This document discusses the expression of CD44 in minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) and its association with clinical and histopathological prognostic factors. It finds that CD44 positivity correlates with lower estimated GFR and higher serum creatinine, both poor prognostic signs. It also associates CD44 positivity with segmental sclerosis and tubular atrophy/interstitial fibrosis. While CD44 positivity makes it a sensitive marker for FSGS, it is also detected in some cases of MCNS, suggesting a continuum between the two.
Clinically inapparent adrenal masses which are incidentally detected have become a common problem in everyday practice. Approximately 5-20% of adrenal incidentalomas present subclini- cal cortisol hypersecretion which is characterized by subtle alterations of the hypothalamic- pituitary-adrenal axis due to adrenal autonomy. this disorder has been described as subclinical cushing’s syndrome, since there is no typical clinical phenotype. the diagnosis of subclinical cushing’s syndrome is based on biochemical evaluation; however, there is still no consensus for the biochemical diagnostic criteria. An abnormal 1mg dexamethasone suppression test (Dst) as initial screening test in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis has been advocated by most experts for the diagnosis of subclinical cushing’s syndrome. Dst is the main method of establishing the diagnosis, while there is inhomogeneity of the information that other tests provide. Arterial hypertension, diabetes mellitus type 2 or impaired glucose tolerance, central obesity, osteoporosis/vertebral fractures and dyslipidemia are considered as detrimental effects of chronic subtle cortisol excess, although there is no proven causal relationship between subclinical cortisol hyperse- cretion and these morbidities. therapeutic strategies include careful observation along with medical treatment of morbidities potentially related to subtle cortisol hypersecretion versus laparoscopic adrenalectomy. the optimal management of patients with subclinical cushing’s syndrome is not yet defined. the conservative approach is appropriate for the majority of these patients; however, the duration of follow-up and the frequency of periodical evaluation still remain open issues. surgical resection may be beneficial for patients with hypertension, diabetes mellitus type 2 or abnormal glucose tolerance and obesity.
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy. Several studies reported a sex disparity
in ASCC prognosis showing a better survival for female compared
to men. Methods: we examined 1,380 patients with ASCC who received comprehensive genomic profiling as part of routine clinical
care and present key
Poster at EMBL: Diagnosis and monitoring of Leptomeningeal Disease using Circ...Ronak Shah
Leptomeningeal metastases (LM) in solid tumors (ST) represent a devastating complication of cancer with a median survival of only 12-14 weeks after diagnosis; however, establishing the diagnosis of LM can be difficult, particularly at early stages before the patient is disabled. The diagnosis is based on CSF cytologic analysis and/or MRI findings. Brain and spine MRIs have been increasingly preferred for the initial evaluation of LM because of their non-invasive nature and convenience to patients. However, MRI findings are negative in 25%-50% of patients, and unequivocal findings may only appear in late-stage disease when the patient is already debilitated. CSF cytologic analysis provides diagnostic confirmation of LM but is associated with a relatively low sensitivity (approximately 50% on the first lumbar puncture) and is highly examiner-dependent. Improved diagnostic tools are required to facilitate early diagnosis. To this end, we explored whether sufficient quantity and quality of DNA can be isolated from CSF for genomic study and whether the CSF pellet or CSF supernatant, would be more suitable for detecting cfDNA. We used an in-house sequencing assay, MSK-IMPACT, to interrogate 341 clinically relevant cancer genes in tumor-derived cfDNA from 53 patients. Results of CSF cfDNA were compared to standard CSF cytopathologic analysis from that same CSF sample and with MRI findings performed at the same time. When possible, we compared CSF cfDNA with DNA from tumor tissue (primary tumor and non-CNS sites) to determine similarities and differences in genetic alterations between these different compartments.
Clinically inapparent adrenal masses which are incidentally detected have become a common problem in everyday practice. Approximately 5-20% of adrenal incidentalomas present subclini- cal cortisol hypersecretion which is characterized by subtle alterations of the hypothalamic- pituitary-adrenal axis due to adrenal autonomy. this disorder has been described as subclinical cushing’s syndrome, since there is no typical clinical phenotype. the diagnosis of subclinical cushing’s syndrome is based on biochemical evaluation; however, there is still no consensus for the biochemical diagnostic criteria. An abnormal 1mg dexamethasone suppression test (Dst) as initial screening test in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis has been advocated by most experts for the diagnosis of subclinical cushing’s syndrome. Dst is the main method of establishing the diagnosis, while there is inhomogeneity of the information that other tests provide. Arterial hypertension, diabetes mellitus type 2 or impaired glucose tolerance, central obesity, osteoporosis/vertebral fractures and dyslipidemia are considered as detrimental effects of chronic subtle cortisol excess, although there is no proven causal relationship between subclinical cortisol hyperse- cretion and these morbidities. therapeutic strategies include careful observation along with medical treatment of morbidities potentially related to subtle cortisol hypersecretion versus laparoscopic adrenalectomy. the optimal management of patients with subclinical cushing’s syndrome is not yet defined. the conservative approach is appropriate for the majority of these patients; however, the duration of follow-up and the frequency of periodical evaluation still remain open issues. surgical resection may be beneficial for patients with hypertension, diabetes mellitus type 2 or abnormal glucose tolerance and obesity.
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy. Several studies reported a sex disparity
in ASCC prognosis showing a better survival for female compared
to men. Methods: we examined 1,380 patients with ASCC who received comprehensive genomic profiling as part of routine clinical
care and present key
Poster at EMBL: Diagnosis and monitoring of Leptomeningeal Disease using Circ...Ronak Shah
Leptomeningeal metastases (LM) in solid tumors (ST) represent a devastating complication of cancer with a median survival of only 12-14 weeks after diagnosis; however, establishing the diagnosis of LM can be difficult, particularly at early stages before the patient is disabled. The diagnosis is based on CSF cytologic analysis and/or MRI findings. Brain and spine MRIs have been increasingly preferred for the initial evaluation of LM because of their non-invasive nature and convenience to patients. However, MRI findings are negative in 25%-50% of patients, and unequivocal findings may only appear in late-stage disease when the patient is already debilitated. CSF cytologic analysis provides diagnostic confirmation of LM but is associated with a relatively low sensitivity (approximately 50% on the first lumbar puncture) and is highly examiner-dependent. Improved diagnostic tools are required to facilitate early diagnosis. To this end, we explored whether sufficient quantity and quality of DNA can be isolated from CSF for genomic study and whether the CSF pellet or CSF supernatant, would be more suitable for detecting cfDNA. We used an in-house sequencing assay, MSK-IMPACT, to interrogate 341 clinically relevant cancer genes in tumor-derived cfDNA from 53 patients. Results of CSF cfDNA were compared to standard CSF cytopathologic analysis from that same CSF sample and with MRI findings performed at the same time. When possible, we compared CSF cfDNA with DNA from tumor tissue (primary tumor and non-CNS sites) to determine similarities and differences in genetic alterations between these different compartments.
Clinical diagnosis of chronic myeloid leukemia by real time polymerase chain ...Teboho Mooko
Oncology study i did in my third year (2014). the study was basically about monitoring Chronic Myeloid leukemia (CML) using Real-Time PCR techniques to check how patients from Universitas Hospital responded to the treatment of Gleevec drug.
Clinical diagnosis of chronic myeloid leukemia by real time polymerase chain ...Teboho Mooko
Oncology study i did in my third year (2014). the study was basically about monitoring Chronic Myeloid leukemia (CML) using Real-Time PCR techniques to check how patients from Universitas Hospital responded to the treatment of Gleevec drug.
Similar to CD44_marker_introduction_immunohistochemistry.pptx (16)
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
1. AIMS
To assess the expression of CD44 in MCNS and FSGS and to evaluate its
association with the known clinical and histopathological prognostic
factors.
2. A statistical significance was noted between serum creatinine and CD44 positivity in the
current study.
Hunt et al. proposed that an elevated plasma creatinine, either at onset or at 1 year and
heavy urinary protein loss persisting at 1 year were the factors most significantly related
to eventual ESRD, thus indicating the prognostic significance.
Korbet et al. could demonstrate that increased baseline creatinine value of >1.3 mg/dl
as a poor prognostic factor, and also 30% of patients with renal insufficiency (serum
creatinine ≥3.5 mg/dl) ended up with ESRD.
3. Estimated GFR (eGFR)
GFR represents the flow of plasma into the Bowman's space over a specified period. It
is a chief measure of kidney function.
A decrease in GFR is considered a poor prognostic factor in NS.
There was a statistical association between eGFR and CD44 positivity in the present
study which correlated with other studies.
These studies demonstrated that CD44 positive cases had lower baseline eGFR, and
on follow up had a significant fall in eGFR.
Martinelli et al. could not demonstrate any prognostic significance for eGFR. However,
a reduced baseline GFR, indeed predicts the progression of the disease..
4. Histopathology
Mesangial hypercellularity
Mesangial changes following a glomerular injury include the production of
chemoattractants for inflammatory cells, proliferation of mesangial cells, and increased
ECM production.
Mesangial expansion with or without hypercellularity can cause compression of
glomerular capillaries causing decreased GFR which results in disease progression
The lack of association between mesangial hypercellularity and CD44 positivity as in
other studies could be due to a smaller sample size.
5. Podocyte hypercellularity
Six of the 30 FSGS patients (20.0%) had podocyte hypercellularity.
There was no statistical association between CD44 positivity and podocyte hypercellularity.
This is not at all surprising because glomerulomegaly in FSGS following a podocyte injury causes an
increase in GBM surface area.
In order to maintain coverage, podocyte tries to hypertrophy initially but gets arrested in the G1 phase
of the cell cycle leading to actin rearrangement, detachment, and finally cell death.
Podocytes may die by apoptosis, necrosis, necroptosis, and death due to decreased autophagy.
Podocyte depletion is well documented in both experimental animals and human kidneys.
Thus the six cases with podocyte hypercellularity in the current study may be due to the reparative
mechanisms in play.
6. Segmental sclerosis
Segmental sclerosis can occur due to post compensatory hemodynamic changes
following nephron loss or by primary podocyte damage due to mediators released from
mesangial cells following a glomerular injury.
The association between segmental sclerosis and CD44 positivity was in line with the
findings by Paik et al.
The more advanced the injury to the podocytes, the more decline in the renal function
and progression to ESRD ensues.
7. Tubular atrophy/interstitial fibrosis
Regardless of the etiology, TA is defined as the disappearance of either individual tubular
epithelial cells or entire tubules, often in conjunction with interstitial fibrosis.
TA is found to be a better predictor of the progression of renal failureThe association
between segmental sclerosis and CD44 positivity was in line with the findings by Paik et al.
Fibrosis on renal biopsy is an index of functional renal impairment and a predictor of
disease progression.
Studies have shown that IF > 50% are poor candidates for therapy effectiveness.
There was a statistical association between TA/IF with CD44 positivity (p = 0.027). This was
correlating with other studies.
Studies have shown that TA/IF > 20/30% is associated with a poor prognosis.
However, some studies failed to demonstrate any prognostic significance.
TA/IF due to any disease process carries a worse prognosis.
8. Histological diagnosis
Several possible explanations are given for the decreased yield in histological diagnosis of
FSGS:
(1) if glomerular scars are uniformly distributed in a biopsy with 10–30 glomeruli, the diagnostic
accuracy for the detection of at least one scarred glomerulus will be 80% when at least 10% of
juxtamedullary glomeruli or 20% of other cortical glomeruli are scarred.
(2) With an average of 20 glomeruli with 20%–60% glomerular sclerosis, the predicte error rate is ±
50% for the extent of glomerular involvement.
Thus the distinction of MCD versus early FSGS may be difficult, particularly when biopsies
are small and diagnostic segmental lesions are not adequately sampled or when the
glomerular injury is in an early pre-sclerotic stage.
This is where activated PECs come into the picture. Activated PECs show de novo
expression of CD44 and thus help pick up early FSGS lesions surpassing the limitations
mentioned above
A statistical association was established between CD44 positivity and histological diagnosis.
This was corroborated by Hunt et al.
However, Martinelli et al. could not establish any prognostic significance with morphological
diagnosis.
9. Immunohistochemistry
The 90% CD44 positivity in FSGS biopsies makes it a sensitive marker. But we did
encounter CD44 negative FSGS cases.
This has decreased the specificity of the marker to 76.67%.
This could be explained by the fact that the sclerotic lesions could have been lost on
serial sectioning of the biopsies used for immuno-histological assessment.
Regarding the absence of sclerotic lesions in CD44 positive histologically diagnosed
MCNS cases, several explanations are possible.
Studies have shown that the small sclerotic lesions in CD44 positive MCNS cases were
not detectable in consecutive PAS-stained sections, prepared after the immunohistologic
analysis.
10. Thus, the cells expressing CD44 on the glomerular tuft could be an earlier marker than overt
sclerosis; whether these patients follow a course indicative of FSGS could not be evaluated
in those studies due to the lack of follow up.
In the present study, the original diagnosis was made on the sections of the same biopsy
analyzed for immunohistochemistry.
Although we examined only those biopsies with eight or more glomeruli, the sclerotic lesions
could still be present in other glomeruli or in different planes of sectioning.
We could not demonstrate any sclerotic lesions in these CD44 positive MCNS cases even
after reviewing the slides.
Surprisingly, the original diagnosis is normally based on 32 serial sections of a single
biopsy, thereby examining several planes of sectioning.
We stained and analyzed only one biopsy section per PEC marker staining, and still, it could
pick up these CD 44 positive cells which were missed in the earlier 32 sections.
This highlights the sensitivity of CD44. Immunohistologic staining for PEC markers could
detect sclerotic lesions in 25% of the biopsies originally diagnosed as MCNS in a recent
study,[1] which was reflected in the present study too.
11. The differentiation of MCNS from primary FSGS relies exclusively on the histologic
findings in the biopsy, emphasizing the relevance of the pathologic analysis.
In general, the lesions detected by PEC markers were small and often located close to
the glomerular tip.
The focal and segmental nature of FSGS, especially for these small lesions, may
explain why the lesions were missed in the original sections.
In fact, it is a well-known fact that small lesions particularly at the glomerular tip may be
missed in biopsies initially diagnosed as MCNS.
Another explanation is that CD44 could stain migrated PECs even before overt
sclerosis develops, reiterating that diagnosis made by light microscopy alone may be
insufficient.
12. The positivity of CD44 favors the view that MCNS and FSGS are a continuum of the
same entity and that in steroid responsive MCNS too prognosis can be uncertain
because of morphological transition to FSGS on repeat biopsy and subsequent renal
impairment develops later.
A hypothesis that a greater number of glomeruli present in the renal biopsies could be a
reason why CD44 positivity could be demonstrated in those histologically diagnosed
MCNS cases, has been disproved by several studies.
Present study also failed to demonstrate any statistical significance between these
variables (p = 0.131).
In fact, CD44 positivity in MCNS was seen more in biopsies with less than 25 glomeruli
in them.
13. Next, we compared the proven poor prognostic factors with CD44 positivity in the
MCNS group to speculate possible poor prognosis and thus indirectly to a diagnosis of
FSGS.
The mean serum creatinine among the CD44 positive MCNS cases was 1.466 ± 0.641
mg/dl, which is not significantly high.
Even other parameters both clinical and laboratory parameters could not give a hint
towards FSGS.
Five biopsies did not show any TA or IF. Even the remaining two cases also had TA/IF <
15%.
However, the glomeruli in the vicinity of TA/IF were histologically unremarkable.
There was no podocyte hypercellularity in any of these cases, again ruling out another
histological clue that could have made the pathologist think of an alternative diagnosis.
This further underscores the fact that CD44 can prove to be a game-changer to detect
activated PECs when light microscopy does not show any sclerotic lesion.