Lipoprotein Z, a hepatotoxic lipoprotein, predicts outcome in alcohol-associated hepatitis.

BACKGROUND AND AIMS: Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation. APPROACH AND RESULTS: We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay. Serum levels of LP-Z were significantly elevated in four AH cohorts compared with control groups, including heavy drinkers and patients with cirrhosis. We defined a Z-index, calculated by the ratio of LP-Z to total apolipoprotein B-containing lipoproteins, representing the degree of deviation from normal VLDL metabolism. A high Z-index was associated with 90-day mortality independent from the Model for End-Stage Liver Disease (MELD) and provided added prognosticative value. Both a Z-index ≤ 0.6 and a decline of Z-index by ≥0.1 in 2 weeks predicted 90-day survival. RNA-sequencing analyses of liver tissues demonstrated an inverse association in the expression of enzymes responsible for the extrahepatic conversion of VLDL to LDL and AH disease severity, which was further confirmed by the measurement of serum enzyme activity. To evaluate whether the FC in LP-Z could contribute to the pathogenesis of AH, we found significantly altered FC levels in liver explant of patients with AH. Furthermore, FC in reconstituted LP-Z particles caused direct toxicity to human hepatocytes in a concentration-dependent manner, supporting a pathogenic role of FC in LP-Z. CONCLUSIONS: Impaired lipoprotein metabolism in AH leads to the accumulation of LP-Z in the circulation, which is hepatotoxic from excessive FC. A Z-index ≤ 0.6 predicts 90-day survival independent from conventional biomarkers for disease prognostication.

Can CK-MB be used as a marker in benign paroxysmal positional vertigo attack?

OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) is one of the main causes of vertigo. More than 90% of cases of positional vertigo and nystagmus can be associated with BPPV. There is no known specific laboratory test for BPPV. Because of the possible muscle activity in BPPV (especially result of nause, vomiting and increasing heart rate) we thought the CK-MB levels may change in this situation. The purpose of this study was to investigate the relation between serum CK-MB levels and BPPV and attacks. MATERIALS AND METHODS: The medical records of 35 patients with BPPV presenting to our clinic between November 2014 and November 2015 were investigated retrospectively. Thirty-two control patients with no vertigo, muscular or cardiac disease and with measured CK-MB levels were randomized into a control group. Both groups' existing CK-MB levels were obtained from the patient records. CK-MB values measured before BPPV attack from 11 patients in the patient group were also recorded. RESULTS: The patient and control groups were similar in terms of demographic parameters. CK-MB values at time of attack in the patient group ranged between 5.4 and 38.9 (mean: 19.67 ± 6.81), while control group values ranged between 12 and 27.9 (mean: 20.31 ± 4.54). CK-MB values in 11 patients in the patient group measured before attack ranged between 8.9 and 24 (mean: 17.02 ± 4.97), and CK-MB values during attack ranged between 9 and 34 (mean: 19.74 ± 7.64). CONCLUSION: Although CK-MB elevation at time of attack was determined in patients with BPPV, this was not statistically significant.

Unmasking the Enigma of Weil's Disease: A Case Report.

We present the case of a 37-year-old male with Weil's disease, a severe form of leptospirosis, who presented without typical ecological risk factors. Initially manifesting as weakness, muscle aches, and fever, the patient rapidly deteriorated, necessitating ICU admission due to septic shock and respiratory failure. Despite initial diagnostic challenges, including normal initial imaging and inconclusive laboratory findings, a presumptive diagnosis of leptospirosis was made using Modified Faine's criteria. Empirical antibiotic treatment with doxycycline led to significant clinical improvement, highlighting the importance of early recognition and treatment in severe cases of leptospirosis. This case underscores the need for heightened clinical suspicion and the use of diagnostic scoring systems, even in atypical presentations, to facilitate timely intervention and improve patient outcomes.

Unveiling the Chilaiditi Syndrome: A Case Report and Management Implications.

The Chilaiditi syndrome is when the radiologic Chilaiditi sign, defined by the interpositioning of the colon between the liver and diaphragm, becomes complicated by clinical symptoms such as respiratory insufficiency or bowel obstruction. We present the case of a 70-year-old male with a history of depression, anxiety, gastroesophageal reflux disease (GERD), and post-polio syndrome, who presented with left shoulder pain, chronic weakness, and dizziness. Initial evaluation revealed hypotension and elevated lactic acid, attributed to dehydration. Further imaging identified a Chilaiditi sign, thus raising suspicion of small bowel obstruction and the Chilaiditi syndrome. Despite conservative management, the patient continued to experience elevated lactic acid levels, prompting a computed tomography (CT) angiogram to rule out bowel ischemia. No acute intra-abdominal pathology was identified, and the patient improved with hydration and bowel rest. This case highlights the challenges in diagnosing and managing the Chilaiditi syndrome in the setting of chronic comorbidities.

[Anatomical and functional results of open cavity tympanomastoidectomy]. / Açik kavite timpanomastoidektominin anatomik ve fonksiyonel sonuçlari

OBJECTIVES: In this study, we aimed to evaluate the anatomical and functional results of open cavity tympanomastoidectomy due to chronic otitis media with cholesteatoma. PATIENTS AND METHODS: Between January 2003 and October 2009, 166 patients who underwent open cavity tympanomastoidectomy due to chronic otitis media with cholesteatoma in our clinic were retrospectively analyzed. Seventy-two ears of 69 patients (40 males, 29 females; mean age 36.7±17.7 years; range 9 to 64 years) who visited on a regular basis due to acquired middle ear cholesteatoma were included. Cholesteatoma was classified as attic, sinus and tensa retraction cholesteatoma, according to its localization. Audiological findings were compared based on the localization of cholesteatoma and intraoperative ossicular status. RESULTS: The mean follow-up was 36.3±27.0 months (range 6 to 88 months). There were six (8.4%) greft failures, four (5.6%) graft retractions, and one (1.4%) recurrent cholesteatomas in the ears of the patients. There were also five (7%) pearly residual cholesteatomas. At the last visit following surgery, 97.2% of cavities were dry and self-cleaning. The mean preoperative pure tone air threshold was 53.5±22 dB, while it reduced to 52.2±23.3 dB at the last visit in 48 ears operated open cavity tympanomastoidectomy type 1, 2, 3, and 4 in combination with hearing reconstruction (p=0.454). There was a statistically significant reduction in the mean air-bone gap of the attic cholesteatomas, decreasing from 27.2±14.6 dB to 21.6±12.2 dB (p=0.007). Air-bone gap values were lower than 20 dB in 23 (47.9%) of the cases and the gain was more than 10 dB in 17 (35.5%). No statistically significant correlation was found between the localization of cholesteatoma and intraoperative ossicular status (p>0.05). CONCLUSION: Open cavity tympanomastoidectomy, which allows total removal of the pathology, is an applicable surgical approach with satisfactory outcomes for hearing reconstruction.

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

[Evaluation of operation success in patients with nasal septal deviation with quality of life scale and objective methods]. / Nazal septum deviyasyonlu hastalarda ameliyat basarisinin yasam kalitesi ölçegi ve objektif yöntemler ile degerlendirilmesi.

OBJECTIVES: In this study we aimed to evaluate the quality of life during, before and after septoplasty in patients who were diagnosed with nasal septal deviation and also to demonstrate the role and importance of acoustic rhinometry and rhinomanometry methods in objectively demonstrating surgical success. PATIENTS AND METHODS: This study was carried out in 44 patients undergoing septoplasty surgery. Patients' preoperative complaints were evaluated by Nasal Obstruction Symptom Evaluation (NOSE) scale. The pre- and post-decongestion acoustic rhinometry and rhinomanometry data of the patients were recorded simultaneously. One month after Cottle's septoplasty performed as the septal surgery method, patients were re-evaluated by NOSE scale, acoustic rhinometry and rhinomanometry and the findings were compared with the preoperative data. RESULTS: Compared to the patients' preoperative values, a significant decrease in NOSE scores (p<0.05); a significant increase in the minimal cross-sectional area (MCA1, MCA2) and volume values measured by acoustic rhinometry (p<0.05) and a significant decrease in the nasal resistance values measured by rhinomanometry (p<0.05) were observed. No significant relationship was found between the change in patients' pre- and postoperative NOSE score values and the change in their acoustic rhinometry and rhinomanometry data (p>005). CONCLUSION: Nowadays, evidence-based medical practices are increasingly gaining importance and acoustic rhinometry and rhinomanometry are methods that can be used in objective evaluation of operation success.

[Incidental thyroid carcinoma found during surgery for laryngeal carcinoma: a case report]. / Larenks karsinomu nedeniyle boyun diseksiyonu yapilan olgularda rastlantisal tiroid karsinomu: Olgu sunumu.

At the histopathologic examination of neck dissection specimens of the patients who underwent surgical treatment with the diagnosis of laryngeal cancer, thyroid cancer metastases may also be detected in addition to laryngeal cancer metastases. Were retrospectively reviewed the files of 74 patients who were diagnosed with laryngeal cancer and underwent total or partial laryngectomy and neck dissection in our clinic between January 2008 and July 2010. Thyroid papillary carcinoma was found in neck dissection specimen of two patients who underwent partial laryngectomy and neck dissection. Total thyroidectomy was performed to complete the treatment. No recurrence or metastasis was found during the postoperative follow-up for an average of 9.5 months (range 5 to 14 months). Although it is a rare condition, the possibility of coexisting thyroid carcinoma in laryngeal cancer patients and the possible need for completion surgery when required should always be kept in mind.

Adenosine deaminase 2 produced by infiltrative monocytes promotes liver fibrosis in nonalcoholic fatty liver disease.

Elevated circulating activity of adenosine deaminase 2 (ADA2) is associated with liver fibrosis in nonalcoholic fatty liver disease (NAFLD). In the liver of NAFLD patients, ADA2-positive portal macrophages are significantly associated with the degree of liver fibrosis. These liver macrophages are CD14- and CD16-positive and co-express chemokine receptors CCR2, CCR5, and CXCR3, indicating infiltrative monocyte origin. Human circulatory monocytes release ADA2 upon macrophage differentiation in vitro. When stimulated by recombinant human ADA2 (rhADA2), human monocyte-derived macrophages demonstrate upregulation of pro-inflammatory and pro-fibrotic genes, including PDGF-B, a key pro-fibrotic cytokine. This PDGF-B upregulation is reproduced by inosine, the enzymatic product of ADA2, but not adenosine, and is abolished by E359N, a loss-of-function mutation in ADA2. Finally, rhADA2 also stimulates PDGF-B production from Kupffer cells in primary human liver spheroids. Together, these data suggest that infiltrative monocytes promote fibrogenesis in NAFLD via ADA2-mediated autocrine/paracrine signaling culminating in enhanced PDGF-B production.

Global deletion of NTPDase3 protects against diet-induced obesity by increasing basal energy metabolism.

BACKGROUND: Ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3), also known as CD39L3, is the dominant ectonucleotidase expressed by beta cells in the islet of Langerhans and on nerves. NTPDase3 catalyzes the conversion of extracellular ATP and ADP to AMP and modulates purinergic signaling. Previous studies have shown that NTPDase3 decreases insulin release from beta-cells in vitro. This study aims to determine the impact of NTPDase3 in diet-induced obesity (DIO) and metabolism in vivo. METHODS: We developed global NTPDase3 deficient (Entpd3-/-) and islet beta-cell-specific NTPDase-3 deficient mice (Entpd3flox/flox,InsCre) using Ins1-Cre targeted gene editing to compare metabolic phenotypes with wildtype (WT) mice on a high-fat diet (HFD). RESULTS: Entpd3-/- mice exhibited similar growth rates compared to WT on chow diet. When fed HFD, Entpd3-/- mice demonstrated significant resistance to DIO. Entpd3-/- mice consumed more calories daily and exhibited less fecal calorie loss. Although Entpd3-/- mice had no increases in locomotor activity, the mice exhibited a significant increase in basal metabolic rate when on the HFD. This beneficial phenotype was associated with improved glucose tolerance, but not higher insulin secretion. In fact, Entpd3flox/flox,InsCre mice demonstrated similar metabolic phenotypes and insulin secretion compared to matched controls, suggesting that the expression of NTPDase3 in beta-cells was not the primary protective factor. Instead, we observed a higher expression of uncoupling protein 1 (UCP-1) in brown adipose tissue and an augmented browning in inguinal white adipose tissue with upregulation of UCP-1 and related genes involved in thermogenesis in Entpd3-/- mice. CONCLUSIONS: Global NTPDase3 deletion in mice is associated with resistance to DIO and obesity-associated glucose intolerance. This outcome is not driven by the expression of NTPDase3 in pancreatic beta-cells, but rather likely mediated through metabolic changes in adipocytes.

The importance of calprotectin levels in obstructive sleep apnea syndrome severity.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is mostly seen in adult populations. It is known that increased levels of several inflammatory mediators play roles in OSAS and related comorbidities. Calprotectin is an inflammatory mediator that increases in some diseases such as Behçet's syndrome, bowel diseases and cardiovascular and cerebrovascular diseases. AIMS: The purpose of this study was to investigate whether calprotectin can be used as a biomarker in OSAS by determining the relation between serum calprotectin levels and OSAS severity. STUDY DESIGN: Cohort study. METHODS: A prospective study was planned. Eighty-three patients undergoing polysomnography were included in the study and evaluated prospectively. Thirty patients were classified as non-OSAS (group 1), 18 as mild OSAS (group 2), 15 as moderate OSAS (group 3) and 20 as severe OSAS (group 4). Calprotectin values were measured in the non-OSAS patients (group 1) and in the patients with OSAS (groups 2, 3 and 4). The OSAS groups were also compared with each other. RESULTS: Serum calprotectin values ranged between 70.61 and 1468.04 ng/ml. No significant difference in calprotectin levels was found between the OSAS and normal groups. However, statistically significantly increased calprotectin values were determined in the severe OSAS group (group 4) when all groups were compared. CONCLUSION: Calprotectin values were elevated in OSAS patients and it can be used as a marker of severe OSAS. Future studies can support our study.