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Background: Morbidity and mortality envisaged by chronic kidney disease (CKD) remains a health menace throughout the world. Complications, incidence, prevalence, the impact of dietary recommendations, risk factors, outcome, and management strategies have not been rationalized due to several adversities resulting in escalated death rates. The objective of this study was to evaluate and establish a malnutrition information score (MIS) as a means of ease of CKD prevention and progression. MIS underlies the consistencies in findings through MIS show higher values can be corroborated to recommend the augmentation parameters in utilizing MICS techniques and other healthcare types of equipments. Methods: A randomized, non-biased sampling of patients presenting to dialysis unit with their maintenance schedule program in the nephrology department of Medical Unit-3 of PIMS, Islamabad were introspected for inclusions. Personal history, BSF thickness and MAC values were measured, and MAMC was calculated by = MAC – (3.1416 x TSF). The study was conducted in the Department of Nephrology, PIMS, Islamabad for a duration of six months. Results: The study conducted across 59 male patients and 33female patients indicate that males are more susceptible to CKD than females as evidenced by clinical stability of 67%. Appetite loss, degree of severity, Co-morbidity, BMI, MIS range, and clinical stability status of 100 study participants show variable indices indicating the stress on personal and family history of the patients. MIS pose as an indicator for determining the apt Malnutrition-Inflammation Complex Syndrome (MICS) and other types of equipments for treating CKD. Conclusion: CKD patients undergoing maintenance hemodialysis analyzed for dietary balance affirm the utility of MIS in determining the MICS and other types of healthcare equipments indirectly in ensuring reduction in morbidity and mortality.

Aim: To ascertain efficacy of Valsartan, an angiotensin receptor blocker (ARB) in reducing microalbuminuria in obese verses non obese patients. Methods: This comparative study was done in Department of Nephrology Pakistan Institute of Medical Sciences Islamabad from July 1, 2018 to December 31, 1018. Patients fulfilling selection criteria were enrolled and categorized as two groups obese & non-obese; both groups were given valsartan. Urine ACR and serum creatinine was followed every month for 6 months. Results: Average age of all cases as 52.06 ± 4.11 years while the mean age in obese and non-obese cases was 52.48 ± 4.25 years and 51.63 ± 3.95 years, respectively. The mean change in Urine ACR (from baseline to 6th months) in obese cases was 41.76 ± 25.81 and non-obese cases was 76.05 ± 7.63, p-value 0.05 while at 3rd, 4th month was statistically lower as compare to baseline urine ACR, p-value < 0.05. Moreover, in non-obese cases the mean urine ACR was statistically decreased at 1st, 2nd, 3rd, 4th, 5th and 6th month when compared with baseline, p-value < 0.001. At 4th month in obese cases none of the cases achieved ACR < 30 while in non-obese cases 4(7.4%) cases achieved ACR < 30 with significantly higher frequency in non-obese cases, p-value < 0.05. At 4th month in obese cases 12(22.2%) cases achieved ACR < 30 while in non-obese cases 31(57.4%) cases achieved ACR < 30 with significantly higher frequency in non-obese cases, p-value < 0.001. At 6th month in obese cases 20(37%) cases achieved ACR < 30 while in non-obese cases 41(75.9%) cases achieved ACR < 30 with significantly higher frequency in non-obese cases, p-value < 0.001. Conclusion: Valsartan is more effective in reducing microalbuminuria in non-obese patients as compared to obese patients. Keywords: Diabetes mellitus, obesity, microalbuminuria, Valsartan

Objectives: To determine and compare vitamin D status in chronic hepatitis C patients and normal healthy matching controls. Study Design: A case control study. Setting: A private clinic of Peshawar. Period: 1st November 2015 to 31st January 2016. Material & Methods: Fifty clinically normal young adults and fifty non cirrhotic chronic hepatitis C patients were included in the study. Vitamin D was determined by electro chemiluminescence. Student t test was used to analyze the data in SPSS version 21. Results: The mean age of the study population was 30.68+ 5. Vitamin D deficiency was divided into three categories. 21% of the study population had severe vitamin D deficiency, 33% had mild to moderate deficiency and 46% of the study population had normal levels. Females population were more vitamin D deficient as compared to males (p-value

Juvenile polyposis syndrome is a rare inherited disorder that afflicts the gastrointestinal system. It usually occurs as a result of gene mutations; to date, several gene mutations, including those involving the bone morphogenetic protein receptor type IA (BMPR1A) gene, have been implicated in heralding the onset of the ailment. The disease is characterized by the infiltration of the gastrointestinal system with numerous hamartomas, which are predominantly benign. However, if left untreated, the hamartomas can undergo malignant transformations. Timely diagnosis and prompt surgical intervention are, therefore, imperative in portending favorable disease outcomes. We hereby delineate the case of a patient who presented with rectal prolapse and bleeding per rectum. Further diagnostic workup revealed the presence of polyps throughout the colon and the rectum, thereby insinuating a diagnosis of non-familial juvenile polyposis syndrome. The patient was managed through open surgery and continues to do well with no indications of disease recurrence.

Parotid glands, which are predominantly composed of serous acini, are the largest salivary glands in the human body. Mucoepidermoid carcinoma (MEC) of the parotid gland is the most common parotid tumour that routinely presents as a painless, fixed mass below the ears. However, its presentation as a fungating mass remains exceedingly rare. Due to the intimate anatomical relationship between the parotid gland and the facial nerve, parotid malignancies can culminate in facial nerve palsy, posing an onerous surgical challenge. In this paper, we chronicle the case of a male who presented with a fungating/exophytic mass and facial nerve weakness. A superficial parotidectomy was performed, and the eventual histopathological workup divulged an advanced mucoepidermoid parotid carcinoma entirely encasing the marginal mandibular nerve. Consequently, the marginal mandibular nerve was sacrificed, alluding to the remarkable surgical challenge encountered. Clinically, this manifested as an impairment of the motor function in the patient's left lower lip.

Hydatidosis is an infective ailment that is caused by the parasite echinococcus granulosus. The parasitic infection typically produces cysts filled with excessive quantity of fluid and most commonly afflicts the liver. While secondary hydatidosis remains exceedingly rare, cases of hydatidosis in organs such as the ovaries and the fallopian tubes have been documented in the literature. In such instances, the patients present with a vague constellation of symptoms, including abdominal distension and vague abdominal pain. Herein, we elucidate the case of a female patient who presented with massive abdominal swelling on a background history significant for hydatid liver disease. Intraoperative findings included a left adnexal mass, which was eventually established to be an ovarian adenocarcinoma coexisting with secondary ovarian hydatidosis.

Background Affections of the gallbladder remain exceedingly ubiquitous and often warrant surgical intervention. The histopathological patterns represent a spectrum, ranging from cholecystitis to gallbladder carcinoma. The present study aims to delineate the occurrence of various gallbladder histopathologies in a tertiary care hospital in Pakistan. Methods A retrospective study was conducted at Maroof International Hospital, Islamabad, Pakistan. Histopathological records of 442 gallbladder specimens obtained from cholecystectomy were analysed. The prevalence of various histopathological outcomes was assessed. The data were eventually analysed using the SPSS 23.0 software (Armonk, NY: IBM Corp.). Thereafter, the distribution of various gallbladder histopathologies was tabulated across gender. Results Of the 442 patients included, 330 were females and 112 were males, with the mean age hovering at 45.77±14.65 years. The most common histopathological findings were chronic cholecystitis and cholesterolosis, observed in 78.6% and 32.8% of the patients, respectively. While only one case of gallbladder adenocarcinoma was observed, multiple specimens divulged premalignant lesions including reactive atypia and intestinal metaplasia. Conclusions Diseases of the gallbladder often mandate prompt surgical intervention. Of these, chronic cholecystitis, which is an established risk factor for gallbladder carcinoma, is exceedingly common. The employment of histopathological techniques remains imperative in the detection of premalignant and malignant lesions that might otherwise evade macroscopic detection and thus progress to adenocarcinoma.

Aortic valve stenosis (AVS) is a prevailing and life-threatening cardiovascular disease in adults over 75 years of age. However, the molecular mechanisms governing the pathogenesis of AVS are yet to be fully unraveled. With accumulating evidence that Wnt signaling plays a key role in the development of AVS, the involvement of Wnt molecules has become an integral study target in AVS pathogenesis. Thus, we hypothesized that the Wnt/β-catenin pathway mediators, SFRP2, DVL2, GSK3β and β-catenin are dysregulated in patients with AVS. Using immunohistochemistry, Real-Time qPCR and Western blotting, we investigated the presence of SFRP2, GSK-3β, DVL2, and β-catenin in normal and stenotic human aortic valves. Markedly higher mRNA and protein expression of GSK-3β, DVL2, β-catenin and SFRP2 were found in stenotic aortic valves. This was further corroborated by observation of their abundant immunostaining, which displayed strong immunoreactivity in diseased aortic valves. Proteomic analyses of selective GSK3b inhibition in calcifying human aortic valve interstitial cells (HAVICs) revealed enrichment of proteins involved organophosphate metabolism, while reducing the activation of pathogenic biomolecular processes. Lastly, use of the potent calcification inhibitor, Fetuin A, in calcifying HAVICs significantly reduced the expression of Wnt signaling genes Wnt3a, Wnt5a, Wnt5b, and Wnt11. The current findings of altered expression of canonical Wnt signaling in AVS suggest a possible role for regulatory Wnts in AVS. Hence, future studies focused on targeting these molecules are warranted to underline their role in the pathogenesis of the disease.

Breast sarcomas remain a rare malignancy and are noted to portend a particularly dismal prognosis. Due to their high rates of recurrence, a surgical excision with negative margins remains the preferred treatment modality. Nevertheless, their sparse prevalence often poses a diagnostic conundrum. In this report, we chronicle the case of a 46-year-old female with a recurrent breast sarcoma that was treated with wide local excision. Interestingly, no flap reconstruction, skin graft surgery, or primary wound closure was performed, and the resultant wound was left to heal by secondary intention. The patient continues to do well to date, with no postoperative complications.

Background Breast cancer remains the most common cause of cancer related mortality amongst women in Pakistan. Postoperative complications can demoralize the patients and potentially delay adjuvant treatment, leading to adverse outcomes. The overarching aim of the study is to delineate the early postoperative outcomes of breast cancer surgery in Pakistan. Materials and Methods A retrospective study involving patients who underwent breast cancer surgery from June 2016 to December 2019 was conducted. Perioperative morbidities (30 days) were evaluated and documented. The results obtained were analyzed using the SPSS 23 software (IBM Corporation, Armonk, NY). Results A total of 94 patients were included in the study, with the mean age of 50±12.8 years. Breast conserving surgery was performed in 32% (n=31) of the patients, while the remaining 68% (n=63) underwent modified radical mastectomy. The most common complications were seroma formation, flap necrosis and hematoma formation and were observed in 5.3% (n=5), 4.3% (n=4) and 3.2% (n=3) of the patients, respectively. Conclusion Early postoperative complications can delay the commencement of adjuvant systemic therapy required for further management of breast cancer. These complications elicit equally grave consequences for patients undergoing breast conserving surgery and modified radical mastectomy.

Introduction Soft tissue sarcomas remain an exceedingly rare malignancy. While soft tissue sarcomas boast a high mortality rate, their characteristics and behavior patterns are poorly understood. This study aims to evaluate the various aspects that pertain to soft tissue sarcomas, including their histology, tumor characteristics, survival rates, and therapeutic modalities. Methods A retrospective study analyzing the data from 19 patients presenting over four years with a histologically confirmed diagnosis of soft tissue sarcomas was conducted. The patients were studied for various parameters, including tumor site and the particular pathological subtypes. The data obtained were analyzed using the SPSS 23.0 statistical software (IBM Corporation, Armonk, NY), and the results were then tabulated. Results A total of 19 patients with a confirmed diagnosis of a soft tissue sarcoma were included in the study. The mean age of the patients included was 45.32 ± 16.88 years. Wide local excision was the most common surgical procedure employed for the resection of these tumors. Within the cohort, the mortality rate was noted to hover at 10.52%. Gastrointestinal stromal tumors were observed in 21% of the patients and were therefore the most common histological subtype. Of the patients included, 42.10% required blood transfusion during the perioperative time. Most of the tumors were noted to be intermediate grade, with high-grade tumors observed in 26.3% of the cases. Conclusion Soft tissue sarcomas remain a rare but potent cause of death in developing countries. The diversity of the tissues that they afflict renders their prompt detection a diagnostic challenge. A meticulous exploration of the various characteristics honed by soft tissue sarcomas, such as the particular histological subtype and the associated mortality rates, can better elucidate the prognosis and the eventual disease outcomes.

The urachal sinus is a vestigial remnant that ensues in the aftermath of incomplete obliteration of the embryonic urachus. Urachal sinuses often remain asymptomatic, being discovered incidentally in instances where they are complicated with a superimposed infection or abscess. Due to their rare occurrence in adults, urachal sinuses are rarely included in the list of differential diagnosis surrounding umbilical pain in adult patients. We hereby delineate a unique case of a urachal sinus in a 26-year-old male patient. Due to the presence of an abscess in a hirsute male, a presumptive diagnosis of an umbilical pilonidal sinus was suspected. However, further diagnostic workup divulged an unequivocal diagnosis of a urachal sinus complicated by an abscess formation.

Ovarian tumors occurring secondarily to metastatic colorectal carcinoma remain a rare occurrence. Since ovarian tumors remain predominantly asymptomatic in the initial stages, they are often diagnosed incidentally. The vague, non-specific symptoms elicited by a secondary ovarian carcinoma, coupled with a histopathology remarkably similar to that evoked by primary ovarian tumors, render its ascertainment a diagnostic challenge. We hereby delineate an interesting case of a metachronous ovarian adenocarcinoma in a 19-year-old patient with a prior medical history significant for colorectal carcinoma treated with hemicolectomy. Subsequent diagnostic workup divulged a mass in her left adnexal region, which was ultimately diagnosed as a metastatic colon adenocarcinoma to the ovary. Unfortunately, the patient succumbed to the aggressive malignancy and did not survive. We therefore aim to accentuate the diagnostic and therapeutic dilemmas fomented by ovarian adenocarcinomas that arise secondarily to primary colorectal cancers.

Ovarian carcinomas remain a cause of soaring mortality in the general population. Due to their anatomical location in the pelvis, malignant ovarian transformations often evade early detection, reaching astronomical proportions before eliciting clinically obvious symptoms. Epithelial ovarian carcinomas encompass a concoction of tumours derived from the ovarian surface epithelium, and are further subdivided into several subtypes ascertained primarily through histopathological workup. Of these subtypes, endometrioid ovarian carcinoma is noted to be a particularly well-differentiated tumour that often presents early in the disease course. Contrarily, advanced-stage tumours manifest a vague constellation of symptoms, such as abdominal distension and bloating, resulting in dilatory tumour detection. We hereby delineate an interesting case of a high-grade ovarian endometrioid carcinoma that, due to its vague presenting symptoms and a concomitant history of amenorrhea, was erroneously regarded as pregnancy. Subsequent diagnostic workup divulged a bilateral endometrioid ovarian carcinoma with associated serosal involvement and extensive lymph-vascular invasion.

Liposarcomas are exceedingly rare entities that evoke malignant transformation of connective tissue and fat cells. These tumours occur throughout the soft tissues of the body, afflicting a myriad of regions. In the adult population, liposarcomas represent the most prevalent subtype of sarcomas, and often arise de novo. Retroperitoneal liposarcomas (RLS) are a ubiquitous subset of sarcomas that, due to their deep location in the hollow abdomen, can grow to astronomical proportions before manifesting any noticeable symptoms; a prompt diagnosis of RLS is therefore often rendered dilatory. We hereby delineate the case of a 43-year-old woman who presented with vague left hemiabdominal distention and discomfort. A subsequent computed tomography scan divulged a giant retroperitoneal growth impaling on and thus displacing the pancreas. A compartmental, en bloc resection was performed, with subsequent histopathology of the excised specimen revealing a well-differentiated liposarcoma. The surgical intervention was curative and led to an uneventful recovery. This paper highlights the pertinence of surgical management as an appropriate treatment modality for a complete resection of RLS.

Osteoporotic patients being treated with bisphosphonates present an interesting dilemma when removing hardware such as dynamic hip screws “DHS”. In this paper, we describe the case of a 66-year-old osteoporotic patient who was placed on long term bisphosphonate therapy after sustaining an intertrochanteric hip fracture which was stabilized with a DHS. She presented with a subtrochantric fracture on the ipsilateral side. She was planned for DHS removal and intramedullary nailing. Removal of the dynamic hip screw proved to be difficult, likely due to possible cold welding of the DHS to the barrel of the side plate and sclerotic bone formation around the hardware secondary to the extended bisphosphonate use. The patient had an intra-operative femoral neck fracture while attempting the DHS removal. We had to convert to an unanticipated total hip replacement. Careful considerations should be taken when removing hardware from patients on long term bisphosphonate treatment. Keywords: Case report, Orthopedic surgery, Bisphosphonate, Subtrochanteric fracture

Aortic valve stenosis (AVS) affects a significant percentage of our elderly population and younger subjects with familial hypercholesterolemia. Lipoprotein(a) [Lp(a)] has been associated with AVS in recent genetic studies. The purpose of this study was to determine the effects of Lp(a) on human aortic valve interstitial cells (HAVICs), and to identify apolipoproteins and phospholipids in diseased human aortic valves.We examined the effects of Lp(a) on HAVICs mineralization and oxidant formation. Proteomic analyses were used to determine the effects of Lp(a) on downstream intracellular markers. We also used mass spectroscopy to identify the different lipoproteins and oxidized phospholipids in calcified aortic valves.HAVICs incubated with either LDL or Lp(a) had significantly higher calcium deposition, compared to control (p0.001), with Lp(a) having the most significant effect (p0.01) compared to LDL. Proteomic analysis after 10 days of treatment with Lp(a) resulted in enrichment of proteins involved in calcium deposition and vesicle biogenesis. Treatment of HAVICs with Lp(a) significantly increased ROS formation (p0.05). Patients with calcific aortic stenosis had higher plasma Lp(a) concentrations compared to non-CAD individuals (p0.001). LC-MS/MS revealed the presence of apolipoproteins and phospholipids in calcified human aortic valves.The present study outlines an association between Lp(a) and AVS, and suggests that Lp(a) may serve as a potential target for therapeutic purposes to manage the progression of AVS.

Introduction: Autoimmune Hepatitis (AIH) is a rare liver injury known to cause approximately 13% of acute liver failure cases in the United States. Drug-induced AIH has similar clinical, serological and histological features of AIH but is less likely to require long term immunosuppression or to relapse after discontinuation of immunosuppressants. It is mostly associated with nitrofurantoin, minocycline, hydralazine, and methyldopa, however other medications may be culprits. Herein, we present a patient with drug-induced AIH with possible relation to Pfizer-BioNTech COVID-19 vaccine. Case Description/Methods: A 38-year-old female with a history of Helicobacter pylori treated with amoxicillin and pantoprazole three months ago and recent COVID-19 vaccination presented with two weeks of right upper quadrant pain and diarrhea. Patient received second dose of vaccination two weeks prior to symptom onset. Five days post-symptom onset, she developed a pruritic rash with vomiting and yellowing of her skin. Physical examination was notable for normal mentation, scleral icterus, jaundice, and a maculopapular rash. Initial blood workup showed international normalized ratio 2.4, alkaline phosphatase 212 U/L, ALT 3769 U/L, AST 1572 U/L and total bilirubin of 23.8 mg/ dL. Viral hepatitis serologies, chronic liver disease workup and autoimmune serologies were normal. Imaging demonstrated no intra- or extra-hepatic biliary ductal dilation. Liver biopsy showed portal inflammation with interface activity, diffuse lobular inflammation, and perivenulitis with abundant lymphocytes and plasma cells consistent with seronegative AIH or drug induced AIH. The patient developed altered mental status meeting the criteria of acute liver failure, she was started on corticosteroids as well as supportive care with resolution of encephalopathy and was discharged home on prednisone. Discussion: Several etiologies of drug-induced AIH are well-established, however cases secondary to COVID-19 vaccination have been minimally reported. Common adverse events for COVID-19 vaccination have been noted such as fever, chills, fatigue, headache, and muscle pain. Several rare side effects have occurred including immune thrombocytopenia and one other suspected case of Pfizer- BioNTech COVID-19 vaccination-induced AIH reported in the literature. In that case the patient developed symptoms within one week of the first dose. This case serves to report a potential association and not necessarily causation between the Pfizer-BioNTech COVID-19 vaccination and AIH.

Background Hepatitis C is a noteworthy public health issue around the globe, resulting in liver-related problems. The disease is caused Hepatitis C virus a positive sense RNA virus belongs to Flaviviridae family. Approximately 6% population of Pakistan is infected with HCV. Due to genetic variation, HCV is categorized into 7 genotypes and 67 subtypes. Methodology In this study total 1100 ICT positive samples were collected from December 2016 to May 2017 from Tehsil Dagger District Buner. RNA was extracted from ICT positive serum samples of 1100 patients and, were screened for HCV-RNA by using Reverse Transcriptase-Nested polymerase chain reaction (RT-nested PCR) and, then the positive samples were subjected for HCV genotyping. Statistical analysis was carried on SPSS version 10.0. Results Out of 1100 ICT positive samples, HCV RNA was detected in 375 individuals, of which 14.9% were males and, 19.2% females. The frequency of HCV genotypes Untypable was 43.5%), followed by 3a (29.6%), 3 b was 9.6%, 2a was 5.9%, 1a was 5.3%, 1 b (4.0%) and, 2 b was 1.9% in these patients. Both genotypes untypable and 3a were the most prevalent genotypes in patients of all age groups and its prevalence was found high among patients with increasing age (>30years). The prevalence rate of HCV in age of 21–30 years (30.1%), of 31–40 years the percentage of positive cases are 24.85% and 11–20 years of age group is (11.4%). Furthermore, genotypes untypable, 3a and 3 b were found to be the most common genotypes in patients with history of barber shops, dental surgery, and receiving multiple injections. Conclusion The current study reveals HCV untypable variants as the most frequent genotypes in the HCV patients of district Buner KP, Pakistan, with most patients in the age group 21–30 years. HCV various isolates were associated with different routes of transmission. The predominant factors of HCV included shaving in barber shops and intra-venous drugs use. These findings may suggest anti-HCV therapy and monitoring HCV infections.

Proton pump inhibitors (PPIs) are the mainstay of treatment for many gastric acid-related diseases with a relatively safe drug profile. One of the rare side effects is PPI-induced bullous pemphigoid. We describe a case of new-onset bullous pemphigoid on initiation of lansoprazole for esophagitis after a nationwide Zantac recall. This condition can improve with the cessation of PPI and the use of corticosteroids. However, it poses a significant challenge to the management of gastroesophageal reflux disease by limiting available pharmacologic options. In addition, this case highlights the negative effects of a drug recall.

© 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p

Key Clinical Message Symptoms associated with numerous diseases can be indistinguishable from those of the urinary system disorders because receptors of many visceral organs as well as the body wall transmit sensation through pain fibers shared with the kidneys. Disregarding important family background of genetic disorder can be detrimental for some patients.

The Hippo-signaling pathway is a mechanism implicated in cardiomyocyte cytoprotection and regeneration after a myocardial infarction. Yes-associated protein 1, the main effector protein of this pathway, acts as a co-transcriptional activator to promote cardiomyocyte proliferation and survival. However, the biological mechanisms by which yes-associated protein 1 protects the heart post-MI are currently unknown. Here, we propose that yes-associated protein 1 plays a critical role in cardiomyocyte cytoprotection after simulated ischemia-reperfusion injury. AC16 human cardiomyocytes were infected with lentiviral plasmids containing normal human yes-associated protein 1 and a constitutively active form of YAP, YAP1S127A. Cells were exposed to ischemia-reperfusion injury using a hypoxic chamber. Hippo-signaling characterization after ischemia-reperfusion injury was performed via Western blotting and reverse transcriptase polymerase chain reaction. Cell viability, apoptosis, and cellular hypertrophy were assessed as a measure of cytoprotection. The GSK3β inhibitor CHIR99021 was used to investigate cross-talk between Hippo and Wnt-signaling and their role in cytoprotection after ischemia-reperfusion-injury. Ischemia-reperfusion injury resulted in significant decreased expression of the non-phosphorylated Hippo signaling kinases MST1 and LATS1, along with decreased expression of YAP/TAZ. Overexpression of yes-associated protein 1 improved cellular viability, while reducing hypertrophy and apoptosis via the ATM/ATR DNA damage response pathway. Activation of β-catenin in YAP-infected cardiomyocytes synergistically reduced cellular hypertrophy after ischemia-reperfusion-injury. Our findings indicate that yes-associated protein 1 is cytoprotective in AC16 human cardiomyocytes after ischemia-reperfusion injury, which may be mediated by co-activation of the canonical Wnt/β-catenin pathway. Thus, activation of yes-associated protein 1 may be a novel therapeutic to repair the infarcted myocardium.Impact statementGenetically engineering the cells of the heart after myocardial infarction to display a more regenerative phenotype is a promising therapy for heart failure patients. Here, we support a regenerative role for yes-associated protein 1, the main effector protein of the Hippo signaling pathway, in AC16 human cardiomyocytes as a potential therapeutic gene target for cardiac repair after myocardial infarction.

We describe a unique case of rash and acute hepatitis confounded by the presence of syphilis that created suspicion for syphilitic hepatitis, a rare and often misdiagnosed condition. Investigation concerning the etiology alternatively lead to the diagnosis of 2 concomitant conditions: active autoimmune hepatitis and secondary syphilis. To our knowledge, this is the first description in the literature of the simultaneous occurrence of secondary syphilis and autoimmune hepatitis. This case serves to increase the recognition of the clinical characteristics and diagnostic challenges of syphilitic hepatitis and to discuss the potential role of pathogens in the induction of autoimmunity.

Primary hepatic neuroendocrine tumour is an exceedingly rare entity. We hereby delineate the case of a 45-year-old Balti descent woman who hails from a land-locked village situated in the foothills of the Pakistani Himalayas. The patient presented to our medical centre with a hepatic mass. She underwent extensive diagnostic workup. The consistent findings of an abdominal CT scan, coupled with her clinical history, insinuated a preoperative diagnosis of atypical hepatic haemangioma. After a detailed discussion in a multidisciplinary meeting, a standard right hemihepatectomy was performed. She had an uneventful postoperative recovery and was discharged in stable condition after 1 week. Surprisingly, pathological examination and immunohistochemistry of the resected specimen divulged the diagnosis of a grade II primary hepatic neuroendocrine tumour. Her somatostatin-receptor scintigraphy and Gallium-68 DOTATATE positron emission tomography scan excluded residual hepatic or additional body lesions. Regular follow-ups over the past 4 years demonstrated unremarkable radiological findings with no recurrence to date.

Background Acute myocardial infarction (MI) remains one of the leading causes of death worldwide with no curative therapy available. Stem cell therapies have been gaining interest as a means to repair the cardiac tissue after MI and prevent the onset of heart failure. Many in vivo reports suggest that the use of stem cells is promising, yet clinical trials suggest that the cells fail to integrate into the native tissue, resulting in limited improvements in cardiac function and repair. To battle this limitation, the combination of using stem cells embedded in a bioactive scaffold that promotes cell retention is growing in interest. Yet, a systematic review of the literature on the use of stem cells embedded in bioactive scaffolds for cardiac repair has not yet been performed. In this protocol, we outline a systematic review and meta-analysis of preclinical trials in animal MI models that utilize stem cell-embedded scaffolds for cardiac repair and compare their effects to stem cell-treated animals without the use of a scaffold. Methods/design We will search the following electronic databases: Cochrane Library, MEDLINE, Embase, PubMed, Scopus and Web of Science, and gray literature: Canadian Agency for Drugs and Technologies in Health and Google Scholar. We will only include randomly controlled preclinical trials that have directly investigated the effects of stem cells embedded in a scaffold for cardiac repair in an animal MI model. Two investigators will independently review each article included in the final analysis. The primary endpoint that will be investigated is left ventricular ejection fraction. Secondary endpoints will include infarct size, end systolic volume, end diastolic volume, fractional shortening and left ventricular wall thickness. Pooled analyses will be conducted using the DerSimonian-Laird random effects and Mantel-Haenszel fixed-effect models. Between-studies heterogeneity will be quantified and determined using the Tau2 and I2 statistics. Publication bias will be assessed using visual inspection of funnel plots and complemented by Begg’s and Egger’s statistical tests. Possible sources of heterogeneity will be assessed using subgroup-meta analysis and meta-regression. Discussion To date, the use of scaffolds in myocardial repair has not yet been systematically reviewed. The results of this meta-analysis will aid in determining the efficacy of stem cell-embedded scaffolds for cardiac repair and help bring this therapy to the clinic. Electronic supplementary material The online version of this article (10.1186/s13643-018-0845-z) contains supplementary material, which is available to authorized users.

Klebsiella pneumoniae is a common bacterial pathogen that is known to cause diverse community acquired and nosocomial infections [1,2]. These infections commonly occur in hospitalized individuals with impaired host defenses [3]. However the proportion of community acquired vs nosocomial infection has markedly increased in recent years [4]. A community acquired syndrome of cryptogenic invasive Klebsiella pneumoniae Liver Abscess Syndrome (CIKPLA) has been known to typically affect individuals of Southeast Asian origin, and is complicated by devastating septic spread to other organs [5]. We report a case of community acquired invasive Klebsiella pneumoniae infection with multi organ involvement in an individual of non-Asian origin. The aim of this case report is to alert clinicians about increasing prevalence of CIKPLA syndrome, its different clinical presentations and occurrence in different populations suggesting a need for increased vigilance for early diagnosis and prompt management to prevent disastrous sequelae.

Cardiovascular diseases remain the primary cause of death.1 Myocardial infarction (MI), angina, and stroke take >16 million lives every year, but the underlying mechanisms by which these often‐fatal cardiovascular events occur tend to escape attention.2 Atherosclerosis is the underlying pathological inflammatory vascular disease not only responsible for most MIs and strokes, but it accounts for 29% of deaths worldwide.1, 3 Once believed to be a passive process, it is now understood that atherosclerosis takes an active route involving several cell types, with contributions from a multitude of organ systems, molecular mechanisms, and other pathological conditions, including, but not limited to, hypertension, hyperlipidemia, and type 2 diabetes mellitus.1, 3, 4, 5 Atherosclerosis is characterized by the accumulation of lipids, fibrous elements, and inflammatory cells within the vascular wall of medium and large muscular and elastic arteries.1, 3, 6 Atherosclerotic plaque formation leads to intimal thickening and luminal stenosis.1 Reduction of blood flow ensues, leading to ischemia of the brain, heart, and extremities and clinically manifesting as MI, angina, or stroke. The main features of atherosclerosis are endothelial dysfunction, intimal thickening, inflammation, and vascular calcification (VC).4, 7, 8 These processes are considered a consequence to vascular injury.1 VC is characterized by calcium deposition in the walls of the vasculature.5 Expansion of the calcified lesion leads to thrombus formation and, if significant enough, vascular occlusion. Although the exact mechanisms for VC are unknown, there has been an increase in interest about the role Wingless (Wnt) signaling plays in disease pathogenesis. Briefly, the Wnt signaling pathway is an evolutionarily conserved pathway across kingdom Animalia and plays a crucial role in pattern formation during embryogenesis.9 The Wnt signal transduction pathway plays a crucial role in organ formation in embryonic development, cell proliferation, polarity, migration, and differentiation.10 Thus, deregulated Wnt signaling is associated with many human diseases.11 Therefore, it is justifiable to suggest that research delineating atherogenesis, with focus on the contribution of Wnt signaling in the pathogenesis of atherosclerotic calcification, is warranted.

With the absence of a curative therapy, novel strategies to combat heart failure are urgently required. As an intriguing approach to restore the necrotic cardiac tissue, stem cell regenerative therapy has been broadly assessed. Recently, the placenta emerged as a unique stem cell source that is abundant and nonimmunogenic and shares many properties with adult and embryonic stem cells. Numerous stem cell populations can be isolated and identified within the placental layers. In this chapter, we have summarized the cardiomyogenic potential of placenta-derived stem cells addressed in vitro and in animal model studies. The exceptional properties of these cells, such as the expression of cardiac-specific markers and transcriptional factors, along with their lack of ethical conflicts and young age have shed the light on the placenta-derived stem cells as an appealing source that could mitigate ventricular remodeling and promote cardiac healing.

The cellular mechanisms that induce calcific aortic stenosis are yet to be unraveled. Wnt signaling is increasingly being considered as a major player in the disease process. However, the presence of Wnt Frizzled (Fzd) receptors and co-receptors LRP5 and 6 in normal and diseased human aortic valves remains to be elucidated. Immunohistochemistry and quantitative polymerase chain reaction were used to determine Fzd receptor expression in normal and calcified human aortic valve tissue, as well as human aortic valve interstitial cells (HAVICs) isolated from calcified and normal human aortic valves. There was significantly higher mRNA expression of 4 out of the 10 Fzd receptors in calcified aortic valve tissues and 8 out of the 10 in HAVICs, and both LRP5/6 co-receptors in calcified aortic valves (P < 0.05). These results were confirmed by immunohistochemistry, which revealed abundant increase in immunoreactivity for Fzd3, 7, and 8, mainly in areas of lipid core and calcified nodules of diseased aortic valves. The findings of abundant expression of Fzd and LRP5/6 receptors in diseased aortic valves suggests a potential role for both canonical and noncanonical Wnt signaling in the pathogenesis of human aortic valve calcification. Future investigations aimed at targeting these molecules may provide potential therapies for aortic valve stenosis.

Background: Geographical distributional of gastric cancer (GC), differences in stage at the time of presentation and varying surgical expertise have resulted in different management strategies around the world. The aim of this study is to determine postoperative morbidity/mortality and overall survival in patients with GC treated at a cancer hospital in Pakistan. Patients and Methods: A retrospective review of patients who underwent surgical resection with curative intent for GC from June 2006 to July 2012 was performed. Primary end point was overall survival after a minimum follow-up of 15 months. For categorical data, frequencies were calculated, and means were measured for continuous variables. Chi-square test was used to compare categorical data and Kaplan–Meir survival analysis was performed to estimate 5 years survival outcome using SPSS. Results: Majority of the patients were males with median age of 51 years. Perioperative chemotherapy was offered to 75 patients while upfront surgery was performed in 23 patients. In perioperative chemotherapy group 51 patients and 22 in the upfront surgery group ended up having curative resection. The 5 years survival (n = 98) was found to be of 37%. The 5 years survival of patients in perioperative chemotherapy group (n = 75) was 44% while those who had a curative resection (n = 73) had survival of 46%. Conclusion: Gastric adenocarcinoma is an aggressive disease. Perioperative chemotherapy works well in Pakistani population as the results at our institution are comparable with international data.

Use of metformin throughout pregnancy in women with polycystic ovary syndrome (PCOS) has shown to reduce the rates of early pregnancy loss, preterm labor, and prevention of fetal growth restriction. Metformin has been shown to have encouraging effects on several metabolic aspects of polycystic ovarian syndrome, such as insulin sensitivity, plasma glucose concentration and lipid profile and since women with PCOS are more likely than healthy women to suffer from pregnancy-related problems like early pregnancy loss, gestational diabetes mellitus and hypertensive states in pregnancy, the use of metformin therapy in these patients throughout pregnancy may have beneficial effects on early pregnancy loss and development of gestational diabetes.

Retrospective review of a case series.To present the clinical characteristics and treatment of spinal deformity in DiGeorge syndrome.There are no data on the development of spinal deformity in this condition. A high rate of wound infection could be expected after spinal surgery due to congenital thymic hypoplasia.The medical records and spinal radiographs of 4 consecutive patients were reviewed. All patients were followed for a minimum of 2.5 years after spinal surgery.The mean age at diagnosis of spinal deformity was 9.9 years. The type of deformity was not uniform but the curves progressed in all patients requiring a spinal arthrodesis at a mean age of 16.1 years. Two patients developed a thoracolumbar scoliosis and underwent an anterior spinal arthrodesis with instrumentation, which produced a good outcome. The remaining 2 patients developed a double thoracic and lumbar scoliosis with increased thoracic kyphosis. Brace treatment was unsuccessful to control the deformity in one of these patients. Both patients underwent a posterior spinal arthrodesis with segmental instrumentation, which achieved satisfactory correction of the scoliosis with no loss of correction or detected pseudarthrosis at follow-up. However, both patients developed junctional kyphosis above the proximal end of the instrumentation. This was asymptomatic and nonprogressive; therefore, cephalad extension of the fusion was not required. Irradiated blood products were administered in all patients to prevent graft-versus-host disease. The postoperative course was uncomplicated and none of the patients developed wound healing problems or infections.The development of spinal deformity in patients with DiGeorge syndrome may be associated to the presence of marked ligamentous laxity and congenital cardiac disease. There is significant variability on the pattern of spinal deformity, which in our series was progressive in all patients and required surgical correction with no perioperative complications.

Undisplaced fractures of both the diaphysis and the lateral end of the clavicle have a high rate of union, and the functional outcomes are good after nonoperative treatment. Nonoperative treatment of displaced shaft fractures may be associated with a higher rate of nonunion and functional deficits than previously reported. However, it remains difficult to predict which patients will have these complications. Since a satisfactory functional outcome may be obtained after operative treatment of a clavicular nonunion or malunion, there is currently considerable debate about the benefits of primary operative treatment of these injuries. Displaced lateral-end fractures have a higher risk of nonunion after nonoperative treatment than do shaft fractures. However, nonunion is difficult to predict and may be asymptomatic in elderly individuals. The results of operative treatment are more unpredictable than they are for shaft fractures.

Diets rich in fruits and vegetables reduce risk of adverse cardiovascular events. However, the constituents responsible for this effect have not been well established. Lately, the attention has been brought to vegetables with high nitrate content with evidence that this might represent a source of vasoprotective nitric oxide. We hypothesized that short-term consumption of spinach, a vegetable having high dietary nitrate content, can affect the arterial waveform indicative of arterial stiffness, as well as central and peripheral blood pressure (BP). Using a placebo-controlled, crossover design, 27 healthy participants were randomly assigned to receive either a high-nitrate (spinach; 845 mg nitrate/day) or low-nitrate soup (asparagus; 0.6 mg nitrate/day) for 7 days with a 1-week washout period. On days 1 and 7, profiles of augmentation index, central, and brachial BP were obtained over 180 min post-consumption in 4 fasted visits. A postprandial reduction in augmentation index was observed at 180 min on high-nitrate compared to low-nitrate intervention (-6.54 ± 9.7% vs. -0.82 ± 8.0%, p = 0.01) on Day 1, and from baseline on Day 7 (-6.93 ± 8.7%, p < 0.001; high vs. low: -2.28 ± 12.5%, p = 0.35), suggesting that the nitrate intervention is not associated with the development of tolerance for at least 7 days of continued supplementation. High vs. low-nitrate intervention also reduced central systolic (-3.39 ± 5.6 mmHg, p = 0.004) and diastolic BP (-2.60 ± 5.8 mmHg, p = 0.028) and brachial systolic BP (-3.48 ± 7.4 mmHg, p = 0.022) at 180 min following 7-day supplementation only. These findings suggest that dietary nitrate from spinach may contribute to beneficial hemodynamic effects of vegetable-rich diets and highlights the potential of developing a targeted dietary approach in the management of elevated BP.

Objective: The rate of recurrence in high grade non muscle invasive bladder cancer (NMIBC) is 70% with progression rate of 15-40% at 5 years. The treatment of high grade NMIBC is intravesical BCG therapy, however for high risk cases radical cystectomy is recommended. In this study we determined the response of high grade NMIBC to BCG therapy and the factors affecting it in south Asian population. Methods: This retrospective cohort study was conducted on 64 patients treated with intravesical BCG for high grade NMIBC from Dec 2008 to July 2012. Smoking, tumor size, location and multiplicity were taken as prognostic factors. Recurrence and progression were determined by cystoscopy and upper tract imaging according to European Association of Urology guidelines. The association of prognostic factors with recurrence and progression was determined. Results: The rate of recurrence and progression was found to 45.8% and 27.1% respectively after a mean follow up 28.36 months. Smokers had 4 times greater odds of progression of tumor as compared to nonsmokers. Patients with large tumors had 6.7 times greater odds of progression as compared to patients with small tumors. Conclusion: Smokers with large and multiple high grade NMIBC constitute the high risk group. These patients may be offered early radical cystectomy and advised to stop smoking.