A Case Series on Acute Mesenteric Ischemia (AMI) Leading to Intestinal Gangrene Following Blunt Trauma to the Abdomen.

The term "acute mesenteric ischemia" (AMI) refers to a set of conditions where the blood supply to various segments of the small intestine is cut off, causing ischemia and subsequent inflammatory changes that might result in bowel gangrene. Estimates place the incidence between 0.09% and 0.2% of all acute surgical hospitalizations. Early diagnosis is essential, despite the entity being a rare cause of abdominal discomfort, because if left untreated, mortality is 50%. Herein, we present a case series of three patients with bowel ischemia following blunt abdominal trauma.

An Unexpected Finding of Isolated Hydatidosis of the Spleen With Concomitant Visceromegaly in an Elderly Female.

Hydatidosis of the spleen is a rare zoonotic clinical entity. The occurrence of isolated splenic hydatid cysts in the absence of these cysts in any other portion of the body is referred to as primary splenic hydatidosis. It is a rare disorder that accounts for only 2% of the burden of hydatid disease worldwide. After the liver and the lungs, the spleen is the organ that is most frequently affected by this condition.

Giant Lipoma of the Arm Masquerading as an Accessory Breast: A Report of a Rare Case.

Accessory breast is an extremely rare condition that develops in 0.4%-6% of females. It is primarily found in the axilla and is frequently misdiagnosed. It is usually bilateral and manifests during pregnancy or lactation as an asymptomatic tumor. The diagnosis of ectopic breast tissue is crucial because it is capable of undergoing the same pathological changes as normal breast tissue, including mastitis, fibrocystic changes of the breast tissue, and, in extreme cases, even malignancy. We present the case of a 40-year-old female who presented with swelling in the left upper arm for the past eight years, which was associated with pain. Initially, accessory breast was kept as the clinical diagnosis. However, further imaging and histological analysis revealed it to be a giant lipoma of the upper arm.

An Incidental Finding of Morgagni Hernia in an Elderly Female and Its Successful Management: A Rare Case Report and Review of Literature.

Morgagni hernia is one of the congenital diaphragmatic hernias, but it can also occur in adults. It usually manifests in childhood, but in rare cases, it may also present in adults. It is linked to a congenital defect during the embryological development of the diaphragm. Uncommon diaphragmatic hernias, also called the foramen of Morgagni hernias, often affect the right side and are found in the anterior mediastinum. Typically asymptomatic in adult patients, the foramen of Morgagni hernia is linked to obesity, trauma, or other causes of elevated intraabdominal pressure. Diagnostic aids include plain pulmonary roentgenograms, contrast-enhanced radiographic investigations of the gastrointestinal tract, computerised tomography, and magnetic resonance imaging tests. We report a rare case of an 85-year-old female with a Morgagni hernia that was incidentally detected on a chest X-ray and was managed successfully.

Contrasting Presentations of Spigelian Hernia in a Single Surgical Unit of a Tertiary Healthcare Center: A Case Series.

A Spigelian hernia is a very rare type of anterior abdominal wall hernia. The etiology revolves around the dehiscence of the transverse abdominis and internal oblique aponeurosis. The majority of Spigelian hernias develop in the lower abdomen where the posterior sheath is absent. This condition is also known as a spontaneous lateral ventral hernia or hernia of the semilunar line. It is mostly asymptomatic and is generally proven by radiological diagnosis. In the worst-case scenario, strangulation of the Spigelian hernia can occur. Here, we report a case series of contrasting presentations of Spigelian hernia in a single surgical unit of a tertiary healthcare center, considering the rarity and associated complications of Spigelian hernia.

Relationship between vascular endothelial growth factor expression and thyroid stimulating hormone level in benign and malignant thyroid lesions.

Background: Vascular endothelial growth factor (VEGF) stimulates angiogenesis, increases vascular permeability and seems to correlate to aggressiveness of tumors. Thyroid cancer has been found to have higher levels of VEGF expression. Thyroid stimulating hormone (TSH) is the most important thyroid hormone, yet few researches have been done on its relationship with VEGF. Aim: To study the clinical and demographic profile of thyroid lesions (benign and malignant) and to explored the relationship between VEGF expression (using immunochemistry) and serum TSH level. Methods: This prospective, observational study includes 61 patients of thyroid lesions who underwent partial, hemi, subtotal or total thyroidectomy as the primary treatment from June 2014 and July 2016. Tissue specimens of thyroid lesions for immunohistochemistry study of VEGF expression were done. Serum TSH was done using Chemiluminiscence technique and correlated to VEGF expression. Results: The mean age of patient was 36.26 ± 11.53 years (range 20-50 years) with female preponderance. Swelling was the most common presenting symptom. Of 61 patients, 37 (60.65%) patients were benign and 24 (39.35%) were malignant thyroid lesions. The mean TSH level in benign group was 1.92 ± 0.94 mIU/liter and malignant group was 2.73 ± 1.74 mIU/liter which was statistically significant (P = 0.023). VEGF expression was strongly positive (3+) in 26 (42.62%) patients and negative/equivocal (1+ & 2+) in 35 (57.38%) patients. In benign group, 10 (27.0%) patients were strongly positive for VEGF whereas in malignant group, 16 (66.7%) patients were strongly positive for VEGF showed significant association (P = 0.002). On comparing TSH level of benign, malignant and total patients separately with VEGF expression, significant association were also observed (P < 0.001, P = 0.004 and P < 0.001, respectively). Conclusion: VEGF was strongly expressed in malignant thyroid lesions which are having high serum concentration of serum TSH level. Serum TSH levels reveal a significant correlation with VEGF expression.

Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer.

Background: The use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. In this study, we have compared the expression of PARP between BC and benign breast disease (BBD) patients and also analyzed the association of PARP expression with clinicopathological parameters in BC. Methods: The study consists of 30 patients with newly diagnosed operable BC who were planned for surgery without neoadjuvant chemotherapy and 15 patients of BBD as a control between 2019 and 2021. Immunohistochemical analyses were performed prospectively on tissue samples. Anti-human PARP1 rabbit polyclonal antibody gives strong nuclear positivity. Internal control was the adipose tissue and the BBD acted as the external control. PARP1 expression was evaluated using the multiplicative quickscore method. Results: The mean age for BC patients was 51.30 ± 10.694 years (range: 25-75 years) while BBD was below 30 years. Overexpression of PARP was present in 25 (83.3%) and weak expression in 5 (16.7%) of BC patients compared to BBD, only 2 (13.3%) patients demonstrated an overexpression of PARP, and 13 (86.6%) patients showed weak expression which showed significant association (P < 0.001). In BC, nuclear PARP (nPARP) overexpression was seen in 22 (73.3%) patients and weak expression of nPARP in 8 (26.7%), whereas 5 (16.7%) patients showed cytoplasmic overexpression. On comparing expression of PARP with clinicopathological parameters, PARP overexpression was significantly associated with older population (age >50 years) (P = 0.002), postmenopausal women (P = 0.029), higher TNM stage (Stage II and III) (P = 0.014), higher histological grade (grade 2) (P = 0.043), and presence of lymphovascular invasion (P = 0.015). Enhanced PARP1 expression is closely correlated with positive estrogen receptor status (P = 0.001) and PR status (P = 0.001). Overall PARP and nPARP overexpression was significantly associated with ER- (P = 0.006 and P = 0.008) and PR-positive (P = 0.006 and P = 0.008) patients. The PARP and nPARP overexpression was significantly associated with nontriple-negative BC patients (P = 0.001 and P = 0.001). Conclusion: We have not come across any study in the literature to compare PARP expression in BC and BBD patients. On the basis of our observations, we concluded that PARP overexpression is a poor prognostic marker in BC.

Effect of negative pressure wound therapy on wound thermometry in diabetic foot ulcers.

Background: Negative pressure wound therapy (NPWT) is the treatment of choice for diabetic foot ulcers (DFUs), and the role of NPWT in the management of DFU is limited. The aim of the study was to compare the effects of NPWT versus conventional dressing (CD) on wound healing in DFU. Materials and Methods: A total of 55 patients were included and divided into two groups: 23 patients were treated with NPWT and 32 patients with CD. The NPWT dressings were changed every 7 days, while the CDs were changed daily. Wound culture sensitivity, wound size, granulation tissue, and pain evaluation (assessed by Visual Analog Scale) were all measured at the start and 3 weeks or until the ulcer was healed. The wound margin temperature was measured at four random sites for thermometric evaluation, and normal limb temperature was also measured for comparison. Patients' satisfaction and treatment costs were also compared. Results: On days 14 and 21, the wound size was reduced significantly in the NPWT group (P < 0.001 and P < 0.001, respectively). The percentage reduction in wound size from baseline to days 7, 14, and 21 was significantly higher in the NPWT group (P = 0.013, P = 0.001, and P = 0.029, respectively). On days 7, 14, and 21, the granulation tissue score was significantly higher in the NPWT group (P = 0.001, P = 0.001, and P < 0.001, respectively). On days 14 and 21, the mean VAS score was significantly low in the NPWT group (P < 0.001 and P < 0.001, respectively). The majority of wounds in the NPWT group were sterile on day 21 compared to those in the CD group (P = 0.008). The majority of patients in the NPWT group had excellent patient satisfaction (P < 0.001). The average material cost was significantly higher in the NPWT group (P = 0.001). The mean wound temperature of the affected limb was significantly higher compared to that of the unaffected limb (P < 0.001). Conclusion: In terms of early formation of granulation tissue, faster wound size reduction, less discomfort, and patient satisfaction, the study indicated that NPWT appeared to be superior. An initial rise in temperature in a DFU may indicate the presence of a pre-ulcerative lesion.

TMT-Based Plasma Proteomics Reveals Dyslipidemia Among Lowlanders During Prolonged Stay at High Altitudes.

Acute exposure to high altitude perturbs physiological parameters and induces an array of molecular changes in healthy lowlanders. However, activation of compensatory mechanisms and biological processes facilitates high altitude acclimatization. A large number of lowlanders stay at high altitude regions from weeks to months for work and professional commitments, and thus are vulnerable to altitude-associated disorders. Despite this, there is a scarcity of information for molecular changes associated with long-term stay at high altitudes. In the present study, we evaluated oxygen saturation (SpO2), heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) of lowlanders after short- (7 days, HA-D7) and long-term (3 months, HA-D150) stay at high altitudes, and used TMT-based proteomics studies to decipher plasma proteome alterations. We observed improvements in SpO2 levels after prolonged stay, while HR, SBP, and DBP remained elevated as compared with short-term stay. Plasma proteomics studies revealed higher levels of apolipoproteins APOB, APOCI, APOCIII, APOE, and APOL, and carbonic anhydrases (CA1 and CA2) during hypoxia exposure. Biological network analysis also identified profound alterations in lipoprotein-associated pathways like plasma lipoprotein assembly, VLDL clearance, chylomicron assembly, chylomicron remodeling, plasma lipoprotein clearance, and chylomicron clearance. In corroboration, lipid profiling revealed higher levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) for HA-D150 whereas high density lipoproteins (HDL) levels were lower as compared with HA-D7 and sea-level indicating dyslipidemia. We also observed higher levels of proinflammatory cytokines IL-6, TNFα, and CRP for HA-D150 along with oxidized LDL (oxLDL), suggesting vascular inflammation and proartherogenic propensity. These results demonstrate that long-term stay at high altitudes exacerbates dyslipidemia and associated disorders.

Effect of neoadjuvant chemotherapy (NAC) on programmed cell death ligand (PD-L1) in patients of carcinoma breast: A prospective study in Indian tertiary care setting.

CONTEXT: Several studies have reported that PD-L1 has shown therapeutic activity in various tumor types. However, its expression changes in a person on administration of NAC which is reported by very few studies. AIMS: To find out the difference in the expression of PD-L1 by tumor cells after the administration of NAC. SETTINGS AND DESIGN: This prospective study was conducted on 30 patients who were diagnosed with locally advanced breast carcinoma (LABC) between 2017 and 2019 and those who received NAC followed by surgery. METHODS AND MATERIAL: Breast cancer specimens were collected using core needle biopsy prior to administration of NAC and IHC was performed. Frequency and staining intensity of PD-L1 by tumor cells were analyzed. PD-L1 expression was dichotomized into two groups according to the frequency distributions of the H-scores. STATISTICAL ANALYSIS USED: The differences in expression of PD-L1 along with various parameters were analyzed using Chi-square test and Student's t test. RESULTS: The mean age of the patients in our study was 51.37 ± 11.37 years. The response of NAC according to the RECIST criteria showed that most of patients (83.3%) showed complete response. Of the 30 cases, 11 (36.7%) patients were PD-L1 positive before the administration of NAC. We found a significant change in expression from positive to negative status, i.e., seven patients changed from positive to negative (p = 0.036). Upon comparing the PD-L1 expression before NAC, significant association was observed between the primary tumor (T) and tumor stage with high PD-L1 expression (p = 0.020 and P = 0.034). After NAC, 18 (69.2%) patients who were ER positive and 18 (69.2%) patients who were PR positive showed negative PD-L1 expression while none of them were positive in PD-L1 positive patients (p = 0.018 and P = 0.018). CONCLUSION: PD-L1 expression in a same person changes upon administration of NAC which may indirectly be used as a predictor of response to NAC.

Cysteine becomes conditionally essential during hypobaric hypoxia and regulates adaptive neuro-physiological responses through CBS/H2S pathway.

Brain is well known for its disproportionate oxygen consumption and high energy-budget for optimal functioning. The decrease in oxygen supply to brain, thus, necessitates rapid activation of adaptive pathways - the absence of which manifest into vivid pathological conditions. Amongst these, oxygen sensing in glio-vascular milieu and H2S-dependent compensatory increase in cerebral blood flow (CBF) is a major adaptive response. We had recently demonstrated that the levels of H2S were significantly decreased during chronic hypobaric hypoxia (HH)-induced neuro-pathological effects. The mechanistic basis of this phenomenon, however, remained to be deciphered. We, here, describe experimental evidence for marked limitation of cysteine during HH - both in animal model as well as human volunteers ascending to high altitude. We show that the preservation of brain cysteine level, employing cysteine pro-drug (N-acetyl-L-cysteine, NAC), markedly curtailed effects of HH - not only on endogenous H2S levels but also, impairment of spatial reference memory in our animal model. We, further, present multiple lines of experimental evidence that the limitation of cysteine was causally governed by physiological propensity of brain to utilize cysteine, in cystathionine beta synthase (CBS)-dependent manner, past its endogenous replenishment potential. Notably, decrease in the levels of brain cysteine manifested despite positive effect (up-regulation) of HH on endogenous cysteine maintenance pathways and thus, qualifying cysteine as a conditionally essential nutrient (CEN) during HH. In brief, our data supports an adaptive, physiological role of CBS-mediated cysteine-utilization pathway - activated to increase endogenous levels of H2S - for optimal responses of brain to hypobaric hypoxia.

Saliva panel of protein candidates: A comprehensive study for assessing high altitude acclimatization.

Altitude acclimatization describes the processes whereby lowland humans respond to decreased partial pressure of oxygen. It refers to the changes seen as beneficial and involves a series of physiological adjustments that compensate for reduced ambient PO2, as opposed to changes that are pathological. Although numerous reports document the physiological effects of exposure to hypobaric hypoxia of varying durations but an interesting aspect overlooked by many researchers is that of acclimatization related studies. As proteome, a dynamic entity responds immediately to external stimuli, protein markers and their trends can be studied to assess acclimatization status of an individual. Compared to blood, the use of saliva is advantageous because sample collection and processing are easy, minimally invasive, low cost and better tolerated by individuals. In this study, we employed iTRAQ based LC-MS/MS technique for comparing saliva samples from humans exposed to hypobaric hypoxia from 7 to 120 days with normoxic controls followed by analysis using Ingenuity Pathway Analysis software and validation by immunoassays. Nearly 67 proteins were found to be differentially expressed in the exposed groups as compared to normoxia indicating modulated canonical pathways as lipid metabolism; acute phase response signalling and proteins as carbonic anhydrase 6, alpha-enolase, albumin, and prolactin inducible protein. Collectively, this study provides the proof of concept for the non-invasive assessment of high altitude acclimatization.

Glucose-6-phosphate dehydrogenase is critical for suppression of cardiac hypertrophy by H2S.

Hydrogen Sulfide (H2S), recently identified as the third endogenously produced gaseous messenger, is a promising therapeutic prospect for multiple cardio-pathological states, including myocardial hypertrophy. The molecular niche of H2S in normal or diseased cardiac cells is, however, sparsely understood. Here, we show that ß-adrenergic receptor (ß-AR) overstimulation, known to produce hypertrophic effects in cardiomyocytes, rapidly decreased endogenous H2S levels. The preservation of intracellular H2S levels under these conditions strongly suppressed hypertrophic responses to adrenergic overstimulation, thus suggesting its intrinsic role in this process. Interestingly, unbiased global transcriptome sequencing analysis revealed an integrated metabolic circuitry, centrally linked by NADPH homeostasis, as the direct target of intracellular H2S augmentation. Within these gene networks, glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme (producing NADPH) in pentose phosphate pathway, emerged as the critical node regulating cellular effects of H2S. Utilizing both cellular and animal model systems, we show that H2S-induced elevated G6PD activity is critical for the suppression of cardiac hypertrophy in response to adrenergic overstimulation. We also describe experimental evidences suggesting multiple processes/pathways involved in regulation of G6PD activity, sustained over extended duration of time, in response to endogenous H2S augmentation. Our data, thus, revealed H2S as a critical endogenous regulator of cardiac metabolic circuitry, and also mechanistic basis for its anti-hypertrophic effects.

Ninety days of repeated gavage administration of Rhodiola imbricata extract in rats.

Rhodiola imbricata is a high-altitude plant, possesses adaptogenic, immunomodulatory, anti-oxidant and cytoprotective activity, and is widely used in traditional medicine. The present study was designed to ascertain the safety of aqueous extract of R. imbricata root when administered by gavage to rats for 90 days. Four groups of animals, each consisting of 15 males and 15 females, were administered 0, 100, 250 or 500 mg kg(-1) extract, in a single dose per day. The experimental rats when administered 100 mg kg(-1) of extract did not show any significant change in their body weight gain, organ/body weight ratio, or histological, hematological and biochemical variables studied. However, at higher doses of 250 and 500 mg kg(-1) extract, an increase in the body weight of rats of both the sexes was apparent without any change in their organ/body weight ratio. Furthermore, a noteworthy increase in plasma glucose and protein levels was recorded at both the higher doses, which were restored to normal after a 2-week withdrawal of treatment. Based on the findings of this study, the no observed effect level was 100 mg kg(-1) body weight per day of aqueous root extract of R. imbricata in rats administered subchronically.

Cooperativity between inhibition of cytosolic K+ efflux and AMPK activation during suppression of hypoxia-induced cellular apoptosis.

Cellular potassium homeostasis has recently emerged as a critical regulator of apoptosis in response to variety of stimuli. However, functional hierarchy of this phenomenon in the apoptotic cascade and therefore, its significance as a pathway for intervention is not fully established. Chronic hypoxia, a known threat to cell survival, also modulates cellular potassium homeostasis. In this study, we tested if hypoxia-induced apoptosis in lymphocytes can be prevented by modulating cellular K+ homeostasis. We observed that chronic hypoxia accelerated the rate of apoptosis in resting murine splenocytes concomitant with cytosolic K+ efflux. We tested several modalities including elevated extracellular potassium besides various K+ channel inhibitors to curtail hypoxia-induced K+ efflux and interestingly, established that the supplementation of KCl in extracellular medium was most effective in preventing hypoxia-induced apoptosis in these cells. Subsequent mechanistic dissection of pathways underlying this phenomenon revealed that besides effectively inhibiting hypoxia-induced efflux of K+ ion and its downstream cell-physiological consequences; elevated extracellular KCl modulated steady state levels of cellular ATP and culminated in stabilization of AMPKα with pro-survival consequences. Also, interestingly, global gene expression profiling revealed that KCl supplementation down regulated a distinct p53-regulated cellular sub-network of genes involved in regulation of DNA replication. Additionally, we present experimental evidence for the functional role of AMPK and p53 activation during suppression of hypoxia-induced apoptosis. In conclusion, our study highlights a novel bimodal effect wherein cooperativity between restoration of K+ homeostasis and a sustainable 'metabolic quiescence' induced by AMPK activation appeared indispensible for curtailing hypoxia-induced apoptosis.

Activity-dependent neuroprotective protein (ADNP)-derived peptide (NAP) ameliorates hypobaric hypoxia induced oxidative stress in rat brain.

Hypobaric hypoxia is a socio-economic problem affecting cognitive, memory and behavior functions. Severe oxidative stress caused by hypobaric hypoxia adversely affects brain areas like cortex, hippocampus, basal ganglia, and cerebellum. In the present study, we have investigated the antioxidant and memory protection efficacy of the synthetic NAP peptide (NAPVSIPQ) during long-term chronic hypobaric hypoxia (7, 14, 21 and 28 days, 25,000ft) in rats. Intranasal supplementation of NAP peptide (2µg/Kg body weight) improved antioxidant status of brain evaluated by biochemical assays for free radical estimation, lipid peroxidation, GSH and GSSG level. Analysis of expression levels of SOD revealed that NAP significantly activated antioxidant genes as compared to hypoxia exposed rats. We have also observed a significant increased expression of Nrf2, the master regulator of antioxidant defense system and its downstream targets such as HO-1, GST and SOD1 by NAP supplementation, suggesting activation of Nrf2-mediated antioxidant defense response. In corroboration, our results also demonstrate that NAP supplementation improved the memory function assessed with radial arm maze. These cumulative results suggest the therapeutic potential of NAP peptide for ameliorating hypobaric hypoxia-induced oxidative stress.