Comprehensive Clinical Evaluation Research Articles

Bridging dermatology and hematology: a case of lepromatous leprosy with bone marrow involvement and pancytopenia.

Leprosy, caused by Mycobacterium leprae (M. leprae), primarily manifestswith cutaneous and peripheral nerve involvement. Systemic involvement, particularly in the bone marrow, is exceedingly rare. This report presents a case of lepromatous leprosy with bone marrow involvement, emphasizing the systemic nature of the disease and the importance of comprehensive diagnostic and management approaches. We aim to present a case of lepromatous leprosy with bone marrow involvement, detailing the clinical presentation, diagnostic evaluation, and management approach. A 65-year-old male with lepromatous leprosy and severe erythema nodosum leprosum developed pancytopenia. After undergoing comprehensive clinical evaluation, including history taking, physical examination, and laboratory investigations, bone marrow examination and molecular diagnostics using polymerase chain reaction (PCR) were performed to confirm the presence of M. leprae as an etiology for his pancytopenia. The bone marrow aspirate revealed hypercellularity with erythropoiesis and thrombopoiesis within normal limits. Foamy histiocytes with erythrophagocytosis were observed, along with the presence of M. leprae on Modified Ziehl-Neelsen stain. Molecular analysis confirmed M. leprae DNA in the bone marrow aspirate. Treatment with multi-drug therapy (MDT) and thalidomide resulted in normalization of blood counts and healing of skin lesions. This case underscores the systemic nature of leprosy and the rarity of bone marrow involvement, highlighting the importance of thorough evaluation in cases of persistent symptoms. Comprehensive diagnostic approaches, including bone marrow examination and molecular diagnostics, are essential for accurate diagnosis and timely initiation of appropriate treatment, ultimately improving patient outcomes and minimizing disease complications.

Psychiatric Diagnosis: A Clinical Guide to Navigating Diagnostic Pluralism.

The controversies surrounding the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases have generated significant debate across the psy-sciences. This debate has been further fueled by the launch of the Research Domain Criteria as a framework to facilitate advances in neuroscientific research, a renewed emphasis on dimensional models of psychopathology, currently exemplified by the Hierarchical Taxonomy of Psychopathology, and development of the Psychodynamic Diagnostic Manual by the psychodynamic community. In this article, we provide a clinical overview of recent debates surrounding categorical and dimensional approaches to psychiatric diagnosis, offer a critical assessment of proposed alternatives, and discuss how clinicians can navigate a plurality of diagnostic frameworks. Our discussion emphasizes that diagnostic frameworks need to be contextualized within the process of a comprehensive clinical evaluation, and their advantages and disadvantages should be understood in relationship to the theoretical orientations and practical needs of clinicians.

Longitudinal evaluation of polyneuropathy in Parkinson's disease.

Increasing evidence indicates a higher prevalence of polyneuropathy (PNP) in Parkinson's disease (PD). However, the involvement of large fiber neuropathy in PD still remains poorly understood. Given the lack of longitudinal data, we investigated the course of PNP associated with PD. In total, 41 PD patients underwent comprehensive clinical evaluation including motor and non-motor assessments as well as nerve conduction studies at baseline and at 2years of follow-up. The definition of PNP was based on electrophysiological standard criteria. Common causes of PNP were excluded. At baseline, PNP was diagnosed in 65.85% of PD patients via electroneurography. Patients with PNP presented with higher age (p = 0.019) and PD motor symptom severity (UPDRS III; p < 0.001). Over the course of 2years, PNP deteriorated in 21.95% of cases, and 26.83% remained without PNP. Deterioration of nerve amplitude was most prevalent in the median sensory nerve affecting 57.58% of all PD cases with an overall reduction of median sensory nerve amplitude of 45.0%. With regard to PD phenotype, PNP progression was observed in 33.33% of the tremor dominant and 23.81% of the postural instability/gait difficulties subtype. Decrease of sural nerve amplitude correlated with lower quality of life (PDQ-39, p = 0.037) and worse cognitive status at baseline (MoCA, p = 0.042). The study confirms the high PNP rate in PD, and demonstrates a significant electrophysiological progression also involving nerves of the upper extremities. Longitudinal studies with larger cohorts are urgently needed and should elucidate the link between PD and PNP with the underlying pathomechanisms.

Contribution of testosterone and estradiol in sexual dimorphism of early-onset Parkinson's disease.

Early-onset Parkinson's disease (EOPD) occurs during the fertile life, when circulating neuroactive sex hormones might enhance the sexual dimorphism of the disease. Here, we aimed to examine how sex hormones can contribute to sex differences in EOPD patients. A cohort of 34 EOPD patients, 20 males and 14 females, underwent comprehensive clinical evaluation of motor and non-motor disturbances. Blood levels of estradiol, total testosterone, follicle-stimulating hormone, and luteinizing hormone were measured in all patients and correlated to clinical features. We found that female patients exhibited greater non-motor symptoms and a relatively higher rate of dystonia than males. In females, lower estradiol levels accounted for higher MDS-UPDRS-II and III scores and more frequent motor complications, while lower testosterone levels were associated with a major occurrence of dystonia. In male patients, no significant correlations emerged. In conclusion, this study highlighted the relevance of sex hormone levels in the sexual dimorphism and unique phenotype of EOPD.

Structural changes and contractility in muscle assessed by magnetic resonance imaging in individuals with ryanodine receptor 1-related rhabdomyolysis or myalgia.

Ryanodine receptor 1 (RYR1)-related myopathies associated with variants in the RYR1 gene present with a wide range of symptoms and severity. Two of the milder phenotypes associated with dominant pathogenic variants in RYR1 are rhabdomyolysis and myalgia. Only a few studies have investigated the muscle function and structure of individuals with RYR1-related rhabdomyolysis/myalgia objectively, showing inconsistent results. This study aimed to describe structural changes and contractility of muscles in individuals with RYR1-related rhabdomyolysis/myalgia. We investigated 15 individuals with dominant variants in the RYR1-gene and compared them with 15 age-, sex-, and body mass index (BMI)-matched controls using MRI, stationary isokinetic dynamometry, and comprehensive clinical evaluation. No significant differences were found between individuals with RYR1-related rhabdomyolysis/myalgia and healthy controls in peak torque, fat fraction, cross-sectional area, contractile cross-sectional area, or contractility (p > .05) in muscles of the lower back (MRI data only), thigh, or calf. On clinical examination, three individuals exhibited weakness in hip or back extension on the Medical Research Council (MRC) test and eight had muscle hypertrophy. Individuals with weakness were not hypertrophic. Most individuals with RYR1-related rhabdomyolysis/myalgia have close to normal strength, and normal fat fraction and contractility of muscles, and therefore constitute a mild phenotype of RYR1-related myopathies.

Frequency of Atypical AVNRT in Patients Presenting with Narrow Complex Tachycardia

ABSTRACT Objective: To determine the frequency of atypical AVNRT in patients presenting with Narrow Complex Tachycardia. Study Design: Descriptive Cross Sectional Place and Duration of Study: Department of Cardiology, MTI-Hayatabad Medical Complex, Peshawar, from March, 2021 to March, 2022. Methodology: Ninety-three patients of either aged 30 to 80 years diagnosed with narrow complex tachycardia by consultant cardiac electrophysiologist on ECG showing QRS duration of less than 120 milliseconds were included in this study. Patients were managed as per standard protocol which included comprehensive clinical evaluation such as patient history, physical examination and invasive electrophysiological study for the diagnosis and characterization of atypical Atrioventricular Nodal Reentrant Tachycardia (AVNRT). Results: A total of ninety-three patients were studied with mean age of 43.08 years (SD = 9.07). Among the participants, 58.1% were male, while 41.9% were female. Majority of patients had Slow-Fast AVNRT (7.5%) followed by Fast-Slow AVNRT (3.2%), and Slow-Slow AVNRT in 2.2% patients. Conclusion: This study underscored the importance of gender-specific variations in the prevalence of different AVNRT types and highlighted the impact of gender as a potential influencing factor in the manifestation of specific types of AVNRT within the study population.

Ulcerated nodular swelling in an immunocompetent child.

The presented case of tumor-like LV serves as a noteworthy illustration of the diverse clinical manifestations of cutaneous tuberculosis. The rarity of such lesions emphasizes the importance of considering tuberculosis particularly in regions with a high prevalence of the disease. The diagnostic challenge underscores need for a comprehensive clinical and histopathological evaluation to differentiate it from other dermatological conditions such as fixed cutaneous sporotrichosis, phaeohyphomycosis and botryomycosis among others.

Cross-linked Sodium Hyaluronate Gel with PLLA-b-PEG Microsphere for Facial Contouring in Chinese: A Retrospective Study.

In Asia, the demand for cosmetic facial treatments has surged due to technological advancements, increased social acceptability, and affordability. Poly-L-lactic acid (PLLA) fillers, known for their biocompatibility and biodegradability, have emerged as a popular choice for facial contouring, yet studies specifically addressing their use in Asian populations are scarce. This retrospective study examined 30 Chinese patients who underwent facial contouring with PLLA fillers, focusing on product composition, injection techniques, and safety measures. A comprehensive clinical evaluation was performed, including the Global Aesthetic Improvement Scale (GAIS) and Global Impression of Change Scale (GICS) for effectiveness and patient satisfaction, respectively. No significant difference in GAIS scores was observed between injectors and blinded evaluators over a 12-month period, indicating consistent effectiveness. Patient satisfaction remained high, with GICS scores reflecting positive outcomes. The safety profile was favorable, with no serious adverse events reported. The study highlighted the importance of anatomical knowledge to avoid complications, particularly in areas prone to blindness. PLLA fillers offer a safe, effective option for facial contour correction in the Asian population, achieving high patient satisfaction and maintaining results over time. The study underscores the need for tailored approaches in cosmetic procedures for Asians, considering their unique facial structures and aesthetic goals. Further research with larger, multicenter cohorts is recommended to validate these findings and explore long-term effects. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical characteristics and risk factors for mortality in pneumonia-associated acute respiratory distress syndrome patients: a single center retrospective cohort study

BackgroundPathogenic diversity may have contributed to the high mortality of pneumonia-associated acute respiratory distress syndrome (p-ARDS). Metagenomics next-generation sequencing (mNGS) serves as a valuable diagnostic tool for early pathogen identification. However, its clinical utility in p-ARDS remains understudied. There are still limited researches on the etiology, clinical characteristics and risk factors for 28-day mortality in p-ARDS patients.MethodsA single center retrospective cohort study of 75 p-ARDS patients was conducted. Patients were categorized into survival and deceased groups based on their 28-day outcomes. A comprehensive clinical evaluation was conducted, including baseline characteristics, laboratory indicators, outcomes and pathogen identification by mNGS and traditional microbiological testing. We then evaluated the diagnostic value of mNGS and identified clinical characteristics and risk factors for 28-day mortality in p-ARDS.ResultThe overall ICU mortality was 26.67%, and the 28-day mortality was 57.33%, with 32 cases (42.67%) in the survival group, and 43 cases (57.33%) in the deceased group. Patients in the deceased group were older than those in the survival group (68(59,73) years vs. 59(44,67) years, P=0.04). The average lengths of ICU and hospital stay were 9(5,13) days and 14(7,21) days, respectively. The survival group had longer lengths of ICU and hospital stay (ICU: 11(7,17) days and hospital: 17(9,27) days) compared to the deceased group (ICU: 8(4,11) days and hospital: 12(6,19) days) (P&amp;lt;0.05). Survival patients exhibited lower Acute Physiology and Chronic Health Evaluation (APACHE) II score on the 3rd and 7th days, higher lymphocyte counts, higher CD3+ and CD8+ T cell counts compared to deceased patients (P&amp;lt;0.05). Multivariate logistic regression analysis identified age, APACHE II scores on 3rd and 7th days, CD8+ T cell count and length of ICU as independent risk factors for 28-day mortality in p-ARDS patients. mNGS demonstrated a significantly higher overall pathogen detection rate (70/75, 93.33%) compared to the traditional method (50/75, 66.67%, P=0.022). The average turnaround time (TAT) for mNGS was significantly shorter at 1(1,1) day compared to 4(3,5) days for the traditional method (P&amp;lt;0.001).ConclusionMetagenome next-generation sequencing can be used as a valuable tool for identifying pathogens in p-ARDS, reducing diagnostic time and improving accuracy. Early application of mNGS alongside traditional methods is recommended for p-ARDS. Furthermore, older age, higher APACHE II scores, lower lymphocyte counts and lymphocyte subset counts were associated with increased mortality in p-ARDS patients, highlighting the importance of timely assessment of immune status and disease severity, especially in elderly.

Clinical characteristics and risk factors for mortality in pneumonia-associated acute respiratory distress syndrome patients: a single center retrospective cohort study.

Pathogenic diversity may have contributed to the high mortality of pneumonia-associated acute respiratory distress syndrome (p-ARDS). Metagenomics next-generation sequencing (mNGS) serves as a valuable diagnostic tool for early pathogen identification. However, its clinical utility in p-ARDS remains understudied. There are still limited researches on the etiology, clinical characteristics and risk factors for 28-day mortality in p-ARDS patients. A single center retrospective cohort study of 75 p-ARDS patients was conducted. Patients were categorized into survival and deceased groups based on their 28-day outcomes. A comprehensive clinical evaluation was conducted, including baseline characteristics, laboratory indicators, outcomes and pathogen identification by mNGS and traditional microbiological testing. We then evaluated the diagnostic value of mNGS and identified clinical characteristics and risk factors for 28-day mortality in p-ARDS. The overall ICU mortality was 26.67%, and the 28-day mortality was 57.33%, with 32 cases (42.67%) in the survival group, and 43 cases (57.33%) in the deceased group. Patients in the deceased group were older than those in the survival group (68(59,73) years vs. 59(44,67) years, P=0.04). The average lengths of ICU and hospital stay were 9(5,13) days and 14(7,21) days, respectively. The survival group had longer lengths of ICU and hospital stay (ICU: 11(7,17) days and hospital: 17(9,27) days) compared to the deceased group (ICU: 8(4,11) days and hospital: 12(6,19) days) (P<0.05). Survival patients exhibited lower Acute Physiology and Chronic Health Evaluation (APACHE) II score on the 3rd and 7th days, higher lymphocyte counts, higher CD3+ and CD8+ T cell counts compared to deceased patients (P<0.05). Multivariate logistic regression analysis identified age, APACHE II scores on 3rd and 7th days, CD8+ T cell count and length of ICU as independent risk factors for 28-day mortality in p-ARDS patients. mNGS demonstrated a significantly higher overall pathogen detection rate (70/75, 93.33%) compared to the traditional method (50/75, 66.67%, P=0.022). The average turnaround time (TAT) for mNGS was significantly shorter at 1(1,1) day compared to 4(3,5) days for the traditional method (P<0.001). Metagenome next-generation sequencing can be used as a valuable tool for identifying pathogens in p-ARDS, reducing diagnostic time and improving accuracy. Early application of mNGS alongside traditional methods is recommended for p-ARDS. Furthermore, older age, higher APACHE II scores, lower lymphocyte counts and lymphocyte subset counts were associated with increased mortality in p-ARDS patients, highlighting the importance of timely assessment of immune status and disease severity, especially in elderly.

Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations. We recruited 50 SLE patients (1 male to 12.5 females, aged 20-80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin. Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (p = .0143); furthermore, they were more likely to have a history of hypocomplementemia (p = .0058) and to be treated with cyclosporine A (p = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN. This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.

Corrected QT interval and QT dispersion in temporal lobe epilepsy in children and adolescent

&lt;b&gt;Aim&lt;/b&gt;: The purpose of this research was to contrast (heart-rate corrected QT interval) QTc, and (QT dispersion) QTd intervals in individuals with (temporal lobe epilepsy) TLE and those without TLE using a standard 12-lead electrocardiogram.&lt;br /&gt; &lt;b&gt;Patients &amp;amp; methods&lt;/b&gt;: This cross-sectional research was undertaken on 100 cases aged 10 to 20 diagnosed with epilepsy in accordance with 2017 ILAE criteria. The patients’ informed written permission was acquired. In our study, we included 100 cases: 50 with TLE and 50 with non-TLE verified by seizure semiology. All patients were subjected to a comprehensive history, clinical examination (heart rate, pulse, and blood pressure), and clinical evaluation, which included a comprehensive epilepsy history. On the basis of neurology service documents or the initial publication of the international classification of diseases, 9&lt;sup&gt;th&lt;/sup&gt; revision (ICD9) diagnostic or 10&lt;sup&gt;th&lt;/sup&gt; revision (ICD10) codes for epilepsy, diagnostic age for epilepsy was calculated.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;The mean QT interval in group I was 418.30±25.48 ms while that of group II was 406.20±27.63 ms, the mean QTc of group I was 513.60±61.94 ms and was 488.70±50.65 in group II. The calculated QTd was with a mean of 57.60±25.05 ms while that of group II was 43.60±31.89 ms. It means that the QT interval, QTc, and QTd values were considerably greater in the group I (temporal epilepsy) contrasted with group II (non-temporal epilepsy); (p=0.025, 0.030, and 0.016, respectively). The mean QT, QTc, and QTd values for FE were 409.20±20.80, 500.70±55.60, and 52.60±29.70 ms, respectively. QT, QTc, and QTd mean values for patients with widespread epilepsy were 412.00±25.60, 505.00±68.60, and 46.20±28.70 ms. QT, QTc, and QTd interval were insignificantly different between focal and generalized epilepsy. The longer an illness progresses, the longer the QT and QTc intervals, as there was a substantial positive correlation among illness’s course and QT interval (r=0.391, p&amp;lt;0.001) and QTc interval (r=0.289, p=0.011), but there was no noticeable impact on QTd due to the illness’s duration, as we found an insignificant correlation among duration of illness and QTC and QTd.&lt;br /&gt; &lt;b&gt;Conclusions: &lt;/b&gt;Our findings indicate that; QTc interval and QTd are longer in epilepsy cases more among TLE cases contrasted with non-TLE. Since there was no distinction among different epilepsy types (focal and generalized).

Catalyzing precision: unraveling the diagnostic conundrum of tunisian familial hypophosphatasia case through integrative clinical and molecular approaches.

Familial Hypophosphatasia presents a complex diagnostic challenge due to its wide-ranging clinical manifestations and genetic heterogeneity. This study aims to elucidate the molecular underpinnings of familial Hypophosphatasia within a Tunisian family harboring a rare c.896 T > C mutation in the ALPL gene, offering insights into genotype-phenotype correlations and potential therapeutic avenues. The study employs a comprehensive approach, integrating biochemical examination, genetic analysis, structural modeling, and functional insights to unravel the impact of this rare mutation. Genetic investigation revealed the presence of the p.Leu299Pro mutation within the ALPL gene in affected family members. This mutation is strategically positioned in proximity to both the catalytic site and the metal-binding domain, suggesting potential functional consequences. Homology modeling techniques were employed to predict the 3D structure of TNSALP, providing insights into the structural context of the mutation. Our findings suggest that the mutation may induce conformational changes in the vicinity of the catalytic site and metal-binding domain, potentially affecting substrate recognition and catalytic efficiency. Molecular dynamics simulations were instrumental in elucidating the dynamic behavior of the tissue-nonspecific alkaline phosphatase isozyme (TNSALP) in the presence of the p.Leu299Pro mutation. The simulations indicated alterations in structural flexibility near the mutation site, with potential ramifications for the enzyme's overall stability and function. These dynamic changes may influence the catalytic efficiency of TNSALP, shedding light on the molecular underpinnings of the observed clinical manifestations within the Tunisian family. The clinical presentation of affected individuals highlighted significant phenotypic heterogeneity, underscoring the complex genotype-phenotype correlations in familial Hypophosphatasia. Variability in age of onset, severity of symptoms, and radiographic features was observed, emphasizing the need for a nuanced understanding of the clinical spectrum associated with the p.Leu299Pro mutation. This study advances our understanding of familial Hypophosphatasia by delineating the molecular consequences of the p.Leu299Pro mutation in the ALPL gene. By integrating genetic, structural, and clinical analyses, we provide insights into disease pathogenesis and lay the groundwork for personalized therapeutic strategies tailored to specific genetic profiles. Our findings underscore the importance of comprehensive genetic and clinical evaluation in guiding precision medicine approaches for familial Hypophosphatasia.

Comparative Analysis of Large Language Models in Emergency Plastic Surgery Decision-Making: The Role of Physical Exam Data.

In the U.S., diagnostic errors are common across various healthcare settings due to factors like complex procedures and multiple healthcare providers, often exacerbated by inadequate initial evaluations. This study explores the role of Large Language Models (LLMs), specifically OpenAI's ChatGPT-4 and Google Gemini, in improving emergency decision-making in plastic and reconstructive surgery by evaluating their effectiveness both with and without physical examination data. Thirty medical vignettes covering emergency conditions such as fractures and nerve injuries were used to assess the diagnostic and management responses of the models. These responses were evaluated by medical professionals against established clinical guidelines, using statistical analyses including the Wilcoxon rank-sum test. Results showed that ChatGPT-4 consistently outperformed Gemini in both diagnosis and management, irrespective of the presence of physical examination data, though no significant differences were noted within each model's performance across different data scenarios. Conclusively, while ChatGPT-4 demonstrates superior accuracy and management capabilities, the addition of physical examination data, though enhancing response detail, did not significantly surpass traditional medical resources. This underscores the utility of AI in supporting clinical decision-making, particularly in scenarios with limited data, suggesting its role as a complement to, rather than a replacement for, comprehensive clinical evaluation and expertise.

Efficacy and Safety of Infliximab Versus Adalimumab in Adult Subjects With Moderate to Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One of the most successful lines for inducing and maintaining clinical remission in subjects with UC is biological therapy with anti-tumor necrosis factor α (anti-TNF) agents, including adalimumab (ADA) and infliximab (IFX).This meta-analysis is an attempt to obtain complementary information driven by real-world experience (RWE) concerning the efficacy and safety of two of the most popular anti-TNFs in treating UC.This is a systematic review and meta-analysis of RWE studies comparing ADA and IFX as naïve anti-TNF agents for the treatment of subjects with UC. Studies were obtained by searching Scopus, Google Scholar, the Cochrane Central Register of Controlled Trials, Embase, and the PubMed Central databases.Patients treated with IFX showed significantly higher induction responses. No statistically significant difference was found in the comparison of response in the maintenance treatment period. Higher overall adverse events were related to IFX treatment, with serious adverse events that were nonsignificantly higher in the ADA-treated group.In conclusion, IFX demonstrated significantly higher induction responses compared to ADA in patients with moderate-to-severe UC. IFX was associated with higher overall adverse events, whereas serious adverse events were non-significantly higher in the ADA-treated group. IFX may be favored as a first-line agent for its induction efficacy, and the choice between IFX and ADA should be individualized based on comprehensive clinical evaluation.

Clinical factors impacting microdissection testicular sperm extraction success in hypogonadal men with nonobstructive azoospermia

To explore factors influencing microdissection testicular sperm extraction (micro-TESE) success in hypogonadal men with nonobstructive azoospermia (NOA). Cohort study. University-affiliated male reproductive health center. 616 consecutive NOA patients with hypogonadism (total testosterone [T] levels <350 ng/dL) undergoing micro-TESE between 2014 and 2021. All patients had no prior sperm retrieval (SR) history. Patients aged 23-55 underwent comprehensive clinical, laboratory, and histopathological diagnostic evaluation for NOA and were further categorized into two cohorts based on pre-SR hormonal stimulation. Multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success, defined as the presence of viable spermatozoa in extracted specimens. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were computed to assess the relationship between SR success and relevant predictors. SR rates were compared between patients receiving or not hormonal stimulation, and logistic regression analysis evaluated the effect of baseline FSH levels (i.e., normogonadotropic vs. hypergonadotropic classes) on SR success. The overall micro-TESE success rate was 56.6%. Baseline FSH levels (aOR 0.97, 95% CI 0.94-0.99, p=0.04), pre-SR hormonal stimulation (aOR 2.54, 1.64-3.93, p=0.0002), presence of clinical varicocele (aOR 0.05, 0.01-0.51, p=0.04), history of previous varicocelectomy (aOR 2.55, 1.26-5.16, p=0.01), and testicular histopathology (p<0.01) were independent predictors of SR success. Among hormone-pretreated patients, pre-micro-TESE T levels and Delta T (absolute increase in T levels from baseline) were associated with SR success (p<0.05). A pre-micro-TESE T level of 418.5 ng/dL (AUC: 0.78) and a Delta T of 258 ng/dL (AUC: 0.76) distinguished patients with positive and negative SR outcomes. Subgroup analysis showed that pre-SR hormonal stimulation yielded a greater benefit for normogonadotropic patients than for those who were hypergonadotropic. This study underscores the association between clinical factors and micro-TESE success in hypogonadal men with NOA. While causality is not established, our findings suggest that these patients may benefit from pre-SR interventions, particularly hormonal stimulation and varicocele repair.

Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.

Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF). Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared to controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles which were then analyzed to predict survival outcomes and investigate associated pathways. Proteomic profiling successfully differentiated IIP from controls. k-means clustering, based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology (GAP) index (C-index 0.794 vs. 0.709). The cluster with the worst prognosis featured decreased inflammatory signaling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B cell-mediated immunity. The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalized treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

Designing Virtual Coaching Solutions

Especially older persons are prone to disabilities and chronic diseases. These chronic conditions pose a worldwide challenge, leading to deteriorating health, economic strain, loss of life, and a decline in the quality of life (QoL). Therefore, healthcare institutions seek to enhance their strategies for disease prevention and management to uphold the well-being of the community. This leads to the need to regain independence and improve QoL to properly rehabilitate the patients. Virtual Coaches (VCs) in the form of Embodied Conversational Agents are seen as a relevant digital intervention to support the continuity of care. The paper at hand reports on a Design Science Research project about implementing a VC solution to support older patients' home rehabilitation. The study underpins four pivotal design principles: Adaptivity, Coaching Strategy, Multi-user Interface, and Sustainable Infrastructure. The final artifact was tested with 80 patients which were supported in continuing their inpatient rehabilitation at home by using a VC. The evaluation shows both positive results for usability and acceptance of the intervention for four different use cases and a positive impact on the QoL. Given the comprehensive clinical evaluation, the system represents a safe and appealing solution for ensuring the continuity of medical rehabilitation care and the access to personalized cognitive and motor function treatments.

Spectrum of Resistance Mechanisms to ALK TKIs in NSCLC: Largest Single-Center Experience from India

Abstract Introduction Anaplastic lymphoma kinase (ALK) rearranged non-small cell lung carcinoma (NSCLC) has emerged as a distinct entity with growing number of potent ALK tyrosine kinase inhibitors (TKIs). Despite showing durable responses and promising survival rates, resistance to these ensue. This is the largest series of repeat biopsies from patients of ALK-positive NSCLC progressing on ALK-directed therapy from this part of the world. Using a combinatorial approach of genomics and histology, we describe the spectrum of various resistance mechanisms encountered. Methods This is a cross-sectional study recruiting ALK-positive NSCLC cases who have progressed on any line ALK TKI and have undergone repeated biopsies followed by genomic sequencing by next-generation sequencing (NGS). Results Thirty-two ALK-positive NSCLC patients progressed on TKI were enrolled. Median age was 53 years (range: 36–75 years) with a male predilection (male:female 1.3:1). Twenty-seven (84.4%) cases harbored an additional resistance mechanism. Eighteen of these harbored an on-target ALK alteration, with L1196M gatekeeper mutation being the most common, in 11 cases, and G1202 alteration in 3 cases. In 9 cases an off-target alteration was detected, the most frequent being TP53 mutation in 8 cases, KRAS mutation in 4 cases and MET amplification in 3 cases. Four patients underwent sequential NGS testing and allele frequency changes in ALK fusion and resistance mechanisms were demonstrated. Sixteen patients have been offered lorlatinib therapy, the median progression-free survival of which has not yet been reached. Conclusion This is the largest series depicting ALK resistance mechanisms from a single center to date. The SPACEWALK study which demonstrated ALK TKI resistance mechanisms using plasma-based genotyping was a multicentric study. The spectrum encountered in this study is distinct from the rest of the world, thus highlighting heterogeneity within ALK-rearranged tumors. Comprehensive clinical evaluation at disease progression coupled with NGS-based genotyping will pave the way for lucid understanding of disease biology, thus aiding in the institution of optimal therapy.

Identification of a pathogenic SMCHD1 variant in a Chinese patient with bosma arhinia microphthalmia syndrome: a case report

BackgroundBosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation.Case presentationIn this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS.ConclusionThis report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.