Recurrent Episodes Research Articles

MOST COMMON PATHOGENS OF OTITIS MEDIA IN PEDIATRICS AND THEIR RESISTANCE TO ANTIMICROBIAL AGENTS

Acute otitis media (AOM) stands as a prevalent child­hood illness, frequently necessitating antibiotic treatment. Its burden is significant, affecting about 80% of children under 3 years old, with approximately 40% experiencing recurrent episodes by age 3. In a study spanning Euro­pean countries, including Lithuania, middle ear otitis occurred at a rate of 160.7 cases per 100,000 children per year. Post-pneumococcal conjugate vaccine (PCV) implementation, causative agents shifted towards non-vaccine pneumococcal types and Haemophilus influen­zae. Antibiotic prescription rates, as noted from surveys of European pediatricians, range up to 78% for otitis media with effusion (OME). Commonly prescribed me­dications include amoxicillin (88.5%), amoxicillin-cla­vulanate (7.8%), cephalosporins (3.4%), and macrolides (0.3%). Despite similar antibiotic prescription frequen­cies in Eastern Europe and the Baltic, prescription practi­ces differ, influenced by active otitis monitoring. In this review article, we care to provide up to date cri­tical review of the literature on AOM prevalence, most common pathogens and antimicrobial resistance. Conclusions and recommendations. The most common pathogens of acute otitis media are Streptococcus pneu­moniae and Haemophilus influenzae, with S. pneumoniae often showing resistance to penicillin and erythromycin, while H. influenzae tends to be resistant primarily to ampicillin and amoxicillin when combined with clavu­lanic acid; however, due to increased PCV vaccination, H. influenzae is becoming more prevalent, especially among patients unresponsive to first-line treatment with amoxicillin, often due to β-lactamase-producing strains.

768. ENDOSCOPIC MANAGEMENT OF COMPLEX THORACIC AORTA ANEURYSMAL SAC AND ENDOGRAFT INFECTION ASSOCIATED WITH AORTOESOPHAGEAL FISTULA

Abstract Background Aortoesophageal fistula (AEF) is a rare but life-threatening condition. Secondary AEF is a complex pathology occurring after thoracic aorta surgery with prosthetic graft, with an incidence of 1.6%. However, this is likely to rise with the increasing number of thoracic endovascular aortic repair (TEVAR) being performed. Management of secondary AEF is more challenging due to presence of adhesions in the pleural space, co-existing endograft infection and poor physiology of this group of patients. Definitive surgery carries high mortality rate and not all patients are suitable candidates. We review a case of secondary AEF with thoracic endograft infection managed non-operatively. Methods Our patient is a 70 years old man with a background of Stanford type A aortic dissection managed with ascending aorta and hemi-arch replacement with Dacron graft. Six years later, he had frozen elephant trunk reconstruction due to aneurysmal dilatation. Three months later, he underwent TEVAR for descending thoracic aorta aneurysm. Post-operation, he was diagnosed with Flavonifractor plautii bactaeremia secondary to infected aneurysmal sac and aortic stent graft and was initiated on antimicrobial therapy. During this time patient also developed recurrent episodes of haemoptysis. Bronchoscopy excluded an aortobronchial fistula and Oesophago-gastro-duodenoscopy (OGD) confirmed AEF at 25 cm from incisors. Results After discussion with a multidisciplinary team and patient, endoscopic management was chosen over surgery. Initial endoscopic closure of AEF with over-the-scope-clip appeared satisfactory but repeat OGD showed recurrence of new AEF which was partially closed with clips. Repeat imaging showed worsening mediastinal infection with larger gas-containing cavity. OGD was repeated with contrast demonstrating fistulous connection between the oesophagus and aneurysmal sac. A 7-French 4 cm double pigtail (DPT) stent was deployed into the sac under fluoroscopy to allow for trans-oesophageal drainage. Repeat imaging showed improvement in infection (Figure 1). Patient underwent endoscopic exchange of DPT stent 2 months after the initial insertion. Conclusion Definitive surgery for secondary AEF includes drainage of infection, explantation of infected endograft and aortic and oesophageal reconstruction. Oesophagectomy is preferred over primary repair of oesophageal defect. Not all patients will be suitable candidates for radical surgery and a non-operative approach may be required. Our patient likely has dense pleural and mediastinal adhesions from previous surgeries and thus, repeat surgery will be more challenging with increased risk of complications. However, if his mediastinal infection fails to resolve despite a period of DPT stent drainage, definitive surgery involving McKeown minimally invasive oesophagectomy with substernal gastric pull up would be required. Figure 1: Image A shows a large cavity with air and coalescent locules (arrow) prior to insertion of DPT stent. Image B shows a collapsed cavity (arrow) after DPT stent insertion.

Delayed Hypersensitivity Reaction to Dermal Fillers Following mRNA COVID-19 Vaccination

Dear Editor, I wish to bring attention to a potential delayed immune reaction associated with dermal fillers in the context of mRNA COVID-19 vaccines. While severe vaccine reactions remain uncommon, the widespread administration of mRNA vaccines and the prevalent use of dermal fillers necessitate a closer examination of their possible interactions. We recently encountered a 59-year-old female patient who developed persistent facial swelling months after receiving the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine. Notably, the patient had a history of dermal filler injections, predominantly hyaluronic acid, administered three to four years prior. Despite various therapeutic interventions, including antihistamines, corticosteroids, and ACE inhibitors, she experienced recurrent episodes of swelling. Ultrasound assessment revealed the absence of residual filler material, leading us to consider an immune-mediated response potentially triggered by the mRNA vaccine. This case highlights the importance of further research into the interaction between mRNA COVID-19 vaccines and dermal fillers. It suggests that individuals with a history of dermal fillers may be susceptible to delayed inflammatory reactions post-vaccination. Clinicians should be aware of this potential adverse event, particularly when evaluating patients with unexplained facial swelling following vaccination.

A case of concurrent malnutrition in maple syrup urine disease: challenges and solutions in Indonesia

BackgroundMaple syrup urine disease (MSUD) is a rare autosomal recessive inborn error of metabolism characterised by the impaired breakdown of branched-chain amino acids. Detecting MSUD in newborns is challenging due to the lack of distinctive signs, especially in resource-limited settings like Indonesia.Case presentationA 2-year-old boy presented to the paediatric metabolic clinic with inactivity, a history of uncontrolled epilepsy, global developmental delay and moderate malnutrition. He was born at 40 weeks of gestation, weighing 3100 g, to consanguineous parents. The patient faced feeding problems and was lethargic after birth, with recurrent episodes of generalised seizure and spasticity. Diagnosed with MSUD at four months, the initial response to thiamine supplementation and MSUD Anamix formula was positive. However, weight loss occurred after switching to unregulated family food, as MSUD-specific infant formula became inaccessible and unsustainable due to high costs for the caregivers. Upon compliance with nutritional advice, the child regained weight and progressed appropriately for his age.ConclusionInborn errors of metabolism like MSUD should be considered in atypical disease presentations. In resource-limited settings, management should be tailored to local product availability and accessibility to ensure effective care.

Aseptic meningitis with recurrent headache episodes, vomiting, and central fever as first manifestation of isolated neurosarcoidosis: a case report

BackgroundNeurosarcoidosis is a rare entity, usually within the context of systematic sarcoidosis. Isolated neurosarcoidosis and especially a manifestation with pachymeningitis is a notable rarity.Case ReportA 26-year-old patient presented to the emergency department with acute onset, recurrent episodes of occipital headaches spreading over the whole cranium and vomiting without food consumption, for three days. The clinical examination did not reveal any neurological deficits. The laboratory exams showed no pathological findings. A CT examination with angiography did not detect any acute intracranial or vessel pathology. A lumbar puncture was performed to rule out subarachnoid hemorrhage. The results showed a lymphocytic pleocytosis of 400/µL, elevated protein levels of 1077 mg/dL and reduced glucose levels (CSF: 55 mg/dL, Serum: 118 mg/dL). Extensive infectiological examinations did not reveal any signs of infection, including Borrelia spp. and M. tuberculosis. No positive auto-antibodies or vasculitis-related auto-antibodies were detected. The CSF analysis showed negative oligoclonal bands but an isolated increase in β2-microglobulin, neopterin, and IL-2R levels. The MRI examination revealed a dural gadolinium-enhancement, pronounced in the basal cerebral structures and the upper segment of the cervical spine, consistent with neurosarcoidosis. Corticosteroid treatment rapidly led to a significant improvement of the symptoms. No systemic manifestations of sarcoidosis were found.ConclusionsThis case report aims to highlight aseptic meningitis with atypical, acute onset headache attacks as a possible manifestation of isolated neurosarcoidosis. Neurosarcoidosis is a clinical entity that requires prompt treatment to avoid permanent neurological deficits.

Priapism Presentations in a Saudi Arabian Emergency Department: A Retrospective Study at a Tertiary Care Hospital.

To examine the distribution, clinical characteristics, and management of priapism in a Saudi Arabian tertiary care setting to provide a regional perspective. This retrospective chart review included 29 male patients presenting with priapism at a tertiary care hospital in Riyadh, Saudi Arabia, from January 2011 to June 2023. Data were collected on patient demographics, clinical presentation, treatment modalities, and outcomes. The study found recurrent episodes of priapism in many patients, with a significant number associated with hematological diseases, notably sickle cell disease. Most treatments involved non-surgical methods. A notable finding was the correlation between the duration of priapism episodes and the likelihood of hospital admissions, suggesting that prolonged episodes often required more extensive medical attention. Priapism often presents as a chronic and recurrent condition requiring personalized management strategies. This study emphasizes the importance of recognizing regional occurrence patterns to enhance the management of priapism and suggests a need for further research in regions where this condition is less common.

Bilateral Horizontal Canal Dysplasia Presenting as Hearing Loss With Recurrent Vertigo Mimicking Meniere's Disease.

We report an extremely rare case with bilateral horizontal semicircular canal (HSC) dysplasia presenting as hearing loss with recurrent vertigo mimicking Meniere's disease in a previously healthy 49-year-old male patient. HSC malformation is one of the common isolated developmental anomalies of the bony labyrinth usually associated with varying degree of hearing loss. He suffered from recurrent episodes of vertigo lasting more than 20 minutes accompanied by left hearing loss and tinnitus for 3 years. Pure-tone audiometry revealed a mild to moderate hearing loss at low frequencies in the left ear. Bithermal caloric testing revealed significant left-sided canal paralysis, but other vestibular testing was normal. Computerized tomography (CT) of the temporal bone showed the left HSC hypoplasia lacking a central bony island fused together with an enlarged vestibule, and right dysplasia, finally diagnosed with bilateral HSC dysplasia. Meniere's disease-like recurrent vertigo attack and hearing loss were suspected to be caused by subsequent endolymphatic hydrops which could be due to HSC dysplasia.

Remote Sensing Analysis of Smog-Inducing Aerosol Optical Depth: An Integrated Approach for Air Pollution Mitigation

Aerosol aggravation poses a significant challenge in the administrative Lahore Division of Punjab, Pakistan and contributes greatly to the persistent issue of smog. Since 2017, the division has experienced recurrent episodes of smog pollution, most notably in the months of October and November. In the present study, aerosol optical depth (AOD) has been analyzed alongside three metrological parameters: temperature, humidity and rainfall. These were tracked in October and November of 2018, 2020, and 2022 using remote sensing data and satellite imaging. Additionally, anthropogenic emissions data from automobile exhaust, industries and stubble burning were derived from secondary sources. Ultimately, the study helped piece together the complex environmental picture in Lahore Division in October and November. The results showed that AOD levels not only increased during this time, they were significantly influenced by a full range of metrological variables such as low temperature, high relative humidity, lack of rainfall and emissions from a variety of human activities. It was found that trucks, tractors and buses were among the worst contributors, alongside industry and stubble burning. Therefore, the present study suggests multi sectoral plans to mitigate aerosol levels and combat the smog menace, promoting environmental sustainability in the Lahore Division. A full set of recommendation is included, divided into three categories: industry, transport and agriculture. These are focused on technology, control systems, disposal, incentives, green solutions and more. At all levels, commitment, collaboration, and coordination are absolutely vital.

Long-term efficacy of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in two patients with sJIA and recurrent episodes of MAS.

Systemic juvenile idiopathic arthritis (sJIA), a multifaceted autoinflammatory disorder, can be complicated by life-threatening conditions such as macrophage activation syndrome (MAS) and interstitial lung disease (ILD). The management of these conditions presents a therapeutic challenge, underscoring the need for innovative treatment approaches. to report the possible role of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in the treatment of multi-drug-resistant sJIA. We report two patients affected by sJIA with severe and refractory MAS and high serum IL-18 levels, responding to dual blockade of IL-1β and IL-18. The first patient is a 20-year-old man, presenting a severe MAS complicated by thrombotic microangiopathy, following SARS-CoV-2 infection. He was treated with MAS825, with quick improvement. Eighteen months later, the patient is still undergoing biweekly treatment with MAS825, associated with MTX, ciclosporin and low-dose glucocorticoids, maintaining good control over the systemic features of the disease.The second patient, a 10-year-old girl, presented a severe MAS case, complicated by posterior reversible encephalopathy syndrome (PRES), following an otomastoiditis. The MAS was not fully controlled despite treatment with IV high-dose glucocorticoids, anakinra and ciclosporin. She began biweekly MAS825, which led to a prompt amelioration of MAS parameters. After 10 months, the patient continues to receive MAS825 and is in complete remission. In light of the pivotal role of IL-1β and IL-18 in sJIA, MAS and ILD, MAS825 might represent a possible valid and safe option in the treatment of drug-resistant sJIA, especially in the presence of high serum IL-18 levels.

Idiopathic Systemic Capillary Leak Syndrome: Report of a Pediatric Case.

The idiopathic systemic capillary leak syndrome is characterized by recurrent episodes of hypovolemia, with an unknown cause, presenting as a distributive and hypovolemic shock, due to fluid loss to the extravascular space. We describe a case of a previously healthy seven-year-old boy, who started with prodromal symptoms (abdominal pain, fatigue, nausea), followed by a fluid extravasation phase, with hemoconcentration, hypoproteinemia, and muscular edema in the abdominal wall and lower limbs, accompanied by pain - compartment syndrome. After a couple of days, spontaneous and fast recovery was noted, with clinical and analytic improvement. The inflammatory markers were always normal, and the blood cultures were negative. In this case, it is possible to distinguish the three idiopathic systemic capillary leak syndromes phases, as described in the literature. Although rare, this syndrome can be fatal, and the differential diagnosis with other causes of shock represents a challenge.

Corticosteroid therapy for nephrotic syndrome in children.

In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. Children with untreated nephrotic syndrome frequently die from infections. The majority of children with nephrotic syndrome respond to corticosteroids. However about 70% of children experience a relapsing course with recurrent episodes of oedema and proteinuria. Corticosteroid usage has reduced the mortality rate in childhood nephrotic syndrome to around 3%, with infection remaining the most important cause of death. However corticosteroids have known adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis and adrenal suppression. The original treatment schedules for childhood nephrotic syndrome were developed in an ad hoc manner. The optimal doses and durations of corticosteroid therapy that are most beneficial and least harmful have not been clarified. The aim of this review was to determine the benefits and harms of different corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), Cochrane Renal Group Specialised Register (July 2002), MEDLINE (1966 - July 2002) and EMBASE (1980 - July 2002) without language restriction, reference lists of articles, abstracts from conference proceedings and contact with known investigators in the area. Randomised controlled trials were included if they were carried out in children (aged three months to 18 years) in their initial or subsequent episode of SSNS, if they compared different durations, total doses or other dose strategies using prednisone or other corticosteroid agent and if they had outcome data at six months or more. Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality and extracted data. The principle outcome measure was the number of children with and without relapse after six and 12-24 months. Secondary outcomes sought included the number of children who developed frequently relapsing nephrotic syndrome and adverse events. A random effects model was used to estimate summary effect measures (relative risk (RR), risk difference (RD)) after testing for heterogeneity. Meta-regression was used to explore potential between-study differences due to the baseline risk of relapse, study quality and types of interventions used. Nineteen trials have been included in this review. A meta-analysis of six trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12 - 24 months (RR 0.70; 95% CI 0.58 to 0.84) without an increase in adverse events. There was an inverse linear relationship between the duration of treatment and risk of relapse (RR = 1.26 - 0.112 duration; r(2) = 0.56; p = 0.03). The number of children who became frequent relapsers and the mean relapse rate/patient/year were also significantly reduced without increase in serious adverse events. In children with frequently relapsing nephrotic syndrome, deflazacort was significantly more effective in maintaining remission than prednisone (RR 0.44; 95% CI 0.25 to 0.78). Children in their first episode of SSNS should be treated for at least three months with an increase in benefit being demonstrated for up to seven months of treatment. In a population with a baseline risk for relapse following the first episode of 60% with two months of prednisone, daily prednisone for four weeks followed by alternate day therapy for six months would be expected to reduce the number of children experiencing a relapse by about 33%. In children who relapse frequently, deflazacort deserves further study.

The genetic association between bipolar disorder and dementia: a qualitative review.

Bipolar disorder is a chronic disorder characterized by fluctuations in mood state and energy and recurrent episodes of mania/hypomania and depression. Bipolar disorder may be regarded as a neuro-progressive disorder in which repeated mood episodes may lead to cognitive decline and dementia development. In the current review, we employed genome-wide association studies to comprehensively investigate the genetic variants associated with bipolar disorder and dementia. Thirty-nine published manuscripts were identified: 20 on bipolar disorder and 19 on dementia. The results showed that the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A were overlapping between patients with bipolar disorder and dementia. In conclusion, the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A may be associated with the neuro-progression of bipolar disorder to dementia. Further genetic studies are needed to comprehensively clarify the role of genes in cognitive decline and the development of dementia in patients with bipolar disorder.

Machine Learning-Driven Evaluation of Lithium and Valproate Combination Therapy in Bipolar Disorder

Background Bipolar disorder (BD) is characterized by recurrent episodes of mania and depression, requiring long-term mood stabilization. While lithium is a well-established treatment for BD, its efficacy can vary among individuals. Combination therapy with valproate has been explored to enhance treatment outcomes. Objective This case series aims to demonstrate the superior effectiveness of lithium and valproate combination therapy over lithium monotherapy in stabilizing mood in patients with bipolar disorder. Methods This retrospective study includes data from 2 patients diagnosed with bipolar disorder. Patients initially treated with lithium monotherapy who showed inadequate response were subsequently treated with a combination of lithium and valproate. Clinical assessments were conducted using the Mood Disorder Questionnaire (MDQ), Clinical Global Impression-Severity (CGI-S), Hamilton Depression Rating Scale (HDRS), and Global Assessment of Functioning (GAF) before and after combination therapy. Results Combination therapy with lithium and valproate significantly improved mood stability in patients compared to lithium monotherapy. On average, MDQ scores decreased from 22.4 to 8.3, CGI-S scores improved from 4.8 to 2.1, HDRS scores reduced from 25.6 to 9.7, and GAF scores increased from 50.3 to 75.4. These improvements were sustained over a followup period of 12 months. The combination of lithium and valproate provides superior mood stabilization in patients with bipolar disorder compared to lithium alone. These findings suggest that combination therapy should be considered in patients who do not achieve adequate symptom control with lithium monotherapy

Machine Learning-Driven Evaluation of Antidepressant and Mood Stabilizer Combination Therapy in Bipolar Disorder

Background Bipolar disorder (BD) is characterized by recurrent episodes of mania and depression, requiring long-term mood stabilization. While mood stabilizers such as lithium and valproate are the cornerstone of BD treatment, the use of antidepressants in combination with mood stabilizers has been explored to enhance therapeutic outcomes, particularly in managing depressive episodes. Objective This case series aims to demonstrate the superior effectiveness of antidepressants combined with mood stabilizers over mood stabilizers alone in stabilizing mood in patients with bipolar disorder. Methods Two patients with bipolar disorder who initially received mood stabilizers monotherapy and exhibited suboptimal responses were subsequently treated with a combination of mood stabilizers and antidepressants. Clinical assessments were conducted using the Mood Disorder Questionnaire (MDQ), Clinical Global Impression-Severity (CGI-S), Hamilton Depression Rating Scale (HDRS), and Global Assessment of Functioning (GAF) before and after combination therapy. Results Combination therapy with antidepressants and mood stabilizers significantly improved mood stability in both patients compared to mood stabilizers alone. MDQ scores decreased, CGI-S scores improved, HDRS scores reduced, and GAF scores increased, with improvements sustained over a follow-up period of 12 months. Conclusion The combination of antidepressants and mood stabilizers provides superior mood stabilization in patients with bipolar disorder compared to mood stabilizers alone. These findings suggest that combination therapy should be considered in patients who do not achieve adequate symptom control with mood stabilizers monotherapy

Staphylococcus epidermidis isolated sphenoiditis: a rare cause of recurrent orbital apex syndrome

Isolated sphenoid sinusitis (ISS) is a rare condition that can lead to severe complications, with orbital apex syndrome (OAS) being an exceptionally rare manifestation characterized by visual loss and multiple cranial neuropathies. We report a case of a 41-year-old female presenting with recurrent OAS caused by a chronic Staphylococcus epidermidis infection of the sphenoid sinus. Despite extensive diagnostic workups and multiple surgical interventions, the patient experienced recurrent episodes of OAS, highlighting the challenges in diagnosis and treatment. This report emphasizes the pathogenic potential of S. epidermidis, typically considered a commensal organism, in chronic sinusitis and underscores the importance of a multidisciplinary approach in managing such complex cases.

Impact of Psychoeducation Applied to The Spouses of Bipolar Patients on Their Emotional Expression, Stigmatization, and Loneliness Levels

Objective: Bipolar disorder (BD) is a serious burden for patients and family members due to recurrent mood episodes, hospitalizations, and loss of productivity. The goal of this study is to examine how psychoeducation affected the caregivers of bipolar patients' levels of emotional expression, stigmatization, loneliness, and mood symptoms. Method: This research is a quasi-experimental intervention study applied as a pretest-posttest design with a control group. The study included 20 patients with bipolar diagnosis and 20 caregiver spouses who were followed up in our outpatient clinic. Participants were divided into 2 groups as study and control group. The spouses in the control group were interviewed only to evaluate their situation. The study group received a 6-session (15 hours) psychoeducation intervention. We administered the Emotion Expression Scale (EES), Self-Stigma Scale-Family (SSI-F), UCLA Loneliness Scale (UCLA-LS), and DASS-21 Scale to the spouses of bipolar patients in the study and control groups before and after the psychoeducation program. Results: The mean age of the spouses in the study group was 43.4±7.04 years, the mean age of the spouses in the control group was 39±8.29 years and all of them were female. There was no significant difference between the mean scores of the SSI-F, EES, and DASS-21 scales of the spouses in the study and control groups before the training (p>0.05). After the psychoeducation program was applied to the spouses in the intervention group, a significant decrease was observed in the SSI-F, EES, and DASS-21 scale scores (p

Intestinal glucagon-like peptide-1: A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice.

Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions. However, the patho-genesis of hypoglycaemic counterregulation is still unclear. Glucagon-like peptide-1 (GLP-1) and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus (T1DM). The role of GLP-1 in counterregulatory dys-function during hypoglycaemia in patients with T1DM has not been reported. To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice. T1DM was induced in C57BL/6J mice using streptozotocin, followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia (DH5). Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon (GCG) secretion. The GLP-1 receptor agonist GLP-1(7-36) or the antagonist exendin (9-39) were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice. The expression levels of intestinal GLP-1 and its receptor (GLP-1R) were significantly increased in DH5 mice. Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex, leading to dysfunction of adrenal counterregulation during hypoglycaemia. DH5 mice showed increased pancreatic δ-cell mass, cAMP levels in δ cells, and plasma somatostatin concentrations, while cAMP levels in pancreatic α cells and plasma GCG levels decreased. Furthermore, GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group. Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway. Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia, leading to reduced appetite and compromised secretion of adrenaline, noradrenaline, and GCG during hypo-glycaemia.

Recurrent Pulmonary Tuberculosis in China, 2005 to 2021

Despite posing a significant challenge to global tuberculosis (TB) elimination efforts, recurrent TB remains understudied due to the challenges of long-term observation. To investigate the burden of recurrent TB using data from patients with pulmonary TB (PTB) in China. This retrospective cohort study included all bacteriologically confirmed or clinically diagnosed PTB cases reported to the Tuberculosis Information Management System with completed or successful treatment outcomes from January 1, 2005, to December 31, 2021. Data were analyzed from July 15, 2022, to October 28, 2023. Newly diagnosed PTB was classified into primary, hematogenous disseminated, or secondary PTB. The primary outcome was the annual recurrence rate, stratified by disease classification, over the 17-year observation period. The recurrence rate for year n was calculated by dividing the number of patients with recurrent TB in year n by observed person-years in year n. The secondary outcome was the annual proportion of recurrent TB among reported cases and associated risk factors. Of 13 833 249 patients with TB reported to the Tuberculosis Information Management System, 10 482 271 with PTB met the inclusion criteria. Of these, 68.9% were male, 22.3% were 65 years or older, 89.6% were of Han ethnicity, and 68.4% were agricultural workers. A total of 413 936 patients experienced a recurrent TB episode after successful treatment, resulting in an overall recurrence rate of 0.47 (95% CI, 0.47-0.48) per 100 person-years. The recurrence rate for patients with primary PTB was 0.24 (95% CI, 0.22-0.26) per 100 person-years; for hematogenous disseminated PTB, 0.37 (95% CI, 0.36-0.38) per 100 person-years; and for secondary PTB, 0.48 (95% CI, 0.47-0.48) per 100 person-years. The cumulative proportion of recurrences within the first 2 years accounted for 48.9% of all recurrent cases. The proportion of recurrent cases among notified incident cases increased 1.9-fold from 4.7% in 2015 to 8.8% in 2021. Among other factors, ages 45 to 64 years (adjusted hazard ratio, 1.77 [95% CI, 1.65-1.89]) and having completed treatment (adjusted hazard ratio, 1.16 [95% CI, 1.14-1.18]) were identified as associated with recurrence. In this retrospective cohort study, the PTB recurrence rate was substantially higher than the incidence, and the proportion of recurrent cases increased. Almost half of the recurrence occurred within the first 2 years, suggesting that routine posttreatment follow-up may represent an important strategy for accelerating TB elimination.

Identification and optimisation of perioperative factors for patients with von Willebrand disease undergoing elective total hip and knee arthroplasty.

Von Willebrand disease stands as the most prevalent bleeding disorder seen in both medical and surgical practice. Due to recurrent bleeding episodes within the joints, many patients endure arthropathy, leading to substantial pain and restricted function. Total joint arthroplasty emerges as a final option for managing such cases. Nevertheless, the existence of von Willebrand disease presents several challenges in this regard. This review aims to explore the perioperative strategies tailored for patients with von Willebrand disease undergoing elective total joint arthroplasty.

Cellular mechanisms of acute rhabdomyolysis in inherited metabolic diseases.

Acute rhabdomyolysis (RM) constitutes a life-threatening emergency resulting from the (acute) breakdown of skeletal myofibers, characterized by a plasma creatine kinase (CK) level exceeding 1000 IU/L in response to a precipitating factor. Genetic predisposition, particularly inherited metabolic diseases, often underlie RM, contributing to recurrent episodes. Both sporadic and congenital forms of RM share common triggers. Considering the skeletal muscle's urgent need to rapidly adjust to environmental cues, sustaining sufficient energy levels and functional autophagy and mitophagy processes are vital for its preservation and response to stressors. Crucially, the composition of membrane lipids, along with lipid and calcium transport, and the availability of adenosine triphosphate (ATP), influence membrane biophysical properties, membrane curvature in skeletal muscle, calcium channel signaling regulation, and determine the characteristics of autophagic organelles. Consequently, a genetic defect involving ATP depletion, aberrant calcium release, abnormal lipid metabolism and/or lipid or calcium transport, and/or impaired anterograde trafficking may disrupt autophagy resulting in RM. The complex composition of lipid membranes also alters Toll-like receptor signaling and viral replication. In response, infections, recognized triggers of RM, stimulate increased levels of inflammatory cytokines, affecting skeletal muscle integrity, energy metabolism, and cellular trafficking, while elevated temperatures can reduce the activity of thermolabile enzymes. Overall, several mechanisms can account for RMs and may be associated in the same disease-causing RM.