Amyloid-ß neuropathology induces bone loss in male mice by suppressing bone formation and enhancing bone resorption.

Alzheimer's disease (AD) and osteoporosis often coexist in the elderly. Although observational studies suggest an association between these two diseases, the pathophysiologic link between AD and skeletal health has been poorly defined. We examined the skeletal phenotype of 5xFAD mice, an AD model with accelerated neuron-specific amyloid-ß accumulation causing full-blown AD phenotype by the age of 8 months. Micro-computed tomography indicated significantly lower trabecular and cortical bone parameters in 8-month-old male, but not female, 5xFAD mice than sex-matched wild-type littermates. Dynamic histomorphometry revealed reduced bone formation and increased bone resorption, and quantitative RT-PCR showed elevated skeletal RANKL gene expression in 5xFAD males. These mice also had diminished body fat percentage with unaltered lean mass, as determined by dual-energy X-ray absorptiometry (DXA), and elevated Ucp1 mRNA levels in brown adipose tissue, consistent with increased sympathetic tone, which may contribute to the osteopenia observed in 5xFAD males. Nevertheless, no significant changes could be detected between male 5xFAD and wild-type littermates regarding the serum and skeletal concentrations of norepinephrine. Thus, brain-specific amyloid-ß pathology is associated with osteopenia and appears to affect both bone formation and bone resorption. Our findings shed new light on the pathophysiologic link between Alzheimer's disease and osteoporosis.

Venous thrombosis in a pseudohypoparathyroidism patient with a novel GNAS frameshift mutation and complete resolution of vascular calcifications with acetazolamide treatment.

Introduction Pseudohypoparathyroidism type IA (PHP1A) is characterized by end-organ resistance to multiple hormones and Albright's hereditary osteodystrophy (AHO). PHP1A is caused by inactivating mutations of the GNAS gene encoding the α-subunit of the stimulatory G protein (Gsα). In line with the underlying genetic defect, impaired inhibition of platelet aggregation has been demonstrated in some patients. However, no PHP1A case with thrombotic events has been described. Also, PHP1A cases typically have subcutaneous ossifications, but soft tissue calcifications are another common finding. Treatment options for those and other non-hormonal features of PHP1A are limited. Case Presentation A female patient presented with short stature, fatigue, and exercise-induced carpopedal spasms at age 117/12 years. Diagnosis of PHP1A was made based on hypocalcemia, hyperphosphatemia, elevated serum PTH, and AHO features, including short stature and brachydactyly. A novel frameshift variant was detected in the last exon of GNAS (c.1065_1068delGCGT, p.R356Tfs*47), showing complete loss of baseline and receptor-stimulated activity in transfected cells. The patient developed venous thrombosis and vascular and subcutaneous calcifications on both forearms after venous puncture on the right and extravasation of calcium gluconate during treatment on the left. The thrombosis and calcifications completely resolved following treatment with low molecular weight heparin and acetazolamide for 5 and 8 months, respectively. Conclusions This case represents the first PHP1A patient displaying thrombosis and the first successful use of acetazolamide for PHP1A-associated soft tissue calcifications, thus providing new insights into the treatment of non-endocrinological features in this disease.

Immediate complications and flow volume changes during treatment phases of bronchial thermoplasty: a single-center descriptive study.

INTRODUCTION: Bronchial thermoplasty (B.T.) is a therapeutic bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle mass. Immediate complications of B.T. include acute exacerbation of bronchial asthma, upper and lower respiratory tract infection, hemoptysis, among others. Our study assessed these immediate adverse events and the changes in forced expiratory volume in one second (FEV1%) measured four hours after each procedure from baseline. The study also aimed to examine the number of activations during each cycle of treatment and its correlation to the corresponding change in FEV1% from baseline. METHODS: A case-series analysis of 17 patients who underwent B.T. between 2014 and 2019 was done. Demographic, clinical characteristics, including pre and post-BT FEV1% measures, and the number of activations were obtained. RESULTS: Acute exacerbation of asthma was the commonest complication accounting for 33%, 57%, and 75% after BT1, BT2, and BT3, respectively. There was deterioration in FEV1% after each treatment phase, the most significant being in BT3. There was no correlation between the number of heat activations with the change in FEV1% from baseline. CONCLUSION: The number of activations in B.T. does not correlate with the immediate deterioration in FEV1%, although exacerbation of asthma is the commonest complication post-B.T.

Dabbing-Induced Hypersensitivity Pneumonitis.

Dabbing has been gaining popularity among young people in recent years due to its ability to deliver a high concentration of tetrahydrocannabinol. When produced illegally, it is usually contaminated by toxic substances and associated with multiple health hazards. We present the case of a 66-year-old woman who developed hypersensitivity pneumonitis after dabbing butane hash oil for the first time and was successfully treated with corticosteroids with complete resolution of her symptoms. This case report emphasizes the respiratory complications associated with using a noxious substance like butane hash oil and gives physicians an insight into the diagnosis and management of dabbing-induced hypersensitivity pneumonitis.

Immunohistochemical expression of non-collagenous extracellular matrix molecules involved in tertiary dentinogenesis following direct pulp capping: a systematic review.

BACKGROUND: Extracellular matrix molecules (ECMM) expression during tertiary dentinogenesis provides useful information for regenerative applications and efficacy of pulp capping materials. AIM: To identify and review the expression and roles of non-collagenous ECMM after successful direct pulp capping (DPC), following mechanical pulp exposures, via immunohistochemistry (IHC). The study addressed the question of where will successful DPC impact the IHC expression of these molecules. DATA SOURCES: In vivo animal and human original clinical studies reporting on ECMM in relation to different follow-up periods were screened and evaluated via descriptive analysis. The electronic literature search was carried out in three databases (MEDLINE/PubMed, Web of Science, Scopus), followed by manual screening of relevant journals and cross-referencing, up to December 2018. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Randomized and non-randomized controlled trials, conducted in humans and animals, were selected. Histological evidence for tertiary dentine formation was a prerequisite for IHC evaluation. STUDY APPRAISAL AND SYNTHESIS METHODS: The methodological quality of the included articles was independently assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) and the Cochrane risk of bias tool (RoB 1), respectively. RESULTS: From a total of 1534 identified studies, 18 were included. Thirteen papers evaluated animal subjects and five studies were carried out on humans. In animals and humans, fibronectin and tenascin expressions were detected in pulp and odontoblast-like cells (OLC); dentine sialoprotein was expressed in both soft and newly-formed mineralized tissue. In animals, bone sialoprotein was early expressed, in association with OLC and predentin; the immunoreactivity for dentine sialophosphoprotein and dentine matrix protein-1 was associated with the OLC and dentine bridge; osteopontin was expressed in OLC, predentine and reparative dentine. A considerable heterogeneity was found in the methodologies of the included studies, as well as interspecies variability of results in terms of time. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Within the limited scientific evidence, all non-collagenous ECMM expressions during tertiary dentinogenesis are active and related to soft and hard tissues. There is a shortage of human studies, and future research directions should focus more on them. PROSPERO Protocol: CRD42019121304.

Idiopathic Subglottic Tracheal Stenosis Misdiagnosed As Vocal Cord Dysfunction and Successfully Treated with Laser and Controlled Radial Expansion Balloon Dilation.

Idiopathic tracheal stenosis (ITS) is a rare condition, and diagnosis of exclusion should be suspected in patients with exercise intolerance, wheezing, and dyspnea on exertion with a flow-volume loop suggestive of fixed airway obstruction. We report a case of a 32-year-old asthmatic woman with an existing diagnosis of vocal cord dysfunction and previous normal CT scan of the neck. She continued to have fixed upper airway obstruction on repeated flow-volume loops with persistent wheezing and cough along with occasional stridor and hoarseness of voice despite appropriate management of her asthma. She was finally diagnosed with ITS on a repeat CT scan of the neck for which she underwent laser surgery, steroid injection, and controlled radial expansion balloon dilation with a successful reduction of stenosis. This case illustrates the importance of clinical suspicion for early diagnosis of ITS in poorly controlled asthmatic patients and the relevance of non-surgical management of this condition.

Clinical and pathological correlations in endometrial pathology.

The incidence and mortality rate of endometrial cancer has been registering an increasing trend both in Romania and in the whole world. The paper's aim is to analyze the diagnostic approach of endometrial pathology in the University Emergency Hospital Bucharest, on a four years period. The medium age of the patients was of 50.51 ± 10.924 years, and the median age was of 48 years. The youngest patient suffering from endometrial cancer was of 30 years. Dilation and uterine curettage represent the main method used in the performance of endometrial biopsy, based on which the certitude etiologic histopathologic diagnosis was established in 68.4% of the patients with endometrial pathology. Hyperplasias represented half of the pathology (54.9%), most of them being without atypias. Endometrial carcinoma was identified in 19% of the patients. The diagnosis of the disease in IA stage represents 5.5% of the total endometrial cases and the diagnosis of the disease in the stage of its limitation to the uterus (stage IA, IB and IC) was of 64.2%. The endometrioid adenocarcinoma represents the most encountered histopathological form and the degree of tumor differentiation established for 68,15% of the cases was predominantly 1 and 2 (88%). The main symptom, which determines the patients' decision to go to the physician, is the abnormal uterine bleeding. 66% of the cases of endometrial cancer in the stage of the disease limited to the uterus are diagnosed in Romania based on the abnormal uterine bleeding. However, 34% of the cases are diagnosed in advanced stages, presenting a significantly low life expectancy.

Fallopian tubes--literature review of anatomy and etiology in female infertility.

RATIONALE: Around 30% of the infertile women worldwide have associated Fallopian tubes pathology. Unfortunately, for a long time, this aspect of infertility has been neglected due to the possibility of bypassing this deadlock through IVF. OBJECTIVE: Up to date free full text literature was reviewed, meaning 4 major textbooks and around 100 articles centered on tubal infertility, in order to raise the awareness on this subject. METHODS AND RESULTS: The anatomy of the Fallopian tube is complex starting from its embryological development and continuing with its vascular supply and ciliated microstructure, that is the key to the process of egg transport to the site of fertilization. There are many strongly documented causes of tubal infertility: infections (Chlamydia Trachomatis, Gonorrhea, and genital tuberculosis), intrauterine contraceptive devices, endometriosis, and complications after abdominal surgery, etc. DISCUSSIONS: Although there are still many controversies about the etiology of tubal sterility with the advent of molecular diagnosis of infections there has been cleared the pathway of infection through endometriosis or through ciliary immobility towards the tubal obstruction.

Current management of tubal infertility: from hysterosalpingography to ultrasonography and surgery.

RATIONALE: The development of IVF techniques has diminished the importance of tubal infertility but recent discoveries shed a new light on reproductive tubal surgery prior to any IVF cycle. OBJECTIVE: To adapt current state of the art recommendations concerning tubal factor infertility to actual possibilities in Romanian healthcare system and to grow the awareness of fellow fertility specialists and general practitioners to the improved outcomes of novel management and treatment modalities. METHODS AND RESULTS: 67 free full text articles centered on the subject of management in tubal infertility were identified in international databases. Four articles described general diagnosis using data from medical history, 21 works approached the diagnosis through hysterosalpingography, 14 papers introduced the use of different sonographic procedures, 8 files analyzed the importance of exploratory laparoscopy and 20 articles reviewed different treatment modalities. DISCUSSIONS: Current data show that active implementation of the large scale use of tubal surgery prior to any IVF cycle will reduce up to 30% the costs associated with obtaining a viable pregnancy in cases with tubal factor sterility.

Biological prognostic parameters in gastric carcinomas.

Gastric cancer is the second leading cause of cancer mortality worldwide. (1) Gastric carcinogenesis involves a variety of factors including diet, habitual factors as well as environmental factors. (2,3) This study aimed to correlate clinicopathological parameters of the cases studied and PCNA and p53 expression using immunohistochemistry. The study group included a total of 32 patients that underwent gastrectomy for gastric cancer.The study parameters were represented by epidemiological aspects (age, sex), clinical characteristics (signs and symptoms),histopathological findings (pTNM staging and degree of differentiation, histological classification, lymph nodes status and presence of vascular invasion) and survival, and immunohistochemical analysis (p53 and PCNA expression) of the study group. Histopathological study showed that most of the cases(26 cases) were of the intestinal type and 6 cases of the diffuse type. Immunohistochemical analysis of p53 protein expression showed an average of 20.75% positive cells, while PCNA expression showed an average of 47.3%. In terms of survival there were 6 cases of death at intervals ranged from 2-189 days,5 cases had subsequent presentations over 12 months, while 8 patients were lost to follow-up. At the time of surgery, 6 patients had distant metastases, while 6 more developed them in a period of 2-12 months after surgery. Identification of biomolecules that highlight potentially aggressive tumors may help modulate the therapeutic approach after surgical resection.

Pseudomixoma peritonei, a rare entity difficult to diagnose and treat - case report.

The authors present the case of a 56 year-old patient diagnosed with pseudomyxoma peritonei, 4 years after being subjected to a left adnexectomy for ovarian cystadenoma. The intra-parietal insemination of the mucinous cells enabled the development,at this level, of a gelatinous mass that raised problems of differential diagnosis with irreducible incisional hernia. In what regards the preoperative signs of clinical and paraclinical diagnosis we consider them obscure and nonspecific. The abdominal computed tomography revealed the presence of a massive intraperitoneal collection, but given the rarity of this pathology the initial diagnosis was made in the course of the exploratory laparotomy. Intraoperatively it became necessary to perform the omentectomy and total hysterectomy with contralateral adnexectomy and appendectomy. The histopathological examination confirmed the diagnosis. Using cisplatin associated with aggressive surgical cytoreduction this case of pseudomixoma had a good long-term evolution. The diagnosis was a challenge, and the nonspecific slow evolution of the disease led to difficult differential diagnostic.

[Clinical and morphological features in a case of recent gastric carcinoma (the signet ring cell carcinoma type)]. / Particularitati clinico-morfologice într-un caz de carcinom gastric incipient (tipul de carcinom în inel cu pecete).

The article presents the case of a male patient, hospitalized due to severe pain in the upper abdomen area, nausea, and vomiting. The patient was diagnosed with surgical acute abdomen, for which emergency surgery is performed. Upon penetration into the peritoneal cavity, stomach inspection shows at the medio-gastric level, on the greater curvature, a callous gastric ulcer, with a central perforation. A large excision is decided up to the healthy (normal) gastric tissue, and the resulting pieces are sent to the pathological anatomy laboratory. The histopathological exam reveals signet ring cell recent gastric carcinoma. The biopsy performed 1 month after surgery, prelevated from the antropyloric zone, reveals antropyloric gastritis with moderate activity and Helicobacter pylori positive. Due to the fact that such cases when this gastric cancer type is diagnosed in recent stages are extremely rare, we considered it useful to present it and look into its macroscopic and microscopic aspects, as well as into the differentiating diagnosis.

[Surgical management of Meckel's diverticulum in adults--retrospective analyses of 62 cases]. / Atitudinea chirurgicala fata de diverticulul Meckel la adult--analiza retrospectiva a unui lot de 62 de cazuri.

Meckel's diverticulum (MD) is the most common congenital anomaly of the small intestine. We searched and analyzed the records of 62 cases with MD admitted in University Emergency Hospital Bucharest between 2001-2009. Sex ratio was M:F 3:1, with 74% male and 26% female. 51.6% (n = 32) of this where symptomatic and 48.4% (n = 30) asymptomatic, discovered during laparotomy for other reasons. The analysis highlights an increased frequency of symptomatic diverticulum at early ages, with a medium age of about 39.2 years comparing to asymptomatic group with a medium age of about 54.2 years. The diverticulum complication generated: occlusion--43.7% (n = 15), inflammation--37.5% (n = 12), bleeding, two cases of diverticulum tumor, an intussusception case and a perforation case with unknown object. 25% of the diverticulectomies were followed by postsurgery complications, the parietal suppuration being the most frequent (50%). Three patients died independent of the diverticulum or its resection, all three having an asymptomatic diverticulum. The difficult diagnosis and the seriousness of diverticulum complications force us to take into consideration DM in all cases of severe or chronic abdominal pain. The diverticulum has to be surgically removed to all patients under 50 years, especially men.

[Amyand's hernia--a clinical case]. / Hernia Amyand--caz clinic.

Amyand's hernia, a rare entity in the surgical pathology, presupposes the presence of the vermiform appendix inside a inguinal hernia sac (1). The hernia sac peritonitis by appendix swelling is even more rare, very few cases being presented in the surgical literature (1). The preoperatory diagnosis of Amyand's hernia is therefore very difficult. We herein present the case of a 71-year old male patient, operated on an emergency basis for hernia, which eventually turned out to be Amyand's hernia, a case which determined us to research the literature dedicated to this topic.

Mechanism and functional consequences of loss of FOXO1 expression in endometrioid endometrial cancer cells.

The forkhead transcription factor FOXO1, a downstream target of phosphatidylinositol-3-kinase/Akt signalling pathway, regulates cyclic differentiation and apoptosis in normal endometrium, but its role in endometrial carcinogenesis is unknown. Screening of endometrial cancer cell lines demonstrated that FOXO1 is expressed in HEC-1B cells, but not in Ishikawa cells, which in turn highly express the FOXO1 targeting E3-ubiquitin ligase Skp2. FOXO1 transcript levels were also lower in Ishikawa cells and treatment with the proteasomal inhibitor was insufficient to restore expression. Lack of FOXO1 expression in Ishikawa cells was not accounted for by differential promoter methylation or activity, but correlated with increased messenger RNA (mRNA) turnover. Comparative analysis demonstrated that HEC-1B cells proliferate slower, but are more resistant to paclitaxel-mediated cell death than Ishikawa cells, which were partially reversed upon silencing of FOXO1 in HEC-1B cells or its re-expression in Ishikawa cells. We further show that FOXO1 is required for the expression of the growth arrest- and DNA-damage-inducible gene GADD45alpha. Analysis of biopsy samples demonstrated a marked loss of FOXO1 and GADD45alpha mRNA and protein expression in endometrioid endometrial cancer compared to normal endometrium. Together, these observations suggest that loss of FOXO1 perturbs endometrial homeostasis, promotes uncontrolled cell proliferation and increases susceptibility to genotoxic insults.

[Hereditary pancreatitis]. / Pancreatita ereditara.

We present the cases of three brothers (a woman and two men) with recurrent attacks of necrotic acute pancreatitis that were treated in our clinic. Two of them have diabetes mellitus controlled through insulin treatment. All patients have presented the first episode of acute pancreatitis around age of 35. We have observed a high level of serum triglyceride at admission, without evidence of lipid disorder. In addition we couldn't identify other causes of these episodes of acute pancreatitis (biliary stones, alcohol, trauma, drugs, lipid disorders). During the last year two members of this family presented recurrent attacks of abdominal pain without any biochemical or imaging signs of acute pancreatitis.

[Gastric stromal tumors--Clinical and histopathological analysis of four cases]. / Tumori gastrice stromale--analiza clinica si histopatologica a patru cazuri.

BACKGROUND: The aim of this study is to present our experience concerning a rare form of gastric tumor--gastrointestinal stromal tumor (GIST). METHODOLOGY: We reviewed data of four patients with gastric stromal tumors, which have been admitted in our department from 1998-2002. RESULTS: There were two females and two males with age of 75, 70, 65 and 63 years old. The average duration of symptoms until hospital admission was 7 days. During surgery we discovered proximal gastric tumors with 4, 5, 10 and 20 cm in largest diameter. We performed excision of the whole tumor with a security limit of 2 cm or gastric resection (one case), without limphadenectomy. One patient developed an anastomotic fistula with a good evolution under conservative treatment. All patients left the hospital in a good condition. Histopathological and immunohistochemical study diagnosed gastric stromal tumors by identifying the CD 117 maker. Postoperatively neither one of our patients received chemotherapy or radiotherapy. One female and one male patient died of peritoneal metastasis at nine months and respectively two years after operation. The other two patients are in a good condition up to date, without metastasis, one and respectively three years after surgical treatment. CONCLUSIOUS: Correct diagnosis, complete tumor resection and surveillance are essential steps in management of gastric stromal tumors.

Evaluation of T-lymphocyte subtypes in the diagnosis of celiac disease.

The objectives of this study were to verify comparatively clinical age reported antecedents and the morphological aspect of the intestinal mucosa in patients sensitive to gluten, hospitalised at IOMC ("Alfred Russescu" Hospital) in the last 7 years. Celiac disease is an inflammation most frequently affecting the proximal small intestine, depending on the presence of gluten in the diet, whose pathogenesis seems to be immunological in nature. 107 cases were divided in three groups following clinical manifestations types at hospitalisation time: typical digestive, untypical digestive and extra digestive manifestations. Intestinal biopsies, made with Crosby probe, in children aged between 1.3 and 8 years (one single case was diagnosed as late as at the age of 15), regardless of gender. Then we analysed morphologically (HE usual and PAS histochemical staining) and immunohistochemically (lymphocytes B, T with possible subtypes). The lesions were counted at the first biopsy according to the Marsh score. The immunohistochemical tests have indicated the prevalence of T lymphocytes (UCHL1, CD3, CD4, CD8, gamma-delta) both in the luminal epithelium with various degrees of aggression in lamina propria and also spread in stroma. B-lymphocytes (L26) are distributed prevalently nodular in stroma. In conclusion, it is CD4 T cells that are present in particular in the control of the gluten immune response in patients with Marsh I and Marsh III lesions.

Histopathologic aspects in a case of strumal carcinoid (struma ovarii and carcinoid).

The authors present the histopathologic aspects in a case of strumal carcinoid (struma ovarii and carcinoid) with 5 years clinical follow-up. The differential diagnosis difficulties between a thyroid carcinoma developed within a struma ovarii and various patterns of carcinoid are also stressed.