Introduction

Pulmonary mucormycosis is a potential complication in patients with diabetic ketoacidosis. Isolation of filamentous fungus from bronchoscopy specimens of this population may prompt clinicians to include pulmonary mucormycosis in their differential diagnoses and initiate high-dose intravenous liposomal amphotericin (>5 mg/kg/day). Amphotericin is an expensive therapy and is frequently associated with adverse effects such as nephrotoxicity, phlebitis, and acute febrile reaction. We encountered a case in which pulmonary aspergillosis rather than mucormycosis was diagnosed in a patient with diabetic ketoacidosis.

Method

A 36-year-old female with history of type 1 diabetes was admitted to an intensive care unit due to increased work of breathing and decreased Glasgow coma scale (14). She presented with a temperature of 33.4 Celsius, glucose 39 mmol/L, beta-hydroxybutyrate 11.4 mmol/L, and blood gas of pH 6.94, bicarbonate 5 mmol/L, carbon dioxide partial pressure 24, and lactate 1.6 mmol/L. Computed tomography showed extensive parenchymal disease with reticulation and air space opacity and well circumscribed nodules distributed throughout the lungs (largest 14 mm). (Figure 1 https://drive.google.com/file/d/16_Tw4Uoa2FbavqeM5_u7IomSOTeoMOo0/view?usp=sharing). Bronchoalveolar lavage specimens were sent to the microbiology laboratory, where heavy growth of filamentous fungus was identified on culture plates (Figure 2 https://drive.google.com/file/d/1CSIng6R2YYDfAt9evfVnVm6zvLspKvvV/view?usp=sharing).

Results

The fungus isolates were examined under 400x magnification with lactophenol blue stain and identified as Aspergillus nigers (Figure 3 https://drive.google.com/file/d/1Qjd-CCyIusivBVLfX0uTc2GsijpMp0oV/view?usp=sharing) and Aspergillus flavus (Figure 4 https://drive.google.com/file/d/1-4nY7_RInykv-HWUXuGF-IZ-8VT-E_ra/view?usp=sharing). The patient was given 200 mg intravenous voriconazole every 12 hours, a first-line therapy for aspergillosis. She achieved clinical improvement and was later discharged home.

Conclusion

Like pulmonary mucormycosis, pulmonary aspergillosis could happen in patients with diabetic ketoacidosis and should be kept in the differentials. The first-choice therapy differs for pulmonary mucormycosis and aspergillosis.

Background:
E-cigarette or vaping-associated lung injury (EVALI) presents with heterogeneous histopathological findings, yet systematic analyses remain limited. Although case reports have documented patterns such as diffuse alveolar damage (DAD) and organizing pneumonia, no prior meta-analysis has examined these findings at the individual patient level or explored how injury patterns differ by vaping substance.

Methods:

This individual patient data (IPD) meta-analysis systematically evaluated histopathological features in e-cigarette or vaping product use-associated lung injury (EVALI), synthesizing evidence from 10 studies comprising 38 cases. Following PRISMA-IPD guidelines, we searched MEDLINE, Embase, PubMed, Scopus, and conference proceedings without restrictions. Eligible studies reported lung biopsy/autopsy findings in CDC-defined EVALI cases. Composite variables were created for inflammation severity (none/mild/moderate-severe), macrophage/lipid abnormalities (present/absent), and dominant pathological patterns (e.g., diffuse alveolar damage [DAD], organizing pneumonia).

Results:
Acute fibrinous pneumonitis (31.6%), organizing pneumonia (23.7%), and diffuse alveolar damage (13.2%) were the most common histopathological patterns. Lipid-laden macrophages were detected in 21.1% of cases. Vape type significantly predicted macrophage/lipid abnormalities (χ²(3)=14.97, p=.002), with the highest prevalence among nicotine-only users (62.5%). In contrast, THC-only users showed a markedly lower prevalence (7.1%). No significant associations were observed between macrophage abnormalities and age, sex, smoking history, vaping duration, or immune cell profiles in bronchoalveolar lavage fluid (p > .05).

Conclusion:
This IPD meta-analysis highlights acute fibrinous pneumonitis as the predominant pattern in EVALI and suggests that nicotine-based products may be more strongly associated with lipid-related macrophage abnormalities than THC products. These findings support the hypothesis of substance-specific lung injury mechanisms and underscore the need for tailored diagnostic criteria and regulatory oversight.

Introduction:
Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder characterized by repetitive upper airway obstruction during sleep, resulting in intermittent hypoxia, hypercapnia, and marked fluctuations in intrathoracic pressure. These physiological disturbances have systemic consequences and are increasingly recognized for their impact on cerebral hemodynamics and intracranial pressure (ICP). Understanding this relationship is particularly critical in patients with coexisting neurological disorders.

Objective:
This systematic review aims to synthesize current evidence on the bidirectional relationship between OSA and elevated ICP, with an emphasis on underlying mechanisms, clinical implications, and therapeutic considerations across conditions such as idiopathic intracranial hypertension (IIH), traumatic brain injury (TBI), and hydrocephalus.

Methods:
A comprehensive literature search was conducted in accordance with PRISMA guidelines across PubMed, Scopus, Web of Science, and Google Scholar. Search terms included combinations of Medical Subject Headings (MeSH) and Boolean operators, with no date restrictions. Thirty-five studies met the inclusion criteria, covering both clinical and experimental data.

Findings:
Evidence from the reviewed studies suggests that the cyclical hypoxia and intrathoracic pressure changes in OSA may lead to transient elevations in ICP and disrupt cerebrospinal fluid (CSF) dynamics. These effects may exacerbate symptoms or disease progression in patients with underlying intracranial pathology. While CPAP therapy remains the standard of care for OSA, its impact on ICP is variable, with some reports indicating a benefit and others suggesting a potential elevation of ICP, particularly in specific patient populations.

Conclusion:
There is growing support for a complex and potentially bidirectional interaction between OSA and ICP. However, inconsistencies across study methodologies and patient cohorts limit the ability to draw definitive conclusions. Future research should focus on standardized assessment protocols and targeted investigations to better understand how OSA management may influence ICP regulation and neurological outcomes.

Objective: To analyze the burden due to asthma and its changes in China from 1990 to 2023.

Methods: Using data from the Global Burden of Disease 2023 (GBD 2023) study, we analysed six key indicators: the mortality, prevalence, incidence, disability-adjusted life years, years lived with disability, and years of life lost. Age-standardized rates were analysed using the global age structure as a reference. Joinpoint regression was used to assess the annual percentage change and average annual percentage change.

Results: In 2023, 45,991,602 prevalent cases, with 8,028,745 incidence cases and 23,699 deaths due to asthma, were reported from China. The number crude rates of the prevalence, mortality, disability-adjusted life years, and years lived with disability significantly increased in 2023 compared with 1990. The age-standardized rates per 100,000 were 3066.76 for prevalence (+5.65% from 1990), 717.95 for incidence (-2.18%), 1.11 for mortality (-53.36%), 140.90 for disability-adjusted life years (-14.77%), 120.42 for years lived with disability (5.81%), and 20.47 for years of life lost (-31.40%). The burden of asthma was higher in males than in females during 1990-2023. In 2023, the incidence rate was the highest among individuals under 10 years of age. The prevalence rate, mortality rate, disability-adjusted life years rate, and years of life lost rate were the highest among the population aged 95 and over. The years lived with disability rate was the highest among those aged 70-74.

Conclusion: Between 1990 and 2023, China's asthma burden showed age- and sex-specific trends: crude rates for prevalence, mortality, and disability increased, but age-standardized rates for mortality, disability-adjusted life years, and years of life lost declined. Males faced higher burdens than females. Key age groups included: under-10s (highest incidence), ≥95-year-olds (highest prevalence, mortality, disability-adjusted life years, years of life lost), and 70–74-year-olds (highest years lived with disability). Targeted interventions by age and sex are needed to address these disparities.

Introduction/Aim: We previously reported pulmonary arterial remodelling and active endothelial to mesenchymal transition (EndMT) in smokers and patients with early COPD. In this study, we aimed to evaluate the role of different drivers of EndMT.

Methods: Immunohistochemical staining for EndMT drivers, TGF-β1, pSMAD-2/3, SMAD-7, and β-catenin was performed on surgically resected lung tissue from 46 subjects. Twelve were non-smoker controls (NCs), six were normal lung function smokers (NLFS), nine were patients with small-airway diseases (SADs), nine were mild-moderate COPD-current smokers (COPD-CSs), and ten were COPD-ex-smokers (COPD-ESs). Histopathological measurements were taken using Image ProPlus software V7.0.

Results: We observed lower levels of total TGF-β1 (p<0.05) in all smoking groups than in the non-smoking control (NC). Across arterial sizes, smoking groups exhibited significantly higher pSMAD-2/3 and SMAD-7 expression (p <0.05) in total and individual layers than in the NC group. The ratio of SAMD-7 to pSMAD-2/3 was higher in COPD patients compared to NC patients. Total β-catenin expression was significantly higher in smoking groups across arterial sizes (p <0.05), except for COPD-ES and NLFS groups in small and medium arteries, respectively. Increased total β-catenin was positively correlated with total S100A4 in small and medium arteries (r= 0.35, 0.50; p=0.02, 0.01, respectively), with vimentin in medium arteries (r=0.42, p=0.07), and with arterial thickness of medium and large arteries (r= 0.34, 0.41, p=0.02, 0.01, respectively).

Conclusion: This is the first study uncovering an active endothelial SMAD pathway independent of TGF-β1 in smokers, SAD, and COPD patients. Increased expression of β-catenin indicates its potential interaction with the SMAD pathway, warranting further research to identify the deviation from this classical pathway.

The KRAS oncogene (EC 3.6.5.2) is the most frequently mutated gene in non-small cell lung cancer (NSCLC), being present in approximately 25–30% of cases. Among these alterations, the KRAS p.G12C mutation is particularly relevant, occurring in ~12–14% of NSCLC and strongly associated with smoking. This mutation impairs GTP hydrolysis and promotes constitutive activation of the protein, driving uncontrolled cell proliferation. Tumors harboring this mutation usually show poor response to EGFR-targeted therapies, although they may benefit from immunotherapy. More recently, covalent inhibitors have shown clinical efficacy by specifically targeting KRAS G12C; however, both primary and acquired resistance remain significant challenges, highlighting the need for novel therapeutic strategies. In this context, a library of 249 alkaloids was constructed and subjected to virtual screening against the oncogenic KRAS G12C variant (PDB: 4NMM, Homo sapiens). Following the docking studies, their toxicity and pharmacokinetic properties were predicted in silico using the StopTox platform. Protein preparation included validation of the docking protocol through re-docking of the co-crystallized ligand, 5'-O-[(S)-{[(S)-2-(acetylamino)ethoxyphosphoryl]oxy}(hydroxy)phosphoryl]guanosine. Docking simulations were performed in YASARA using the AutoDock Vina engine. The results identified four alkaloids with binding energies superior to the crystallographic control (-8.40 kcal/mol): Oxoisocoridine (-8.99 kcal/mol), Aporglauquine (-8.67 kcal/mol), Oxyaporphine (-8.60 kcal/mol), and Oxyisocoridine (-8.45 kcal/mol). Toxicity predictions indicated that all candidates are non-toxic orally, non-irritant to the eyes, non-sensitizing, and non-corrosive to the skin, according to computational models. Overall, these findings suggest that alkaloids represent promising scaffolds for KRAS G12C inhibition, combining high predicted binding affinities with a favorable toxicity profile. Nonetheless, experimental validation is essential to confirm their potential as anticancer candidates.

OBESITY AND ANTIVIRAL OUTCOMES: IS NIRMATRELVIR–RITONAVIR EFFECTIVE IN REDUCING HOSPITALIZATION IN OBESE PATIENTS WITH COVID-19?

We conducted a systematic review and meta-analysis entitled "Obesity and Antiviral Outcomes: Is Nirmatrelvir–Ritonavir Effective in Reducing Hospitalization in Obese Patients with COVID-19?"
We compared nirmatrelvir–ritonavir with placebo to assess its impact on hospitalization rates in obese patients diagnosed with COVID-19. Three studies met the inclusion criteria, all comparing nirmatrelvir–ritonavir in outpatients with PCR-confirmed COVID-19 and obesity (body mass index >25 kg/m²) versus placebo.

The primary endpoint was the hospitalization rate. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated. Our analysis showed that nirmatrelvir–ritonavir did not significantly reduce hospitalization rates in obese patients with COVID-19 (OR 0.84; 95% CI 0.57–1.25; p=0.39). Given the high global prevalence of obesity and its role as a risk factor for severe COVID-19, further research into tailored therapeutic strategies for this vulnerable population is needed. Limitations include reduced data availability for obese patients, inclusion of only three observational studies, and potential heterogeneity.
References

1. Aggarwal NR, Molina KC, Beaty LE, Bennett TD, Roe CC, Blake SN, et al. Real-world use of nirmatrelvir–ritonavir in outpatients with COVID-19 during the era of Omicron variants including BA.4 and BA.5 in Colorado, USA: a retrospective cohort study. Lancet Infect Dis. 2023. doi:10.1016/S1473-3099(23)00180-7.

2. Scaglione F, Gentile I, Sberna G, Cicolini G, Castagna A. Impact of oral early antiviral therapies for mild–moderate COVID-19 in the outpatient setting during Omicron era: a pharmacoeconomic analysis. Clin Drug Investig. 2024;44(2):99-108. doi:10.1007/s40261-023-01287-4.

3. Wu MY, Pan YH, Hsu YL, Chen YH, Lin YY, Hsu CK. Association between nirmatrelvir plus ritonavir and the outcomes of non-hospitalized obese patients with COVID-19. J Microbiol Immunol Infect. 2023. doi:10.1016/j.jmii.2023.06.004.

Introduction

Recent clinical-scientific research finding demonstrates that cosmetic surgery can lead to severe complications, including suicides, and is associated with the surgical concepts of today's most commonly used techniques, marking it as the first report in medical literature. The pictorial documentation and narrative presentation of severe cosmetic surgical complications are detailed.

Methods

A case series study was conducted to provide pictorial documentation of severe cosmetic complications related to labia minora from currently used surgical interventions.

Results

Severe complications from cosmetic surgery appeared in various forms and were primarily associated with labial amputations (labioplasty, trimmings, linear, and other marketing terms) affecting the labial trunk, clitoral prepuce, and frenulum. Predominantly, labial over-resection was the leading cause of these adverse, symptomatic surgical outcomes. Labia minora central wedge resection is the second most common surgical intervention. It causes severe complications and results in an unnatural anatomical appearance. This procedure involves V-shaped resections from the free edge to the base of the labial tissues. Such a technique includes removing vital anatomical structures of the neurovascular bundle and its anastomosis, leading to symptoms associated with the disruption of nerves and vessels.
The delamination of the labia minora technique creates a monolithic structure that consists of the clitoral prepuce, clitoral frenulum, and labia minora trunk. Additionally, this surgical technique creates labial eversion, fusing the inner surface of the clitoral prepuce with the clitoral glans. This can lead to persistent clitoral compression with engorgement and can result in clitoral atrophy (an irreversible condition). The concept of this surgical intervention is poorly developed.

Conclusions

Using labium minus reduction techniques is linked to serious complications because of underdeveloped surgical concepts. A new approach to surgical interventions should be created to reduce or eliminate complications related to cosmetic surgery.

Introduction:

Although opioids are often prescribed during surgery, an increasing number of patients are requesting opioid-free surgery (OFS). Perioperative care is often protocol-driven and may not account for individualized preoperative directives. Consequently, patient requests to avoid opioids are not always consistently communicated across the surgical care team. Despite enhanced recovery after surgery (ERAS) protocols that use a multimodal approach and regional anesthesia, completely avoiding opioids to meet patient requests is not consistently achieved. This study aimed to assess the feasibility and outcomes of the Patient-Controlled Opioid-Free Surgical Pathway (PCOFSP) in fulfilling patients’ requests for opioid-free surgery.

Methods:

The PCOFSP is based on a multimodal approach, regional anesthesia, and the use of complementary techniques. It begins with proper patient identification, education, and coordination among the care team. The pathway was initiated in May 2024 using a Plan-Do-Study-Act framework. Descriptive statistics were used to summarize demographics and outcomes. Continuous variables are reported as medians with interquartile ranges (IQRs), and categorical variables are reported as frequencies and percentages.

Results:

Of 1,175 patients screened, 16.1% requested OFS. Median age was 66 years (IQR of 58–72); 59% were male. Overall, 74.1% underwent OFS, 18.5% received opioids intraoperatively or in the (P) ACU, and 7.4% withdrew. Success was highest in plastic (100%) and orthopedic surgery (82.4%) and lowest in urology (67.8%). Median length of stay was 1.1 days (IQR of 0.6–1.5). Complementary techniques included aromatherapy (n=157), nanotechnology patches (n=15), auriculotherapy and mindful breathing (n=4), and hypnosis or music therapy (n=2). Five patients re-enrolled for a second surgery.

Conclusion:

The PCOFSP enabled 74% of patients to undergo OFS. Our data suggest that, by integrating regional anesthesia, multimodal analgesics, complementary therapies, and effective communication, the PCOFSP allows patients to successfully undergo OFS.

Background: Placenta accreta spectrum (PAS) disorders are severe obstetric complications associated with abnormal adherence of the placenta to the uterine wall, often leading to massive peripartum hemorrhage and maternal morbidity or mortality. Standard management of PAS involves cesarean hysterectomy, which carries a high risk of intraoperative blood loss and transfusion-related complications. Fibrinogen, a critical coagulation factor, is among the first to reach critical low levels during massive bleeding, and early supplementation may improve hemostatic control. ROTEM-guided studies have shown that fibrinogen levels correlate with clot firmness and that early correction can reduce transfusion requirements. However, evidence regarding the effectiveness of prophylactic fibrinogen administration in obstetric hemorrhage, especially in PAS disorders, remains limited and inconclusive. Methods: A double-blind randomized controlled trial was initiated at AIIMS, New Delhi. Patients with confirmed PAS diagnosis (n=14 in year one) were randomized into two groups to receive either 2g fibrinogen (n=7) or placebo (n=7) at the time of cord clamping. Blood samples were collected at baseline, 15 min post-drug, every 500 ml of blood loss, and 24 hours post-administration to assess hemogram, coagulation profile, and ROTEM parameters. Hemodynamic, intraoperative blood loss, and transfusion data were recorded. Data were analysed using t-tests with p<0.05 as the significance threshold. Results: The fibrinogen group had significantly lower intraoperative blood loss (1950 ± 340.3 ml vs 2342.8 ± 325.9 ml; p=0.047) and transfused pRBC volume (464.3 ± 172.5 ml vs 892.9 ± 349.3 ml; p=0.013) compared to placebo. ROTEM parameters showed significantly improved clot firmness (MCF) and fibrinogen levels from sample 2 to 5 in the fibrinogen group. No significant differences were observed at 24h post-administration. No thromboembolic events or adverse effects were reported in either group. Conclusion: Pre-emptive administration of 2g fibrinogen in PAS patients reduces intraoperative blood loss and transfusion requirement without increasing complications. Findings suggest fibrinogen may be a valuable adjunct in managing PAS-associated hemorrhage and warrant further validation in a larger cohort.