Unexplained Elevation Research Articles

Malignant Hyperthermia: A Life-Threatening Condition in Patients Undergoing Surgical Intervention

Malignant hyperthermia (MH) is a rare, potentially fatal genetic disorder characterized by an unexplained elevation of expired carbon dioxide despite increased minute ventilation, muscle rigidity, and rhabdomyolysis, hyperthermia, tachycardia, acidosis, and hyperkalemia. It can be triggered by many pharmacological agents such as potent inhalation agents (halothane/ isoflurane/ sevoflurane/ desflurane), the depolarizing muscle relaxant (succinylcholine), and extreme physiological conditions such as vigorous exercise and working excessively in a hot and dry environment. Prompt and early recognition of the condition and rapid initiation of treatment measures are necessary to salvage the patient. Since MH is commonly encountered in the operating room or early postoperative period, anesthetists and surgeons need to keep themselves updated regarding the same. This review article aims to summarize our understanding of MH's pathophysiology, current diagnostics, management, and treatment strategies, along with a brief review of literature of published cases in Indian Subcontinent.

Feasibility of mNGS in joint replacement patients exhibiting elevated ESR and CRP levels without an underlying diagnosis

ObjectiveThe aim of this study is to investigate the viability of performing initial artificial joint replacement surgery in patients presenting with unexplained elevations in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels.MethodsA cohort of 22 patients, comprising 11 cases each for knee and hip joint replacements, who underwent initial artificial joint replacement surgery between November 2020 and January 2022, was recruited. All patients exhibited elevated levels of ESR and CRP prior to surgery, the etiology of which remained undetermined. Intraoperatively, joint effusion and periarticular tissues were preserved for subsequent bacterial culture and metagenomic next-generation sequencing (mNGS). Postoperatively, a combination of intravenous and local antibiotics was administered for anti-infective management. In cases where bacterial culture and/or mNGS yielded positive results, patients were diagnosed with periprosthetic joint infections (PJI) and underwent one-stage revision; conversely, negative findings led to the discontinuation of intravenous and local antibiotics therapy.ResultsAmong the cohort of 22 patients, bacterial cultures yielded negative results, while mNGS identified bacterial infection in 14 patients (63.63%), viral infection in 1 patient (4.55%), and yielded negative results in 7 patients (31.82%). All surgical incisions achieved per primam. Subsequent follow-up assessments conducted for more than 1 year postoperatively revealed absence of PJI among the patients, all of whom exhibited satisfactory progress in their rehabilitation exercises. Notably, the Knee Society Score (KSS) for knee joint patients significantly improved from a preoperative mean of 48.7 ± 3.3 points to 84.3 ± 2.2 points postoperatively, whereas the Harris Hip Score for hip joint patients increased significantly from preoperative mean of 50.6 ± 3.6 points to 87.1 ± 1.6 points (P < 0.01).ConclusionIn cases where patients present with unexplained elevations in ESR and CRP levels, primary artificial joint replacement can be undertaken following a one-stage revision approach for PJI.

Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder

BACKGROUND AND AIMPorto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension (PH). Liver biopsy (LB) is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyl transferase (GGT). This multicenter study aims to establish PSVD prevalence in a larger dataset of individuals with persistent and unexplained GGT elevation, and to identify associated risk factors. METHODSThe study included all patients who underwent LB for persistent and unexplained GGT elevation in five Italian Hepatology Units between March 2015 and December 2021. RESULTS144 patients met the inclusion criteria. The majority were males (76/144, 52.8%) and mean age was 51.9 years (range 19-74). Only twelve (8.3%) had liver stiffness measurements (LSM) >10 kPa, 7 (4.8%) had ultrasound PH evidence. Histological findings were consistent with PSVD in 96 patients (67%). Alternative diagnoses were steatohepatitis in 13 (9%), sarcoidosis in 3 (2%) and congenital hepatic fibrosis in 3 (2%). Histological findings were non-specific in 29 (20%) patients. PSVD was associated with male sex (odds ratio, OR = 2.60, 95% confidence interval, CI: 1.13-5.99), LSM < 10 kPa (OR = 11.05, 95% CI: 2.16-56.66) and GGT < 200 U/L (OR = 2.69, 95% CI: 1.22-5.98). CONCLUSIONSPSVD was the main cause of persistent and unexplained elevation of GGT. Male sex, LSM < 10kPa and GGT < 200U/l were associated with PSVD. These findings highlight the role of LB in elucidating the underlying pathology and aiding in the diagnosis of patients with persistent and unexplained GGT elevation. IMPACT AND IMPLICATIONSIn outpatient settings, it is common to encounter subjects with persistent and unexplained GGT elevation. This study reveals, for the first time, a non-negligible prevalence of porto-sinusoidal vascular disorder (PSVD) among these subjects when they undergo liver biopsy. Male sex, liver stiffness measurement (LSM) < 10 kPa, and GGT < 200 IU/L predict this histological finding.These results may raise awareness of clinically relevant conditions that may be present in patients with persistent liver enzyme changes, even in the absence of signs of advanced chronic liver disease or portal hypertension (PH). Additionally, the data may encourage further studies in the field of PSVD, particularly to define its clinical evolution in patients without signs of PH at diagnosis.

WED-130 Prevalence and predictors of porto-sinusoidal vascular disorder in patients with persistent and unexplained gamma-glutamyl transferase elevation: a multicenter study

WED-130 Prevalence and predictors of porto-sinusoidal vascular disorder in patients with persistent and unexplained gamma-glutamyl transferase elevation: a multicenter study

Dual-tracer PET/CT in the management of hepatocellular carcinoma

Background & AimsCombined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron emission tomography-computed tomography (PET-CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. MethodsWe retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET-CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET-CT in diagnosing HCC were evaluated. A Multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. ResultsDual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with an estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n=273, κ=0.822; 95% CI 0.803-0.864). ConclusionsDual-tracer PET/CT provides additional value to conventional imaging in HCC patients by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.• Impact and implications• Dual-tracer PET-CT detected 12% more disease in HCC patients undergoing staging than CT or MRI, resulting in change in treatment in 8% of cases and a cost saving of US$495 per patient.• It is also able to accurately detect HCC in high-risk cases where CT or MRI are equivocal or normal.• Dual-tracer PET/CT provides additional value to conventional imaging in HCC patients by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

A rare case of exophytic pancreatic ductal adenocarcinoma with multiple metastases shown on 18F-FDG PET/CT

Exophytic pancreatic cancer is an extremely rare subtype of pancreatic cancer that has not been strictly defined but is based on morphological origin. Herein, we reported a 69-year-old man who presented with an unexplained elevation of CA199. He was diagnosed with exophytic pancreatic cancer by β-2-Fluoro-2-deoxy-D-Glucose (18F-FDG) Positron Emission Tomography (PET)/Computed Tomography (CT), which exhibited a high 18F-FDG-avid mass behind the body of the pancreas. In addition, multiple metastases, including liver, lung, and lymph nodes, were apparently detected. Finally, Pancreatic Ductal Adenocarcinoma (PDAC) was pathologically confirmed. A posterior pancreatic mass attached to the pancreas and accompanied by elevated CA199 and hyperglucose metabolism could be linked to exophytic pancreatic cancer, which is significant to be aware of for early diagnoses and treatment.

Syphilitic hepatitis.

Syphilis is a sexually transmitted multisystemic disease known as "the great imitator" due to its variable presentations. Despite being preventable and curable, it still constitutes a major health problem. Hepatic manifestation of syphilis is usually mild cholestatic liver injury but in very rare cases can become fulminant. Moreover, syphilitic hepatitis, known for several decades, is considered rare but is probably under-diagnosed. Given the significant morbidity associated with a missed diagnosis, syphilitic hepatitis should be taken into account as an element of differential diagnosis in patients with unexplained elevation of liver enzymes.

Case Report: Acute cerebral infarction as the initial manifestation of malignant tumors with trousseau syndrome in the elderly

Both acute cerebral infarction and malignant tumors are prevalent in the elderly. However, acute cerebral infarction is rarely present as the first clinical manifestation of malignant tumors. By searching the Picture Archiving and Communication System from 2010 to 2022 and the medical record database from 2003 to 2022, we found three cases of Trousseau syndrome, one male and two females with an average age of 69.3 ± 3.2 years, presenting with acute cerebral infarction. Two patients denied having hypertension, diabetes, and coronary heart disease. The average value of the D-dimer was 17.83 ± 12.39 mg/L (normal range, 0 to 0.55 mg/L). Magnetic resonance imaging (MRI) of the brain showed scattered and multiple small infarcts in the watershed area. The sites of infarction were not those that are typically caused by vascular atherosclerosis. One of the females was diagnosed with pancreatic cancer (T2N2M1, stage IV), the male was diagnosed with gastric cancer (T4N3M1, stage IV), and the other female was diagnosed with lung adenocarcinoma (rTxN3M1b, stage IV). The patient with pancreatic cancer underwent a comprehensive geriatric assessment, which revealed that she had a disability, dementia, malnutrition, short life expectancy, and high chemotherapy risk. Ultimately, the patient opted for conservative care, and 3 months after being discharged, she passed away from an acute upper gastrointestinal hemorrhage. Elderly patients with unexplained D-dimer elevation, multiple cerebral vascular lesions detected on MRI, and an absence of typical stroke risk factors need to be monitored for Trousseau syndrome. To screen for cancer, tumor markers and related imaging should be performed first. Trousseau syndrome is primarily treated with chemotherapy, radiotherapy and anticoagulant therapy. The risk of bleeding should be assessed carefully when using anticoagulant therapy in the elderly. Comprehensive geriatric assessment can assist in weighing the benefits and side effects of cancer treatment, making correct medical choices, and improving patients’ quality of life.

Case report: Takotsubo syndrome following percutaneous coronary intervention

BackgroundTakotsubo syndrome (TTS), which is frequently secondary to severe emotional (fear, anxiety, etc.) or physical stress, is an acute reversible heart failure syndrome characterized by temporary left ventricular regional systolic dysfunction. Nevertheless, TTS after percutaneous coronary intervention (PCI) is rare, and its clinical characteristics are easily confused with complications after PCI.Case presentationThis article reports a case of TTS induced by psychological and physical pressure after successful PCI in our institution. The patient had symptoms comparable to complications after PCI, including V1-V5 ST segment elevation and T wave changes of electrocardiogram (ECG) and troponin elevation. Coronary angiogram, left ventricle opacification (LVO), and cardiac magnetic resonance (CMR) were performed to exclude postoperative complications. Diagnosis of TTS was eventually achieved.ConclusionWe cannot dismiss the risk of TTS in patients who have unexplained V1-V5 ST segment elevation and T wave changes of ECG and troponin elevation following successful PCI. Meanwhile, medical personnel should provide mental, cultural, and emotional services to patients in addition to essential diagnostic and treatment technical services during the perioperative period.

Unexplained increases in serum carcinoembryonic antigen levels in colorectal cancer patients during the postoperative follow-up period: an analysis of its incidence and longitudinal pattern

Background Carcinoembryonic antigen (CEA) monitoring facilitates the detection of recurrence in patients with colorectal cancer (CRC) after resection. False-positive CEA has been reported in CRC patients with certain comorbidities or smokers. However, limited information is currently available on the frequency of and changes in falsely elevated CEA levels in patients without these conditions. Materials and methods We retrospectively examined CRC patients who underwent surgical resection at our hospital between 2001 and 2017, had no recurrence for at least five years, and were free of known factors that may increase CEA. Postoperative CEA levels were retrieved until 2 years before the last contact. For comparison, we similarly selected patients who developed recurrence after resection of CRC during the same period, and CEA levels at initial presentation, at nadir, and at the time of recurrence were reviewed. The patterns of elevated CEA (>5 ng/ml) were classified as transient, repeated, or persistent based on longitudinal changes. The relationships between CEA and carbohydrate antigen 19-9, transaminases, creatinine, and C-reactive protein were examined. Results CEA elevation occurred in 90 (20%) out of 446 eligible patients without recurrence at least once during the mean postoperative period of 50.5 months, whereas CEA was >5 ng/ml in 117 (53%) of 221 patients when they developed recurrence. Twenty-seven patients without recurrence showed a transient elevation in CEA, 45 repeated elevations, and 18 a persistent elevation; the frequency of a high preoperative CEA level increased in this order. The majority (98%) of false elevations ranged between 5 and 15 ng/ml. CEA was not associated with other laboratory data. Conclusions Unexplained CEA elevations were observed in 20% of recurrence-free CRC patients after surgery, and were classified into three patterns based on longitudinal changes. A more detailed understanding of patient-specific fluctuations in CEA will prevent unnecessary imaging studies and reduce medical costs.

Serpin-PC in Persons with Severe Hemophilia (PwH): Updated Results from a Multicenter Multi-Part, First-in-Human Study

Introduction SerpinPC is an investigational serine protease inhibitor (SERPIN) engineered to specifically inhibit Activated Protein C (APC). The previously presented data from the completed parts of AP-0101 showed that administration of SerpinPC reduced bleeding in persons with severe hemophilia with no observations of unexplained chronic elevation in D-dimer. We will now present all results up to the end of Part 5 by which time we anticipate the median continuous exposure will be more than 3 years. Methods AP-0101 is an ongoing first-in-human open-label multicenter study utilizing an adaptive design to investigate the safety, tolerability, pharmacokinetics and efficacy of SerpinPC in subjects with severe hemophilia A and B. Part 1a was a Single Ascending Dose Study of SerpinPC in 15 healthy male volunteers and 12 males with severe hemophilia. Part 2 enrolled 23 males with severe hemophilia (19 hemophilia A and 4 hemophilia B), who were not on replacement factor prophylaxis, to receive SerpinPC at 0.3, 0.6 or 1.2 mg/kg, administered as a subcutaneous (SC) injection once every 4 weeks over a 24-week period (6 total doses). In Part 3, subjects who completed Part 2 received a flat dose of 60 mg of SerpinPC once every 4 weeks for 48 weeks. Part 4 was a further extension in which subjects who completed Part 3 received 1.2 mg/kg of SerpinPC once every 2 weeks for 24 weeks. Part 5 was a further extension in which subjects who completed Part 4 continued to receive 1.2 mg/kg of SerpinPC once every 2 weeks for 52 weeks. Results Annualized bleed rates, safety and tolerability for Part 5 will be available and a complete summary of all results to the end of Part 5 will be presented, including available pharmacokinetic and anti-drug antibody data.

A 68-Year-Old Woman With Unexplained Liver Enzyme Elevation and Active Chronic Hepatitis: Beware of Drug-Induced Autoimmune-Like Hepatitis

A 68-Year-Old Woman With Unexplained Liver Enzyme Elevation and Active Chronic Hepatitis: Beware of Drug-Induced Autoimmune-Like Hepatitis

Wilson – Konovalov Disease: Clinical Cases with Different Manifestations and Outcomes

Аim: to describe clinical cases of Wilson – Konovalov disease in pediatric patients.Key points. The first clinical case demonstrates the manifestation of Wilson – Konovalov disease with unexplained mild elevation of aminotransferases at the age of 6 years. Despite the persistent hyperenzymemia, no additional laboratory tests were prescribed. At the age of 10, the patient showed signs of liver failure and neurological symptoms. Laboratory and instrumental examination enabled to diagnose Wilson – Konovalov disease at the stage of liver cirrhosis. The diagnosis was confirmed at the Federal medical center. The diagnosis was delayed and made 4 years after the hyperenzymemia was first revealed. The relief of clinical signs was observed after the orthotopic transplantation of the right lobe of the liver from a living related donor. The patient was under surveillance for 10 years after the transplantation.The second clinical case shows another variant of the course of the Wilson – Konovalov disease manifested as an acute hepatitis. To clarify the etiology of the disease, the patient was hospitalized. In 2 weeks, the patient developed symptoms of acute liver failure, progressive hemorrhagic syndrome, acute hepatic encephalopathy. Death from fulminant hepatitis occurred in 3 weeks after the disease onset after the disease onset.Conclusion. Healthcare workers should be aware of clinical signs of Wilson – Konovalov disease. Screening for the disease is recommended for children with an unexplained increase of liver transaminases, acute liver failure, chronic hepatitis and liver cirrhosis.

A Cross-Sectional Study on Histological Pattern of Primary Glomerular Diseases among Adult Patients

Background and Aims: Primary glomerulonephritis (GN) is the major cause for end-stage renal disease (ESRD) and considered to contribute in 52% cases. Kidney biopsy is an essential tool in nephrologists' clinical practice for determining diagnosis, prognosis, and therapy of a variety of glomerular conditions. The purpose of the present study was to determine the primary glomerular diseases histopathological pattern among adult patients. Patients and Methods: A total of 94 suspected primary glomerular disease (GD) patients were investigated in this cross-sectional study conducted in the Nephrology Unit of Medicine department of Mayo Hospital, Lahore from 21st January 2021 to 20th February 2022. Individual’s demographic details, diagnostic tests, clinical presentation, kidney biopsy indications, and post-biopsy complications were recorded on pre-designed questionnaire/pro-forma. Data analysis was done using SPSS version 27. Results: Out of 94 patients, about 76 (80.9%) patients had primary glomerular disease diagnosed on native kidney biopsies. The overall mean age was 38.4± 6.2 years. Out of 94 primary glomerular disease patients, there were 48 (51.1%) male and 46 (48.9%) females. The incidence of nephrotic syndrome and unexplained renal parameters elevations were 47.4% (n=36) and 31.6% (n=24) respectively. The prevalence of Primary focal segmental glomerulosclerosis (FSGS), membrano-proliferative glomerulonephritis (MPGN), minimal change disease, and IgA nephropathy was 30.3% (n=23), 25% (n=19), 17.1% (n=13), and 6.6% (n=5) respectively. Kidney biopsy post-complications were found in 8 (10.5%) cases. Conclusion: The present study observed that MPGN and FSDS were the most prime causes for primary glomerular disease. The most prevalent indication of kidney biopsy was nephrotic syndrome. Keywords: Glomerular disease, kidney biopsy, histopathological pattern, adult patients

Can Bone-Specific Alkaline Phosphatase be a Marker of Vascular Calcification in Type 2 Diabetes Mellitus?

Alkaline phosphatase (ALP) enzyme has been linked to vascular calcification. Unexplained elevations in serum ALP levels have been reported in patients with type 2 diabetes mellitus (T2DM). We assessed bone-specific alkaline phosphatase (BAP) levels in patients with T2DM who had unexplained ALP elevations and studied the association between BAP and other markers of vascular calcification. Patients with T2DM who had high serum ALP in the absence of known causes of ALP elevation were studied. The control group was T2DM patients with normal ALP. We measured the serum levels of BAP along with the leptin, fetuin-A, and vitamin K2 levels. Ankle-brachial index (ABI) was also measured in both groups. Serum BAP levels were significantly higher in the group with high ALP when compared with the normal ALP group. A significant positive correlation was present between BAP and serum fetuin-A as well as between BAP and Vit K2 levels. There was no correlation between BAP and serum leptin. ABI was comparable between the two groups. Patients with T2DM may have unexplained elevation in ALP due to an increase in BAP. Elevation in BAP may be associated with other markers of vascular calcification suggesting an increased risk of vascular calcification.

PSAT223 A Delayed Diagnosis of Oncogenic Osteomalacia Presenting with Bone Pain, Muscle Weakness and Elevated Alkaline Phosphatase

Abstract Background Tumor-induced osteomalacia (TIO) is a rare bone disease caused by excess production of FGF23 by a phosphaturic mesenchymal tumor, resulting in severe hypophosphatemia, bone demineralization, insufficiency fractures, bone pain and muscle weakness. The Fibroblast Growth Factor-23 (FGF23) is a phosphaturic hormone produced by osteocytes, whose primary effect is to decrease serum phosphate by suppressing proximal tubular phosphate reabsorption and intestinal phosphate absorption (via diminished 1,25D production). Clinical case A 65-year-old male was referred to endocrinology clinic for a second opinion due to severe rib pain and elevated alkaline phosphatase levels. His first endocrinologist diagnosed Paget's disease of the bone based on symptoms of rib pain, an elevated alkaline phosphatase level, and abnormal Tc99 bone scintigraphy demonstrating uptake in multiple areas, including bilateral humeri, ribs, knees, ankles, and L4 vertebral body. He received 5 mg IV zoledronate for treatment of Paget's disease, and immediately post-infusion reported worsening of severe rib pain. Upon presentation to our institution, he reported ongoing severe rib pain and bilateral knee pain. On exam, he had extreme difficulty rising from a seated position. Laboratories revealed calcium 9.0 mg/dL, albumin 5.0 g/dL, alkaline phosphatase 116 U/L, 25D 43 ng/dL, PTH 66 pg/mL and serum phosphorous 1.5 mg/dL. Tubular Reabsorption of Phosphate (TRP) was 59%, based on a spot second morning void with corresponding fasting morning blood draw. 1,25D was 13 pg/mL (19-79 pg/mL). Intact FGF23 was 346 pg/mL (&amp;lt;59 pg/nL). CT revealed bilateral tibial plateau insufficiency fractures. When asked if he noticed any "lumps or bumps", the patient reported a lump under his left second toe. MRI showed a 1.8 cm soft tissue mass. A GA68-DOTA-TATE PET CT revealed a 2.3 cm soft tissue mass plantar to the 2nd left proximal phalanx with intense activity mass (SUVmax 39.8). This mass was surgically excised. Post-operative FGF23 levels were as follows: 38 pg/mL → 15 pg/mL → &amp;lt;14 pg/mL. Within 14 days, the patient's ability to rise from a seated position was markedly improved. His severe rib pain persisted for three weeks but was significantly improved by six weeks post-op. Despite treatment with 1 mcg calcitriol daily and 5000 IU vitamin D daily, he developed evidence of post-operative hungry bone syndrome with calcium 8.3 mg/dL, PTH 64 pg/mL, and alk phos 157 U/L. Conclusion Tumor-induced osteomalacia is a rare but treatable condition, presenting with severe hypophosphatemia, bone pain, bone demineralization, insufficiency fractures, and muscle weakness. Due to the nonspecific nature of the presenting symptoms, delays in diagnosis are common. Serum phosphorous should be obtained in all patients presenting with unexplained elevations in alkaline phosphatase. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Bi-directional Relationship Between Celiac Disease and Liver Chemistries: A Systematic Review and Meta-Analysis.

Previous studies have reported conflicting results regarding prevalence of elevated LC (2-70%) in celiac disease (CD). This systematic review and meta-analysis assessed the prevalence of elevated LC at time of CD diagnosis and associated response to GFD. We also report the prevalence of CD in patients with unexplained elevation of LC. Studies assessing LC (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in CD patients were eligible. Studies with < 50 cases or in pediatric populations were excluded. In total, 20 studies assessing prevalence of elevated LC in 4,265 participants with newly diagnosed CD (mean age = 35.6 ± 6.5years, 69.8% female) were included. Pooled prevalence of elevated LC was 18.7% (95% CI 13.8-24.8; I2 = 95%). Normalization of elevated LC was seen in 83.1% (95% CI 73.4-89.7; I2 = 79%, 11 studies) of patients after GFD. On meta-regression, age at CD diagnosis, gender, and Marsh grading were not associated with elevated LC. Among 979 participants (7 studies) with unexplained elevation of LC, pooled seroprevalence and biopsy-proven CD was 6.4% (95% CI 2.9-10.3, I2 = 71%) and 4.5% (95% CI 2.6-7.7, I2 = 67%), respectively. Elevated LC are seen in approximately one-fifth of patients at CD diagnosis with majority normalizing after GFD. Age, gender, and degree of intestinal damage are not predictive of elevated LC. In the appropriate clinical scenario, liver tests should be serially monitored in CD reserving workup for additional causes after a trial of GFD. Patients with unexplained elevation of liver tests should be screened for celiac disease.

Mechanisms of Coronary Ischemia in Women.

Obstructive coronary artery disease is a major cause of ischemia in both men and women; however, women are more likely to present with ischemia in the setting of no obstructive coronary arteries (INOCA) and myocardial infarction with no obstructive coronary arteries (MINOCA), conditions that are associated with adverse cardiovascular prognosis despite absence of coronary stenosis. In this review, we focus on mechanisms of coronary ischemia that should be considered in the differential diagnosis when routine anatomic clinical investigation leads to the finding of non-obstructive coronary artery disease on coronary angiography in the setting of acute myocardial infarction. There are multiple mechanisms that contribute to MINOCA, including atherosclerotic plaque disruption, coronary artery spasm, coronary microvascular dysfunction (CMD), coronary embolism and/or thrombosis, and spontaneous coronary artery dissection. Non-coronary causes such as myocarditis or supply-demand mismatch should also be considered on the differential when there is an unexplained troponin elevation. Use of advanced imaging and diagnostic techniques to determine the underlying etiology of MINOCA is feasible and helpful, as this has the potential to guide management and secondary prevention. Failure to identify the underlying cause(s) may result in inappropriate treatment and inaccurate counseling to patients. MINOCA predominates in young women and is associated with a guarded prognosis. The diagnosis of MINOCA should prompt further investigation to determine the underlying cause of troponin elevation. Patients with INOCA and MINOCA are heterogeneous, and response to treatments can be variable. Large randomized controlled trials to determine longer-term optimal medical therapy for management of these conditions are under investigation.

Multi-System Langerhans Cell Histiocytosis as a Mimic of IgG4-Related Disease: A Case Report and Literature Review

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the clonal accumulation and/or proliferation of specific dendritic cells resembling normal epidermal Langerhans cells (LCs). Clinical manifestations are variable, depending on the affected tissues or organs, however, LCH with elevated serum IgG4 has not been reported. Herein, we reported a 26-year-old Chinese female multi-system LCH (MS-LCH) who first presented with central diabetes insipidus (CDI), accompanied by panhypopituitarism and hepatic dysfunction. Diagnostic investigations were strongly suspicious of IgG4-RD because of elevated serum IgG4 levels during the process. Furtherly, thyroid and lymph node involvement and biopsy led to the diagnosis of MS-LCH; the strongly positive staining of CD1a, S100, CD207 (langerin), and Ki67 was found. Moreover, after systemic treatment with five cycles of chemotherapy, many lesions were greatly improved. Since both LCH and IgG4-RD are orphan diseases that can affect any organ, the differential diagnosis is challenging, especially when LCH is associated with unexplained serum IgG4 elevation. In this article, the case of a young woman suffering from MS-LCH that affected organs including the pituitary, thyroid, lymph node, and liver was summarized, and relevant literature was reviewed to better equip the diagnosis and treatment in its early stages.

COVID-19 vaccination and cardiac dysfunction.

The coronavirus disease 2019 (COVID-19) mRNA vaccine against severe acute respiratory syndrome coronavirus 2 infections has reduced the number of symptomatic patients globally. A case series of vaccine-related myocarditis or pericarditis has been published with extensive vaccination, most notably in teenagers and young adults. Men seem to be impacted more often, and symptoms commonly occur within 1 wk after immunization. The clinical course is mild in the majority of cases. Based on the evidence, a clinical framework to guide physicians to examine, analyze, identify, and report suspected and confirmed cardiac dysfunction cases is needed. A standardized workup for every patient with strongly suspicious symptoms associated with the COVID-19 mRNA vaccine comprises serum cardiac troponin measurement and a 12-lead electrocardiogram (ECG). For patients with unexplained elevation of cardiac troponin and pathologic ECG, echocardiography is recommended. Consultation with a cardiovascular expert and hospitalization should be considered in this group of patients. Treatment is primarily symptomatic and supportive. Deferring a 2nd dose of the COVID-19 mRNA vaccination in individuals with suspected myocarditis or pericarditis after the 1st dose is suggested until further safety data become available.