Predictors of recurrence and long-term patient reported outcomes following surgical repair of anal fistula, a retrospective analysis.

PURPOSE: Surgery for anal fistulas can result in devastating complications, including reoperations and fecal incontinence. There is limited contemporary evidence comparing outcomes since the adoption of the ligation of intersphincteric fistula tract procedure into mainstream practice. The purpose of this study is to compare recurrence rates and long-term outcomes of anal fistula following repair. METHODS: Data was collected from the electronic medical records or patient reported outcomes from patients aged 18 or older with a primary or recurrent cryptoglandular anal fistula. Primary outcome was recurrence defined as the identification of at least one fistula os or a high clinical suspicion of anal fistula. Secondary outcomes included fecal incontinence and postoperative quality of life. RESULTS: A total of 171 patients underwent definitive surgical repairs for their anal fistula. So 66.5% had a simple fistula, and 33.5% had a complex fistula. Of the 171 patients, 12.5% had a recurrence. The recurrence rates were 5.9% for simple fistula and 25.4% for complex fistula. Predictors of recurrence included diabetes mellitus, history of anorectal abscess, complex fistula, and sphincter sparing surgery. LIFT or plug/biologic procedures were both associated with a 50% or greater recurrence rate. No significant differences were found in fecal incontinence or associated quality of life between sphincter sparing or non-sphincter sparing surgical resections. CONCLUSION: The study provides insights into the long-term outcomes of surgical repair for anal fistula. We demonstrate that sphincter sparing operations are associated with increased recurrence, meanwhile, non-sphincter sparing surgeries did not increase the risk of fecal incontinence or worsen quality of life.

Cyclic GMP-AMP synthase contributes to epithelial homeostasis in intestinal inflammation via Beclin-1-mediated autophagy.

Inflammatory bowel disease (IBD) represents a set of idiopathic and chronic inflammatory diseases of the gastrointestinal tract. Central to the pathogenesis of IBD is a dysregulation of normal intestinal epithelial homeostasis. cGAS is a DNA-sensing receptor demonstrated to promote autophagy, a mechanism that removes dysfunctional cellular components. Beclin-1 is a crucial protein involved in the initiation of autophagy. We hypothesized that cGAS plays a key role in intestinal homeostasis by upregulating Beclin-1-mediated autophagy. We evaluated intestinal cGAS levels in humans with IBD and in murine colonic tissue after performing a 2% dextran sulfate sodium (DSS) colitis model. Autophagy and cell death mechanisms were studied in cGAS KO and WT mice via qPCR, WB analysis, H&E, IF, and TUNEL staining. Autophagy was measured in stimulated intestinal epithelial cells (IECs) via WB analysis. Our data demonstrates cGAS to be upregulated during human and murine colitis. Furthermore, cGAS deficiency leads to worsened colitis and decreased levels of autophagy proteins including Beclin-1 and LC3-II. Co-IP demonstrates a direct binding between cGAS and Beclin-1 in IECs. Transfection of cGAS in stimulated HCT-116 cells leads to increased autophagy. IECs isolated from cGAS KO have diminished autophagic flux. cGAS KO mice subjected to DSS have increased cell death and cleaved caspase-3. Lastly, treatment of cGAS KO mice with rapamycin decreased the severity of colitis. Our data suggest that cGAS maintains intestinal epithelial homeostasis during human IBD and murine colitis by upregulating Beclin-1-mediated autophagy and preventing IEC death. Rescue of autophagy can attenuate the severity of colitis associated with cGAS deficiency.

Patient Factors Limit Colon Cancer Survival at Safety-Net Hospitals: A National Analysis.

BACKGROUND: Safety-net hospitals serve a vital role in society by providing care for vulnerable populations. Existing data regarding oncologic outcomes of patients with colon cancer treated at safety-net hospitals are limited and variable. The objective of this study was to delineate disparities in treatment and outcomes for patients with colon cancer treated at safety-net hospitals. METHODS: This retrospective cohort study identified 802,304 adult patients with colon adenocarcinoma from the National Cancer Database between 2004-2016. Patients were stratified according to safety-net burden of the treating hospital as previously described. Patient, tumor, facility, and treatment characteristics were compared between groups as were operative and short-term outcomes. Cox proportional hazards regression was utilized to compare overall survival between patients treated at high, medium, and low burden hospitals. RESULTS: Patients treated at safety-net hospitals were demographically distinct and presented with more advanced disease. They were also less likely to receive surgery, adjuvant chemotherapy, negative resection margins, adequate lymphadenectomy, or a minimally invasive operative approach. On multivariate analysis adjusting for patient and tumor characteristics, survival was inferior for patients at safety-net hospitals, even for those with stage 0 (in situ) disease. CONCLUSION: This analysis revealed inferior survival for patients with colon cancer treated at safety-net hospitals, including those without invasive cancer. These findings suggest that unmeasured population differences may confound analyses and affect survival more than provider or treatment disparities.

Medicaid expansion and the management of pancreatic cancer.

BACKGROUND: Medicaid expansion under the Affordable Care Act has improved access to screening and treatment for certain cancers. It is unclear how this policy has affected the diagnosis and management of pancreatic cancer. METHODS: Using a quasi-experimental difference-in-differences (DID) approach, we analyzed Medicaid and uninsured patients in the National Cancer Data Base during two time periods: pre-expansion (2011-2012) and postexpansion (2015-2016). We investigated changes in cancer staging, treatment decisions, and surgical outcomes. RESULTS: In this national cohort, pancreatic cancer patients in expansion states had increased Medicaid coverage relative to those in nonexpansion states (DID = 17.49, p < 0.01). Medicaid expansion also led to an increase in early-stage diagnoses (Stage I/II, DID = 4.71, p = 0.03), higher comorbidity scores among surgical patients (Charlson/Deyo score 0: DID = -13.69, p = 0.02), a trend toward more neoadjuvant radiation (DID = 6.15, p = 0.06), and more positive margins (DID = 11.69, p = 0.02). There were no differences in rates of surgery, postoperative outcomes, or overall survival. CONCLUSION: Medicaid expansion was associated with improved insurance coverage and earlier stage diagnoses for Medicaid and uninsured pancreatic cancer patients, but similar surgical outcomes and overall survival. These findings highlight both the benefits of Medicaid expansion and the potential limitations of policy change to improve outcomes for such an aggressive malignancy.

An Evidence-Based Care Protocol Improves Outcomes and Decreases Cost in Pediatric Appendicitis.

BACKGROUND: Appendicitis is a common indication for urgent abdominal surgery in the pediatric population. The postoperative management varies significantly in time to discharge and cost of care. The objective of this study was to investigate whether implementation of an evidence-based protocol after an appendectomy would lead to decreased length of stay and cost of care. METHODS: In 2014 at the Children's Hospital of Pittsburgh, an initiative to develop an evidenced-based protocol to treat appendicitis was undertaken. A work group was formed of pediatric surgeons and other important personnel to determine best practices. Treatment pathways were created. Pathways differed with recommendation on postoperative antibiotic choice and duration, diet initiation, and discharge criteria. Data were prospectively gathered from all patients (ages 0-18 y) with acute appendicitis from January 2015 to December 2016. Primary outcomes were length of stay and cost of care. Secondary outcomes were surgical site infection, readmission rate, and duration of postoperative antibiotics. RESULTS: Among the 1289 patients, 481 patients were in the preprotocol cohort and 808 patients were in the postprotocol cohort. 27% of patients had an intraoperative diagnosis of complicated appendicitis. There was a significantly shorter length of stay in the postprotocol cohort (P < 0.001). Median costs for the whole cohort decreased 0.6% and 24.6% for patients with complicated appendicitis after protocol initiation (P < 0.01). CONCLUSIONS: This study has demonstrated that introduction of an evidence-based clinical care protocol for pediatric patients with appendicitis leads to shorter hospital stay and decreased hospital costs.

Long-Term and Oncologic Outcomes of Robotic Versus Laparoscopic Liver Resection for Metastatic Colorectal Cancer: A Multicenter, Propensity Score Matching Analysis.

BACKGROUND: To assess long-term oncologic outcomes of robotic-assisted liver resection (RLR) for colorectal cancer (CRC) metastases as compared to a propensity-matched cohort of laparoscopic liver resections (LLR). Although safety and short-term outcomes of RLR have been described and previously compared to LLR, long-term and oncologic data are lacking. METHODS: A retrospective study was performed of all patients who underwent RLR and LLR for CRC metastases at six high-volume centers in the USA and Europe between 2002 and 2017. Propensity matching was used to match baseline characteristics between the two groups. Data were analyzed with a focus on postoperative and oncologic outcomes, as well as long-term recurrence and survival. RESULTS: RLR was performed in 115 patients, and 514 patients underwent LLR. Following propensity matching 115 patients in each cohort were compared. Perioperative outcomes including mortality, morbidity, reoperation, readmission, intensive care requirement, length-of-stay and margin status were not statistically different. Both prematching and postmatching analyses demonstrated similar overall survival (OS) and disease-free survival (DFS) between RLR and LLR at 5 years (61 vs. 60% OS, p = 0.87, and 38 vs. 31% DFS, p = 0.25, prematching; 61 vs. 60% OS, p = 0.78, and 38 vs. 44% DFS, p = 0.62, postmatching). CONCLUSIONS: Propensity score matching with a large, multicenter database demonstrates that RLR for colorectal metastases is feasible and safe, with perioperative and long-term oncologic outcomes and survival that are largely comparable to LLR.

Long-Term Oncologic Outcomes Following Robotic Liver Resections for Primary Hepatobiliary Malignancies: A Multicenter Study.

OBJECTIVE: Robotic liver surgery (RLS) has emerged as a feasible alternative to laparoscopic or open resections with comparable perioperative outcomes. Little is known about the oncologic adequacy of RLS. The purpose of this study was to investigate the long-term oncologic outcomes for patients undergoing RLS for primary hepatobiliary malignancies. METHODS: We performed an international, multicenter, retrospective study of patients who underwent RLS for hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), or gallbladder cancer (GBC) between 2006 and 2016. Age, gender, histology, resection margin status, extent of surgical resection, disease-free survival (DFS), and overall survival (OS) were retrospectively collected and analyzed. RESULTS: Of the 61 included patients, 34 (56%) had RLS performed for HCC, 16 (26%) for CC, and 11 (18%) for GBC. The majority of resections were nonanatomical or segmental resections (39.3%), followed by central hepatectomy (18%), left-lateral sectionectomy (14.8%), left hepatectomy (13.1%), right hepatectomy (13.1%), and right posterior segmentectomy (1.6%). R0 resection was achieved in 94% of HCC, 68% of CC, and 81.8% of GBC patients. Median hospital stay was 5 days, and conversion to open surgery was needed in seven patients (11.5%). Grade III-IV Dindo-Clavien complications occurred in seven patients with no perioperative mortality. Median follow-up was 75 months (95% confidence interval 36-113), and 5-year OS and DFS were 56 and 38%, respectively. When stratified by tumor type, 3-year OS was 90% for HCC, 65% for GBC, and 49% for CC (p = 0.01). CONCLUSIONS: RLS can be performed for primary hepatobiliary malignancies with long-term oncologic outcomes comparable to published open and laparoscopic data.

Raman and Infrared Studies of Platinum-Based Drugs: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, and Heptaplatin.

This study reports the optimized structures and lowest-energy conformations/stereochemistry of five currently used platinum-based drugs: cisplatin, carboplatin, nedaplatin, oxaliplatin, and heptaplatin. Normal Raman and IR spectra of each drug are experimentally obtained and have been compared to various levels of density functional theory (DFT). Although some combination of structure, reactivity, or spectroscopy for these drugs has been studied by various groups, there are no known experimental normal Raman and IR spectra for nedaplatin, oxaliplatin, and heptaplatin in the literature. The detailed structural and vibration findings of these drugs are very important to understanding platinum behavior and drug dynamics. The following work explores the vibrational frequencies of these drugs particularly by focusing on the low-energy modes between 200 and 600 cm-1, where anharmonicity effects will have less influence on the accuracy of computed frequencies. Ideally, the Pt-N stretching modes provide vibrational diagnostics for each drug. Interestingly, a vibrational energy decomposition analysis (VEDA) suggests that oxaliplatin and heptaplatin Pt-N stretching modes are not Raman or IR active. Instead, C-C and Pt-O stretching frequencies in the various bidentate dioxo ligands might be more useful in characterizing new cisplatin derivatives. Analysis of anharmonicity effects was compared against (and in tandem with) dimer computations of four of the five drugs. Harmonic vibrational computations of the dimeric cisplatin derivatives provided greater qualitative improvement than that of the monomeric derivatives. Satisfying agreement with experimental Raman spectra was obtained, even without resorting to linear scale factors for the harmonic dimer frequencies.

Papillary lesions of the breast: To excise or observe?

Papillary lesions of the breast range from benign to atypical to malignant. Although papillomas without frank cancer are benign, their management remains controversial. When a core needle biopsy of a lesion yields a diagnosis of intraductal papilloma with atypia, excision is generally recommended to rule out a concurrent malignant neoplasm. For intraductal papillomas without atypia, however, recommendations for excision versus observation are variable. The aims of this study are to evaluate the rate of concurrent malignancies for intraductal papilloma diagnosed on core needle biopsy and to assess the long-term risk of developing cancer after the diagnosis of a papillary lesion. This single institution retrospective study analyzed 259 patients that were diagnosed with intraductal papilloma (IDP) by core needle biopsy from 1995 to 2010. Patients were grouped by initial diagnosis into three groups (papilloma without atypia, papilloma with atypia, and papilloma with atypical duct hyperplasia or atypical lobular hyperplasia (ADH/ALH) and followed up for long-term outcomes. After a core needle biopsy showing IDP with atypia or IDP + ADH/ALH, surgical excision yielded a diagnosis of concomitant invasive or ductal in situ cancer in greater that 30% of cases. For intraductal papilloma without atypia, the likelihood of cancer was much lower. Moreover, even with excision, the finding of intraductal papilloma with atypia carries a significant risk of developing cancer long-term, and such patients should be followed carefully and perhaps should be considered for chemoprevention.

Laparoscopic liver resection for hepatocellular carcinoma in early and advanced cirrhosis.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma is well described in early cirrhosis. Less is known regarding outcomes with more advanced cirrhosis, and this study aimed to compare these groups. METHODS: A retrospective review of resections at a high-volume hepatobiliary center over a 15-year period was performed. Primary end-points were 30 and 90-day mortality. Secondary end-points included complications and survival. RESULTS: 80 early (Child's A) were compared to 26 advanced (20 Child's B and 6 Child's C) patients. Baseline patient and tumor characteristics were similar except for parameters indicating degree of cirrhosis. Only early cirrhotic patients underwent anatomic hepatectomies (six cases) and median operative times were longer (151 vs 99 min, p = 0.03). Intraoperative blood loss, conversion, R0 resection, length-of-stay and perioperative complications were comparable. 30 and 90-day mortality were statistically similar (2.5 vs 0%, OR 1.69, 95% CI 0.08-36.19 and 2.5 vs 7.7%, OR 0.31 95% CI 0.04-2.30). There was a trend toward longer survival in the early cirrhotic group but this did not reach significance (50 vs 21 months, p = 0.077). CONCLUSIONS: In carefully selected advanced cirrhotic patients, laparoscopic liver resection may be performed with acceptable outcomes. Though this is not yet well established, further trials may be warranted.

Readmission After Surgical Resection and Transplantation for Hepatocellular Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Liver resections and transplantations have increasingly become feasible options for potential cure. These complex surgeries are inherently associated with increased rates of readmission. In the meanwhile, hospital readmission rates are rapidly becoming an important quality of care metric. Therefore, it is very important to understand the effect of 30-day readmission on mortality and the factors associated with increased 30- and 90-day mortality rates. METHODS: This is a retrospective cohort study utilizing data from the National Cancer Database. Patients included were 18 years or older who underwent liver resection or liver transplantation for HCC between 2003 and 2011. Our primary outcomes of interest were 30- and 90-day mortality rates. Our primary independent variable of interest was 30-day readmission. RESULTS: 16 658 patients underwent either a liver resection or transplantation for HCC between 2003 and 2011. For patients with liver transplantations, increased readmission rates were associated with lower risks of 30-day mortality (P = .012) but a trend toward higher 90-day mortality (P = .057). Patients who underwent liver resection for HCC also demonstrated increased readmission rates to be associated with lower risk of 30-day mortality (P = .014) but higher 90-day mortality (P ≤ .001). CONCLUSION: This is the only study to utilize a national database to investigate the association between readmission rates and mortality rates of both liver transplantations and resections for patients with HCC. We demonstrate 30-day readmission to show no increase in 30-day mortality, but rather higher 90-day mortality.

Readmission After Surgical Resection for Colon and Rectal Cancers: A Retrospective Cohort Study.

BACKGROUND: Colorectal adenocarcinoma is a leading cause of cancer mortality worldwide, often requiring patients to undergo anatomy-altering surgical interventions leading to increased postoperative readmission. Hospital readmission rates have been correlated with increased mortality. Therefore, it is important to understand the association between 30-day readmission rates and mortality as well as the factors associated with increased readmission rates. STUDY DESIGN: This is a retrospective review utilizing data from the National Cancer Database. Our primary outcomes of interest were 30- and 90-day mortality rates. Our primary independent variable of interest was 30-day readmission. RESULTS: Between 2010 and 2016, 207 299 patients underwent surgery for rectal cancer and 754 895 for colon cancer. The readmission rates within 30 days of discharge were 5.4% and 5.5% for patients after surgery for rectal or colon cancer, respectively. 30-day readmission was not associated with 30-day mortality, but it was independently associated with increased 90-day mortality and inferior long-term survival for both cohorts (P = .001). Independent risk factors significantly associated with increased readmission included race, non-private insurance, and low income. CONCLUSION: This study provides a large, up-to-date, and comprehensive analysis of readmission rates for colon and rectal cancers. We demonstrate that socioeconomic factors are associated with increased 30-day readmission. 30-day readmission is also independently associated with increased 90-day mortality as well as lower overall survival rates. Our study supports the need for implementation of programs that support patients of lower socioeconomic status undergoing surgery to further decrease readmission rates and mortality.

Search for safer and potent natural inhibitors of Parkinson's disease.

After Alzheimer's disease, Parkinson's disease (PD) has taken second place in becoming one of the most commonly occurring neurological diseases being responsible for a number of disabling motor symptoms ranging from bradykinesia, akinesia, tremors to rigidity, that mostly targets the elderly population and severely disrupts their quality of life. The true underlying pathology of PD yet remains a mystery, however, recent advances in the field have pointed towards the production of α-synuclein aggregates, oxidative stress, and an imbalance between levels of acetylcholine and dopamine neurotransmitters in the brain that have been shown to result in loss of coordinated movement. Current treatments of PD include the gold standard dopamine precursor L-dopa, dopamine agonists pergolide and bromocriptine, catechol-o-methyl transferases inhibitors, entacapone and tolcapone and monoamine oxidase inhibitors such as Selegine and Rasagiline amongst several other drugs. While these drugs are successful in treating motor symptoms of the disease, they do so with a plethora of side effects that are especially debilitating to the elderly. In the recent years, a considerable amount of attention has been shifted towards phytocompounds such as flavonoids and green tea catechins due to promising experimental results. In this review, we have compiled phytocompounds that have shown potent activity against some of the most important targets for antiparkinsonian therapy. These compounds have exhibited activities that transcend the limits of simply attenuating mitochondrial oxidative stress and have opened doors to the discovery of novel lead compounds for newer, efficacious antiparkinsonian therapies with wider therapeutic windows.

Pathologic Complete Response Following Neoadjuvant Therapy for Gastric Adenocarcinoma: A National Cancer Database Analysis on Incidence, Predictors, and Outcomes.

INTRODUCTION: With advances in multimodal therapy, survival rates in gastric cancer have significantly improved over the last two decades. Neoadjuvant therapy increases the likelihood of achieving negative margins and may even lead to pathologic complete response (pCR). However, the impact of pCR on survival in gastric cancer has been poorly described. We analyzed the rate and predictors of pCR in patients receiving neoadjuvant therapy as well as impact of pCR on survival. METHODS: We conducted a National Cancer Database (NCDB) analysis (2004-2016) of patients with gastric adenocarcinoma who received neoadjuvant chemotherapy followed by surgical resection. RESULTS: The pCR rate was 2.2%. Following adjustment, only neoadjuvant chemoradiation, non-signet histology, and tumor grade remained as significant factors predicting pCR. pCR was a statistically significant predictor of survival. CONCLUSION: In this NCDB study, pCR was a predictor of survival. Though chemoradiation rather than chemotherapy alone was a predictor of pCR, it was not a predictor of survival. Further studies are needed to elucidate the role of radiation in the neoadjuvant setting and to discern the impact of pCR on survival.

Association Between Helicobacter pylori Infection and Serum Iron Profile.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is reported to be the most frequent cause of morbidity and mortality in cases of upper gastrointestinal (GI) diseases. There is paucity of research between the possible association of H. pylori and iron stores and iron deficiency anemia (IDA). In this study, we will determine if there is an association between serum total iron-binding capacity (TIBC), serum iron and ferritin levels, and H. pylori infection. METHODS: This case-control study was conducted in the gastroenterology ward of a major hospital in Pakistan from December 2020 to April 2021. Three hundred patients diagnosed with H. pylori were enrolled along with 300 participants in the control group. H. pylori was confirmed or excluded with the help of Giemsa stained gastric biopsy specimens. Blood was sent to the laboratory to test for ferritin, serum iron, and TIBC. Each sample was drawn in the morning to avoid any fluctuations. RESULTS: The mean serum iron level was significantly lower in participants with H. pylori infection compared to those who did not have H. pylori infection (110.72 ± 28.38 ug/dL vs. 162.5 ± 21.18 ug/dL; p-value: <0.0001). Serum ferritin level was significantly higher in participants with H. pylori infection (536.82 ± 117.0 ng/dL vs. 391.31 ± 101.54 ng/dL; p-value: <0.0001). CONCLUSION:  In comparison with the control group, TIBC and serum iron levels were found to be lower in the case group.

Frequency of Cutaneous Disorders in Patients With Celiac Disease.

Background and objective Celiac disease is an autoimmune multisystem disorder that is triggered by dietary gluten sensitivity in genetically susceptible individuals. It presents with extraintestinal cutaneous manifestations including dermatitis herpetiformis (DH), atopic dermatitis, psoriasis, urticaria, and alopecia areata. Due to the insufficient availability of data, this study aimed to estimate the frequency of cutaneous manifestation in a Pakistani population with celiac disease. Methods This cross-sectional study was conducted from January 2020 to July 2021, and 300 patients with a confirmed diagnosis of celiac disease were enrolled in the study from the internal medicine department of a tertiary care hospital in Pakistan. Celiac disease was confirmed by the presence of immunoglobulin A (IgA) endomysial antibody and IgA tissue transglutaminase antibody. The presence of cutaneous manifestations was assessed with the assistance of a qualified dermatologist and noted in a self-structured questionnaire. Results Overall, the most common cutaneous manifestation was DH (16.0%), whereas the second most common cutaneous manifestation was psoriasis (13.8%). DH was most commonly found among males (18.9%), while psoriasis was more common among females (14.12%). Conclusion Among the various cutaneous presentations in patients with celiac disease, the most common dermatological manifestation was DH. Therefore, patients with cutaneous manifestations should undergo screening for celiac disease.

Comparison of Effect of Nebivolol and Bisoprolol on Sexual Function of Hypertensive Female Patients.

Introduction Male and female sexual dysfunction is frequently found in patients with hypertension. Many studies indicate that this is found more frequently in patients treated with beta-blockers rather than due to hypertension itself; however, almost all studies have been done on male population. This study aims to study the effect of two commonly used beta-blockers on sexual function of a hypertensive female patient. Methods This two-arm open-label randomized prospective study was conducted from April 1, 2019 to March 30, 2020 in a tertiary care hospital at Pakistan. One hundred and fifty participants randomized to group A were given nebivolol 5 mg once daily in addition to their current hypertensive treatment. Another 150 participants randomized to group B were given bisoprolol 5 mg once daily in addition to their hypertensive therapy. Sexual function was assessed on day 0 and day 90 using female sexual function index (FSFI). Results The mean sexual score in the nebivolol group significantly improved after day 90 in comparison to day 0 (24.16 ± 2.1 vs. 26.91 ± 2.6; p-value < 0.0001), while no difference in sexual score in bisoprolol group after day 90 was observed (24.14 ± 2.1 vs. 24.12 ± 2.0; p-value = 0.91). Conclusion In this study, nebivolol group was associated with a significant improvement in sexual function. This can be due to additional vasodilation properties and a low risk of sexual side effects associated with nebivolol.

Impact of Intravenous Vitamin C Administration in Reducing Severity of Symptoms in Breast Cancer Patients During Treatment.

Introduction Alternative medicine during treatment is often used to make the quality of life (QoL) better. Women with early-stage breast cancer, particularly the ones who possess lower QoL, are more prone to opt for complementary medicine. This study aims to explore the effects exerted by intravenous vitamin C (IVC) on symptoms and adverse events associated with breast cancer treatment. Methods This single-center, parallel-group, single-blind interventional study was conducted in the oncology ward of a tertiary care hospital in Pakistan. For this study, after informed consent was taken, breast cancer patients with Union for International Cancer Control stages IIA to IIIb were included in the study. Three hundred and fifty (n = 350) patients were randomized into two groups at a ratio of 1:1. Study group was randomized to receive 25 grams per week of IVC at a rate of 15 grams per hour for four weeks in addition to their current standard treatment, and the control group received placebo (normal saline drip with label removed) in addition to their current standard treatment. Results In patients who had received IVC, there was a significant decrease in the mean severity score after 28 days for the following symptoms: nausea (2.65 ± 0.62 vs. 2.59 ± 0.68; p-value: 0.0003), loss of appetite (2.26 ± 0.51 vs. 2.11 ± 0.52; p-value: 0.007), tumor pain (2.22 ± 0.45 vs. 1.99 ± 0.40, p-value: <0.0001), fatigue (3.11 ± 0.32 vs. 2.87 ± 0.29; p-value: <0.0001), and insomnia (2.59 ± 0.35 vs. 2.32 ± 0.36, p-value: <0.0001). Conclusion Our study showed improvement in the mean severity score of nausea, fatigue, tumor pain, loss of appetite, and fatigue. More studies are also needed to assess the long-term effects of IVC in the cancer management. This shall help incorporate the use of IVC in standard practice to make the journey of cancer management comfortable for the patients.

Estimation of polymorphisms in the drug-metabolizing enzyme, cytochrome P450 2C19 gene in six major ethnicities of Pakistan.

Interindividual differences in cytochrome P450 (CYP) 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for CYP2C19*2 and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for CYP2C19*2 and 8.14% for CYP2C19*3. For CYP2C19*2, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for CYP2C19*3, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19.