeks, coinciding with improvement in TSH levels. This clinical case adds to the limited literature on madarosis and milphosis as manifestations of hypothyroidism, emphasizing the importance of clinician awareness regarding their potential presentation in the context of the disease. Understanding these manifestations and their differential diagnoses is crucial for ensuring prompt and accurate diagnosis and treatment.

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The study aimed to investigate overt reading and naming processes in adult people with dyslexia (PDs) in shallow (transparent) language orthography. The results of adult PDs are compared with adult healthy controls HCs. Comparisons are made in three phases: pre-lexical (150-260 ms), lexical (280-700 ms), and post-lexical stage of processing (750-1000 ms) time window. Twelve PDs and HCs performed overt reading and naming tasks under EEG recording. The word reading and naming task consisted of sparse neighborhoods with closed phonemic onset (words/objects sharing the same onset). For the analysis of the mean ERP amplitude for pre-lexical, lexical, and post-lexical time window, a mixed design ANOVA was performed with the right (F4, FC2, FC6, C4, T8, CP2, CP6, P4) and left (F3, FC5, FC1, T7, C3, CP5, CP1, P7, P3) electrode sites, within-subject factors and group (PD vs. HC) as between-subject factor. Behavioral response latency results revealed significantly prolonged reading latency between HCs and PDs, while no difference was detected in naming response latency. ERP differences were found between PDs and HCs in the right hemisphere's pre-lexical time window (160-200 ms) for word reading aloud. For visual object naming aloud, ERP differences were found between PDs and HCs in the right hemisphere's post-lexical time window (900-1000 ms). The present study demonstrated different distributions of the electric field at the scalp in specific time windows between two groups in the right hemisphere in both word reading and visual object naming aloud, suggesting alternative processing strategies in adult PDs. These results indirectly support the view that adult PDs in shallow language orthography probably rely on the grapho-phonological route during overt word reading and have difficulties with phoneme and word retrieval during overt visual object naming in adulthood.