To evaluate plasma and aqueous humor angiotensin-converting enzyme (ACE) and transforming growth factor-β1 (TGFβ1) levels in patients with proliferative vitreoretinopathy (PVR) secondary to rhegmatogenous retinal detachment (RRD). Eighty-eight patients were divided into three groups: RRD without PVR (non-PVR, n = 36), RRD with PVR (PVR, n = 32), and controls (n = 20). Plasma and aqueous ACE and TGFβ1 levels were quantified using ELISA. Group comparisons, regression, and ROC analyses were performed to determine associations with PVR. Age and sex did not differ among groups (p > 0.05). Median aqueous ACE levels were significantly higher in PVR and non-PVR eyes than in controls (both p < 0.001), though the PVR-non-PVR difference was nonsignificant (p = 0.411). Aqueous TGFβ1 levels were markedly elevated in the PVR group versus both others (p < 0.001). Plasma ACE and TGFβ1 did not differ among groups (p > 0.05). Aqueous TGFβ1 demonstrated strong discriminative performance for PVR within this cohort (AUC = 0.92; cutoff 132.0 ng/L; sensitivity 93.8%; specificity 72.2%). Multivariate analysis identified aqueous TGFβ1 (OR = 1.047, p = 0.002) and symptom duration >30 days (OR = 77.6, p = 0.014) as independent predictors. Aqueous ACE and TGFβ1 were positively correlated, although this association did not reach statistical significance (ρ = 0.230, p = 0.059). Aqueous ACE and TGFβ1 levels were elevated in eyes with RRD. TGFβ1 was significantly associated with PVR, whereas ACE elevation appeared to reflect intraocular changes related to RRD rather than a PVR-specific process.

An 18-year-old female patient with no past medical history presented with nonanginal chest pain 2 months after her delivery. She did not report any other symptoms such as cough, dyspnea, nausea, or vomiting. Her vital signs were stable. The only positive finding on physical examination was tenderness and edema, with a palpable lump on her right thigh. Other examinations did not provide any additional information. Her lab results showed elevated calcium (12.5 mg/dL), low parathyroid hormone (5.6 pg/mL), and near-normal 25-(OH) Vitamin D levels (27.4 ng/dL). The core needle biopsy of the right thigh muscle revealed patchy lymphocytic infiltration with giant cells, without caseous necrosis, suggestive of sarcoidosis. The patient also had elevated angiotensin-converting enzyme levels. The computed tomography of the lungs revealed no pulmonary involvement or hilar lymphadenopathy. The patient was treated with 30 mg of prednisolone daily. One month later, her symptoms improved, and calcium levels returned to normal.

Celastrol (CSL), a natural triterpenoid extracted from Tripterygium wilfordii, demonstrates a wide range of biological activities. In this study, we explored whether CSL alleviates kidney damage in spontaneously hypertensive rats (SHRs) through the modulation of the Nrf2/Ho-1 pathway, a crucial target in renal injury models. A total of 40 male SHRs, aged 6–8 weeks, were randomly allocated to four groups: the control group (CON, serving as the healthy control), the spontaneously hypertensive rat group (SHR), the SHR group treated with low-dose CSL (L-CSL + SHR, 0.5 mg/kg/d), and the SHR group treated with high-dose CSL (H-CSL + SHR, 1 mg/kg/d). All drugs were formulated using physiological saline as the solvent and administered via intraperitoneal injection. The control group received an equivalent volume of physiological saline via intraperitoneal injection, and all groups underwent continuous daily administration for 6 weeks. The results indicated that, in comparison with the control group, the serum levels of angiotensin, angiotensin-converting enzyme, and aldosterone in the SHR group were relatively high, and CSL treatment further downregulated these indices. Simultaneously, CSL downregulated pro-inflammatory factors (tumor necrosis factor-α and interleukin-1β) and upregulated interleukin-6. Regarding renal function-related indicators, CSL reduced malondialdehyde levels and enhanced the activities of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase. Moreover, CSL inhibited the overexpression of Keap1. Significantly, the mRNA levels of Nrf2, Nqo1, and Ho-1 in the CSL-treated groups were notably higher than those in the SHR group. These findings suggest that CSL mitigates renal pathological damage in SHR by activating the Nrf2/Ho-1 pathway, offering a potential therapeutic approach for hypertension-induced renal injury.

Abstract Background Sarcoidosis-associated hypercalcemia can cause acute kidney injury (AKI); however, reports of severe cases superimposed on advanced chronic kidney disease (CKD) stage G4 requiring hemodialysis (HD) are rare. We report a case that offers important clinical insights into diagnostic pitfalls in patients with CKD and the clinical approach to identify reversible “treatable AKI.” Case presentation A man in his seventies with baseline CKD stage G4 (serum creatinine [Cr] 2.3–2.6 mg/dL, estimated glomerular filtration rate [eGFR] 19.0–23.0 mL/min/1.73m 2 ) due to nephrosclerosis was emergently admitted for moderate hypercalcemia (corrected serum calcium 13.3 mg/dL) and AKI (Cr 5.15 mg/dL, eGFR 9.3 mL/min/1.73m 2 ). Endocrinological examination revealed suppressed intact parathyroid hormone (PTH) and elevated 1,25-dihydroxyvitamin D (1,25(OH) 2 D), leading to a diagnosis of PTH-independent, vitamin D-dependent hypercalcemia. Although serum angiotensin-converting enzyme (ACE) levels were within the normal range, this was considered to be masked by the chronic use of an ACE inhibitor (imidapril). A clinical diagnosis of sarcoidosis was made on the basis of markedly elevated soluble IL-2 receptor and lysozyme levels and mediastinal lymphadenopathy. Owing to his poor general condition, tissue biopsy could not be performed. Emergency HD was promptly initiated, followed by corticosteroid therapy with prednisolone (30 mg/day) once the clinical diagnosis was strongly suspected. Following treatment, hypercalcemia normalized rapidly, and kidney function gradually improved, allowing liberation from dialysis after five HD sessions. Conclusions When encountering unexplained AKI with hypercalcemia in patients with CKD, clinicians should consider sarcoidosis as a potential underlying cause. Additionally, clinicians will perform a multifaceted evaluation including 1,25(OH) 2 D measurement. Even in severe cases requiring dialysis, early diagnosis and appropriate treatment can render the condition a “treatable AKI.”

Objective: The COVID-19 pandemic has strained healthcare systems and has been associated with substantial morbidity and mortality. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), implicating dysregulation of the renin-angiotensin system (RAS) in COVID-19 pathophysiology. Measurement of circulating RAS components, including ACE and ACE2, may therefore provide an insight into disease severity and underlying mechanisms. Subjects and Methods: In this retrospective cohort study, 224 adults with PCR-confirmed COVID-19 were stratified by World Health Organization disease-severity criteria into asymptomatic, mild, mild-pneumonia, severe, and critical groups. Plasma ACE and ACE2 concentrations were quantified by ELISA. Demographic, clinical, and laboratory data were extracted from electronic medical records. Results and Conclusions: Increasing disease severity was associated with higher mortality, elevated body mass index, and higher viral load estimates. Severe and critical illness was characterized by leukocytosis with neutrophilia, marked lymphopenia, anemia, elevated inflammatory and coagulation markers, renal dysfunction, and hypoalbuminemia. Plasma ACE2 levels declined progressively with increasing severity and were significantly lower in patients with mild-pneumonia, severe, or critical illness compared with asymptomatic or mild cases, showing a strong inverse correlation with severity. In contrast, plasma ACE levels increased significantly with disease severity. The resulting increase in the ACE/ACE2 ratio indicates a progressive shift toward the pro-inflammatory arm of the RAS, providing mechanistic insight into the COVID-19 pathophysiology.

Multiple sclerosis (MS) is the most prevalent autoimmune neurodegenerative heterogeneous disease affecting young adults, and angiotensin-converting enzyme 2 (ACE2) is a potential biomarker in MS. To compare serum levels of ACE2 between MS patients and healthy controls, and to investigate the relationships between ACE2 gene polymorphisms (rs2074192 and rs2285666) and MS susceptibility and clinical characteristics in a Jordanian population. A case-control study was conducted. Enzyme-linked immunosorbent assay (ELISA) was used to measure ACE2 levels in the serum of 88 MS patients and 87 controls. Genotyping of rs2074192 and rs2285666 polymorphisms was performed for 498 MS patients and 504 healthy controls by Illumina HiSeq xTen system (Illumina Platform) technique. Genetic analyses were sex-stratified and used X-chromosome–appropriate coding, with Hardy–Weinberg equilibrium assessed in females only. After adjustment for covariates, log(ACE2) serum levels were significantly higher in MS patients compared to healthy controls (p < 0.001). The ACE2 rs2074192 TT genotype (p = 0.003), and T allele (p < 0.001) are significantly associated with cases. Significant associations were found between cases and the ACE2 rs2285666 CC genotype (p = 0.037), and C allele (p = 0.040). Significant associations were revealed between rs2074192 genotype and EDSS level (p = 0.036), and between rs2285666 genotype and current treatment with DMT (p = 0.022). MS patients had higher ACE2 serum levels than healthy controls and ACE2 is a susceptibility gene for MS in the Jordanian population.

Purpose The objective of this study is to elucidate the involvement of the local renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of rhegmatogenous retinal detachment (RRD) accompanied by proliferative vitreoretinopathy (PVR), with a specific focus on vitreous concentrations of renin, angiotensinogen, and angiotensin-converting enzyme (ACE). Methods In this prospective observational study, 75 patients were divided into three groups: advanced-stage PVR with RRD (n = 25), early stage PVR with RRD (n = 25), and epiretinal membrane (ERM) controls (n = 25). At the commencement of pars plana vitrectomy, undiluted vitreous samples were aspirated and analyzed for renin, angiotensinogen, and ACE concentrations using ELISA. Statistical comparisons were conducted using Kruskal–Wallis, Mann–Whitney U, and multinomial logistic regression analyses. Results ACE levels were markedly elevated in the advanced-stage PVR group compared to both early-stage PVR (p = 0.006) and control groups (p = 0.011). No significant differences were observed in renin or angiotensinogen levels among the three groups. Pseudophakic patients exhibited significantly higher angiotensinogen levels than phakic patients (p = 0.009). Each unit rise in ACE level was linked to a 73-fold greater risk of developing advanced-stage PVR, as demonstrated by multinomial logistic regression (p = 0.003). Conclusions The significant elevation of ACE in advanced PVR cases suggests a potential role for local RAAS activation in disease progression. These findings support further investigations of RAAS modulation as a candidate for therapeutic intervention in PVR.

Sarcoidosis, a rare inflammatory multisystemic disease more prevalent among females, is characterised by noncaseating granulomas affecting organs like the lungs, liver, lymph nodes, skin, and eyes. Diagnosis is through exclusion, ruling out infections, malignancies, and environmental factors. It involves an inflammatory response in a genetically susceptible host. Clinical presentations range from asymptomatic to organ failure, including skin lesions, ocular manifestations, and neurological involvement. Granuloma formation is the pathological hallmark, and chest radiograph using Scadding staging is common for the diagnosis of pulmonary sarcoidosis. A rare case of splenic involvement in sarcoidosis is presented in a 50-year-old diabetic, hypertensive, and hypothyroid female. She reported significant weight loss, decreased appetite, generalised weakness, bilateral knee and ankle pain, fever, dry cough, chest pain, exertional breathlessness, neck swelling, and maculopapular lesions on her upper limbs. Examination revealed palpable cervical lymph nodes (1.5×1 cm) and hepatosplenomegaly. Investigations showed microcytic hypochromic anaemia, hypokalaemia, elevated alkaline phosphatase, and bilateral hilar lymphadenopathy on chest X-ray. Tests for tuberculosis and connective tissue disorders were negative. Elevated serum calcium and angiotensin-converting enzyme (ACE) levels, along with noncaseating granulomas on lymph node and skin biopsies, confirmed sarcoidosis. Computed tomography (CT) scans revealed hepatomegaly with liver and spleen lesions and enlarged lymph nodes in the mediastinum, bilateral axillae, para aortic, aorto-caval, and bilateral inguinal locations. The patient received symptomatic treatment, followed by oral steroids and methotrexate with folic acid supplementation. She improved symptomatically and was discharged with instructions for regular follow-up. Prompt identification of sarcoidosis is crucial, as it often goes undetected, its closest mimic being tuberculosis. Treatment starts with steroids and may include immunosuppressive or anti-tumour necrosis factor (anti-TNF) alpha agents, significantly benefiting the patient.

A 45-year-old Japanese woman had sudden-onset subarachnoid hemorrhage and subsequently developed recurrent intracerebral hemorrhages and multiple infarctions in the left and right cerebral hemispheres, respectively. Angiotensin-converting enzyme (ACE) levels in the cerebrospinal fluid (CSF) were elevated, and a pathological examination of brain biopsy samples demonstrated multinucleated giant cell infiltration and epithelial granuloma formation in thickened pial vessel walls. After treatment with intravascular methylprednisolone 1,000 mg for 3 days, followed by oral prednisolone, she had no recurrence of cerebrovascular events. Although systemic involvement was lacking, isolated neurosarcoidosis was diagnosed based on increased ACE levels in the CSF and pathological findings.

Sarcoidosis is a granulomatous inflammatory disease primarily affecting the lungs. Central nervous system involvement is rare, occurring in approximately 5-10% of cases. Isolated lesions of the cranial nerve, particularly affecting the trigeminal nerve, are even less common. These lesions can closely resemble more well-known tumors, such as trigeminal schwannomas, meningioma, and multiple sclerosis, which can complicate diagnosis when a solitary mass in Meckel's cave is the initial finding. We report a case of a 45-year-old white man who presented with several months of right facial discomfort and numbness in the mandibular (V3) distribution consistent with trigeminal neuralgia. Magnetic resonance imaging of the brain revealed an avidly contrast-enhancing lesion in the right Meckel's cave along the trigeminal nerve. The patient underwent a skull base surgical exploration and resection. Histopathological, immunohistochemistry, and infectious screening of the resected tissue demonstrated noncaseating granulomas with no evidence of neoplastic or infectious etiologies. Lab work of angiotensin-converting enzyme levels and inflammatory markers were within normal limits. Importantly, the patient had presented with isolated trigeminal neurological symptoms, and thoracic abnormalities of mediastinal and hilar calcified lymph nodes with perilymphatic nodules were discovered only during the postoperative systemic evaluation prompted by the histopathological diagnosis. The patient started high-dose corticosteroid therapy following the operation, and his trigeminal pain and neurological symptoms improved substantially; he remained stable for the entirety of the 12-month follow-up duration. This case highlights the diagnostic challenges of trigeminal nerve lesion. There are no specific imaging features on magnetic resonance imaging that reliably distinguish neurosarcoidosis from tumors such as schwannomas or meningiomas. Therefore, neurosarcoidosis should be included in the differential diagnosis of contrast-enhancing Meckel's cave masses, even in patients without known systemic sarcoidosis. Tissue biopsy can be invaluable in determining inflammatory lesions and preventing overly aggressive resections. Once diagnosed, neurosarcoidosis is typically managed with high-dose corticosteroids and follow-up, often leading to symptom improvement. Timely histological confirmation and collaborative, multidisciplinary management are essential for achieving correct diagnosis and favorable outcomes.

Angiotensin converting enzyme (ACE) regulates blood pressure via the renin-angiotensin and bradykinin systems. Though synthetic ACE inhibitors are more effective, they pose several side effects. Methyl palmitate (MP), a natural fatty acid methyl ester with cytoprotective, antioxidant, anti-inflammatory, and vasodilatory properties, is not explored for its ACE inhibitory or antihypertensive potential. This study aimed to investigate the in vitro ACE inhibition of MP and its effect on L-NG-Nitro Arginine Methyl Ester (<sc>L</sc>-NAME)-induced hypertensive male Wistar rats. An in vitro ACE inhibition assay was conducted to compare the inhibition potency of MP with that of lisinopril. Male Wistar rats (n = 35, 7 per group) were grouped into control, disease control, and treatment groups receiving 100, 150, or 200 mg/kg/day of MP for 21 days each. Blood pressure, serum ACE activity, malondialdehyde (MDA), and nitric oxide (NO) levels in kidney tissue homogenate, and thoracic aorta histopathology were assessed. MP inhibited ACE by 61.05% at 5 µ<sc>m</sc>, exceeding lisinopril's 41.67%. High-dose MP significantly reduced serum ACE and MDA levels, while increasing NO (p < 0.001). Histopathology revealed near-normal vasculature, although changes in blood pressure were not statistically significant (p > 0.05). MP demonstrates strong natural ACE inhibition, antioxidant, and vascular protective effects, supporting further research for therapeutic optimization.

We report the case of a 48-year-old Caucasian male who presented with progressive bilateral visual decline over more than three months. He was diagnosed with birdshot chorioretinopathy (BSCR) according to the Standardization of Uveitis Nomenclature (SUN) criteria, based on characteristic fundus findings and HLA-A29 positivity. Laboratory investigations, including angiotensin-converting enzyme (ACE) and soluble IL-2 receptor levels, were within normal limits and infectious serologies were negative. Thoracic imaging by computed tomography showed no signs suggestive of sarcoidosis or infection, and pulmonary function testing was normal. Systemic corticosteroids combined with methotrexate improved vitritis but left cystoid macular edema (CME) largely unchanged, especially in the right eye. Therapy was therefore switched to mycophenolate mofetil and adalimumab, which produced a marked reduction of CME, although some cystic changes persisted. This case highlights the therapeutic challenges in the real-world management of BSCR complicated by persistent CME. Even with reduction of intraocular inflammation, CME may remain resistant to systemic corticosteroids alone, particularly in patients presenting late in the disease course. Early diagnosis, exclusion of systemic mimics, and a flexible, imaging-guided approach to treatment are essential for optimising visual prognosis.

Background/Objectives: Olfactory dysfunction and dysgeusia are common neurosensory manifestations of Coronavirus Disease 2019 (COVID-19), affecting approximately 60% of patients. These symptoms have been mechanistically linked to receptors involved in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) cell entry, including angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), furin, and neuropilin-1 (NRP1), which are highly expressed in the olfactory epithelium. Nevertheless, clinical evidence supporting a direct association between receptor expression and sensory impairment remains inconsistent. Methods: We conducted a multicenter, observational, cross-sectional study including 104 adults with polymerase chain reaction-confirmed SARS-CoV-2 infection during the first and second pandemic waves. Approximately 75 days after diagnosis, nasal and/or pharyngeal samples were obtained to quantify gene expression levels of ACE2, TMPRSS2, furin, and NRP1 using quantitative polymerase chain reaction. Olfactory dysfunction and dysgeusia were recorded as dichotomous variables. Logistic regression analyses were performed with adjustment for age, sex, and race, considering receptor expression as continuous variables and as tertiles. Missing data were addressed using multiple imputation methods. Results: Olfactory dysfunction was reported by 37.5% of participants, and dysgeusia by 36.5%. No statistically significant associations were observed between baseline expression levels of ACE2, TMPRSS2, furin, or NRP1 and the presence of olfactory dysfunction or dysgeusia in either adjusted continuous or categorical models. Although these associations did not reach statistical significance, higher ACE2 and furin expression showed a nonsignificant trend toward an increased probability of sensory alterations, whereas intermediate NRP1 levels were associated with lower disease severity. Conclusions: COVID-19-related olfactory dysfunction and dysgeusia do not appear to be directly determined by isolated baseline expression of SARS-CoV-2 entry receptors. These findings support a multifactorial and dynamic pathophysiological model involving temporal receptor regulation, inflammatory processes, and host-related factors, highlighting the need for longitudinal and interventional studies.

Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non-caseating granulomas, most commonly affecting the lungs and intrathoracic lymph nodes. Angiotensin-converting enzyme (ACE) levels and calcium abnormalities are recognized biomarkers, while ^18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is increasingly used to assess disease activity. However, neither provides sufficient diagnostic accuracy alone. Therefore, this study aimed to investigate the relationship between FDG-PET/CT metabolic findings and serum ACE and calcium (Ca2+) levels as surrogate indicators of inflammatory metabolic intensity in sarcoidosis. Methods: In this retrospective single-center study, 127 patients with pulmonary sarcoidosis who underwent PET/CT at diagnosis were evaluated. Demographic and clinical data, ACE, and Ca2+ levels were recorded. FDG uptake in mediastinal, pulmonary, and extrapulmonary sites was analyzed, and correlations with biomarkers were assessed. Results: The cohort included 89 females (70.1%) and 38 males (29.9%), mean age 51.3 ± 11.9 years. FDG uptake was most frequent in mediastinal lymph nodes (84.3%) and lung parenchyma (40.9%). ACE levels correlated weakly with total SUVmax (r = 0.214, p = 0.019). Calcium levels correlated with extrapulmonary SUVmax (r = 0.327, p = 0.001) and were higher in patients with extrapulmonary involvement (p = 0.045). No associations were found between symptom presence and biomarkers or SUVmax values. Conclusions: FDG-PET/CT metabolic parameters, particularly total and extrapulmonary SUVmax, demonstrated modest yet statistically significant associations with ACE and calcium levels. These findings suggest that a combined biomarker-imaging approach may provide complementary information regarding inflammatory metabolic intensity and systemic involvement; however, the results should be interpreted as exploratory and require validation in prospective studies.

Smoking is a significant risk factor for various cardiovascular and respiratory diseases, impacting key biomarkers such as Angiotensin-Converting Enzyme 2 (ACE-2) and Interleukin-6 (IL-6). ACE-2 is crucial for regulating blood pressure and cardiovascular health, while IL-6 is a cytokine involved in inflammatory responses. Recent research indicates that smoking disrupts the renin-angiotensin system, potentially lowering ACE-2 levels and exacerbating systemic inflammation. This study aimed to investigate the relationship between smoking and these biomarkers, shedding light on the underlying pathophysiological processes and informing targeted interventions for smokers at risk of inflammatory and cardiovascular diseases. The study involved 100 participants, including 50 smokers and 50 healthy controls, with significant differences observed in physiological and biochemical parameters such as systolic blood pressure, hemoglobin, packed cell volume, ACE-2, and IL-6 levels. Results showed that smokers had higher systolic blood pressure, hemoglobin, and PCV, alongside elevated ACE-2 and IL-6 levels, indicating chronic inflammation and cardiovascular risk. Furthermore, positive correlations were found between smoking frequency and duration with these health parameters, emphasizing the detrimental effects of smoking on overall health. These findings underscore the urgent need for smoking cessation programs to mitigate the associated health risks.

Diagnostic value of angiotensin-converting enzyme levels for assessing organ involvement in sarcoidosis: A retrospective single-centre study.

Inflammatory response and ACE2's potential role in acute primary angle-closure glaucoma during the Omicron epidemic of COVID-19.

ABSTRACTBackground and Objective:Sarcoidosis is a systemic granulomatous disease that primarily affects the lungs. Corticosteroids are the first-line therapy, but steroid resistance remains a major clinical challenge. This study evaluates baseline serum angiotensin-converting enzyme (sACE) levels as a potential biomarker for predicting steroid resistance in sarcoidosis.Methods:In this prospective single-centre study, 188 patients with biopsy-confirmed sarcoidosis had baseline sACE levels measured before corticosteroid initiation using the Kasahara colorimetric technique. Associations between sACE levels and treatment response were analysed using logistic regression and ROC analysis (SPSS v21; significance at P < 0.05).Results:The mean age of the cohort was 54 years, with 62% women. Common symptoms included cough, dyspnoea, fatigue, and arthralgia; hypercalcemia was seen in 11%. Elevated baseline sACE > 64 U/L was found in 41% of cases. ROC analysis yielded an (AUC) of 0.788 (95% CI: 0.685–0.891), with 83% sensitivity and 73% specificity for predicting steroid resistance. On multi-variate analysis, elevated sACE (P < 0.001), age > 54 years (P < 0.001), fatigue (P = 0.002), hypercalcemia (P = 0.019), and mediastinal lymph node involvement on CECT (P = 0.036) were independent predictors of poor steroid response.Conclusion:Elevated baseline sACE levels show potential as an adjunctive biomarker for identifying patients at risk of steroid resistance in sarcoidosis. However, given its moderate specificity and absence of longitudinal validation, sACE should be interpreted cautiously and in conjunction with clinical and radiological parameters. Multi-centre studies with longer follow-up are warranted to confirm these findings.

Granulomatous tubulointerstitial nephritis (TIN) is a rare histological entity detected in less than 1% of kidney biopsies1. It is caused by diverse etiological agents including drugs , infections , autoimmune diseases , tuberculosis, sarcoidosis and idiopathic. 46 yrs old lady had history of nephrotic Syndrome in 2006 and T2DM since 2011. She was evaluated for dry cough, low grade fever and uncontrolled diabetes mellitus in Oct 2024. Evaluation revealed hypercalcemia and advanced renal dysfunction, normal serum angiotensin converting enzyme (ACE) level , No M band, normal K:L ratio , normal Vit D level and intact parathyroid hormone (i PTH) level. CT chest showed multiple confluent nodules in lungs, mediastinal &amp; bilateral hilar lymphadenopathy. Ultrasonography showed normal size kidneys and fundus examination was normal. She underwent kidney biopsy and fibro optic bronchoscopy. Mycobacterium tuberculosis (MTB) GenXprt was negative. Native kidney biopsy showed the presence of multiple closely packed, non-necrotising, naked epithelioid cell granulomas with surrounding minimal lymphomononuclear cell infiltrate. Reticulin fibre rich granuloma kidney tissue and Romanowsky stain in lung tissue showing slipper shaped epitheloid cell granuloma suggest diagnosis of sarcoidosis. She was managed with steroids and showed good recovery of renal function. Steroids tappering started after 1 month. Renal sarcoidosis usually presents with nephrocalcinosis or renal calculi due to hypercalciuria, granulomatous renal involvement is rare. In our patient MTB polymerase chain reaction (PCR) was negative and serum ACE levels were also normal. In such a setting additional histology inputs like reticulin fibre rich granuloma and slipper shaped epithelioid cell granuloma suggested diagnosis of sarcoidosis.

Acute respiratory distress syndrome (ARDS) is a form of progressive hypoxemia that can be brought on by a variety of cardiorespiratory or systemic disorders, such as coronavirus disease 2019 (COVID-19). The binding of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus spike protein to the cell membrane is mediated through its binding to angiotensin-converting enzyme 2 (ACE2) receptors, resulting in viral entry, replication, and induction of a signaling cascade inducing pro-inflammatory responses that are linked to a higher mortality rate and the progression of ARDS, leading to multi-organ failure in these patients. We aimed to analyze the relationships between circulating gene expression levels of ACE2, Toll-like receptor 4 (TLR4), and interleukin-17 (IL-17) and the clinical severity of COVID-19, as well as the associated pathogenic conditions, in hospitalized patients. Sixty COVID-19 patients (34 mild/moderate COVID-19 and 26 COVID-19 with severe ARDS manifestation) and 60 healthy controls were included. The patient group was also subdivided according to outcomes into 32 recoveries and 28 deaths. ACE2, TLR4, and IL-17 levels were assessed by quantitative polymerase chain reaction (qPCR) in addition to all routine baseline laboratory investigations, including complete blood count (CBC) with differential analysis and the levels of C-reactive protein (CRP), ferritin, and d-dimer. ACE2, TLR4, and IL-17 serum expression levels were significantly higher in the COVID-19 group and subgroups and were correlated with different laboratory and clinical parameters. The serum expression levels of ACE2, TLR4, and IL-17 were accurate in differentiating between the patient groups and controls, with 86.7%, 91.7%, and 95.0% sensitivity and 96.7%, 98.3%, and 98.3% specificity, respectively, and correlated with more severe disease courses in COVID-19 patients. Higher levels are associated with overwhelmingly distressing outcomes. Our results allow us to conclude that increased circulating gene expression levels of ACE2, TLR4, and IL-17 are important in assessing the severity of COVID-19. Consequently, targeting these biomarkers may offer additional therapeutic options for COVID-19 patients in the future.