Real-World Surgical and Endoscopic Recurrence Based on Risk Profiles and Prophylaxis Utilization in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort. METHODS: In this multicenter retrospective analysis, patients with CD who underwent ileocolonic resection (ICR) from 2009 to 2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating disease, and/or perianal disease) and low-risk (nonsmokers and age >50 y) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeert score, ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses. RESULTS: A total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, 2 or more ICRs (odds ratio [OR], 1.71; 95% CI, 1.13-2.57), active smoking (OR, 1.73; 95% CI, 1.17-2.53), penetrating disease (OR, 1.41; 95% CI, 1.02-1.94), and history of perianal disease alone (OR, 1.99; 95% CI, 1.42-2.79) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis vs not (10.2% vs 16.7%; P = .02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (high-risk, 28.1% vs 37.4%; P = .03; and low-risk, 21.1% vs 38.3%; P = .002). CONCLUSIONS: Clinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this.

Histologic Activity From Neoterminal Ileal Biopsies in Patients With Crohn's Disease in Endoscopic Remission is Associated With Postoperative Recurrence.

INTRODUCTION: Following ileocolic resection (ICR), the clinical importance and prognostic implications of histologic activity on biopsies in Crohn's disease (CD) patients with endoscopic remission are not well defined. The aim of this study was to determine if histologic activity in patients with endoscopic remission is associated with future risk of endoscopic and/or radiologic postoperative recurrence (POR). METHODS: In this multicenter retrospective cohort study, adult patients with CD who underwent ICR between 2009 and 2020 with endoscopic biopsies of ileal mucosa from Rutgeerts i0 on index colonoscopy were included. The composite rate of endoscopic (Rutgeerts score ≥i2b) and radiologic (active inflammation on imaging) recurrence was compared in patients with and without histologic activity using a Kaplan-Meier survival analysis. A multivariable Cox proportional hazard regression model including clinically relevant risk factors of POR, postoperative biologic prophylaxis, and histology activity was designed. RESULTS: A total of 113 patients with i0 disease on index colonoscopy after ICR were included. Of these, 42% had histologic activity. Time to POR was significantly earlier in the histologically active versus normal group ( P = 0.04). After adjusting for clinical risk factors of POR, histologic activity (HR 2.37, 95% CI 1.17-4.79; P = 0.02) and active smoking (HR 2.54, 95% CI 1.02-6.33; P = 0.05) were independently associated with subsequent composite POR risk. DISCUSSION: In patients with postoperative CD, histologic activity despite complete endoscopic remission is associated with composite, endoscopic, and radiographic recurrence. Further understanding of the role of histologic activity in patients with Rutgeerts i0 disease may provide a novel target to reduce disease recurrence in this population.

Peri-Operative Optimization of Patients with Crohn's Disease.

PURPOSE OF REVIEW: The management of patients with Crohn's disease (CD) undergoing surgery is complex and optimization of modifiable factors perioperatively can improve outcomes. This review focuses on the perioperative management of CD patients undergoing surgery, emphasizing the need for a multi-disciplinary approach. RECENT FINDINGS: Research highlights the benefits of a comprehensive strategy, involving nutritional optimization, psychological assessment, and addressing septic complications before surgery. Despite many CD patients being on immune-suppressing medications, studies indicate that most of these medications are safe to use and should not delay surgery. However, a personalized approach for each case is needed. This review underscores the importance of multi-disciplinary team led peri-operative management of CD patients. We suggest that this can be done at a dedicated perioperative clinic for prehabilitation, with the potential to enhance outcomes for CD patients undergoing surgery.

Anastomotic Configuration and Temporary Diverting Ileostomy Do Not Increase Risk of Anastomotic Stricture in Postoperative Crohn's Disease.

INTRODUCTION: Surgical management of Crohn's disease (CD) is common. Postoperative complications include anastomotic stricturing (AS). The natural history and risk factors for AS have not been elucidated. METHODS: A retrospective cohort study of patients with CD who underwent ileocolonic resection (ICR) with ≥1 postoperative ileocolonoscopy between 2009 and 2020. Postoperative ileocolonoscopies with corresponding cross-sectional imaging were evaluated for evidence of AS without neoterminal ileal extension. Severity of AS and endoscopic intervention at time of detection were collected. Primary outcome was development of AS. Secondary outcome was time to AS detection. RESULTS: A total of 602 adult patients with CD underwent ICR with postoperative ileocolonoscopy. Of these, 426 had primary anastomosis, and 136 had temporary diversion at time of ICR. Anastomotic configuration consisted of 308 side-to-side, 148 end-to-side, and 136 end-to-end. One hundred ten (18.3%) patients developed AS with median time of 3.2 years to AS detection. AS severity at time of detection was associated with need for repeat surgical resection for AS. On multivariable Cox proportional hazard regression, anastomotic configuration and temporary diversion were not associated with risk of or time to AS. Preoperative stricturing disease was associated with decreased time to AS (adjusted hazard ratio 1.8; P = 0.049). Endoscopic ileal recurrence before AS was not associated with subsequent AS detection. DISCUSSION: AS is a relatively common postoperative CD complication. Patients with previous stricturing disease behavior are at increased risk of AS. Anastomotic configuration, temporary diversion, and ileal CD recurrence do not increase risk of AS. Early detection and intervention for AS may help prevent progression to repeat ICR.

Referral, Uptake, and Outcome of Genetic Counseling and Testing in Patients With Early-Onset Colorectal Cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC. METHODS: We conducted a retrospective cohort study of patients aged <50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake. RESULTS: A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51-2.96) and more recent year of diagnosis (2010-2013 vs 2017-2019; OR, 5.36; 95% CI, 3.59-8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86-0.92). CONCLUSIONS: Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.

Change in Biologic Class Promotes Endoscopic Remission Following Endoscopic Postoperative Crohn's Disease Recurrence.

GOALS: Assess the outcomes of various therapeutic regimens to treat initial endoscopic postoperative recurrence despite biologic prophylaxis. BACKGROUND: Postoperative biologic prophylaxis reduces postoperative Crohn's disease (CD) recurrence rates. Optimal treatment strategies for endoscopic recurrence have not been elucidated. STUDY: Retrospective cohort study of adult CD patients who underwent ileocolonic resection between 2009 and 2020. Patients with endoscopic postoperative recurrence despite prophylactic biologic therapy and ≥1 subsequent colonoscopy were included. Treatment changes after recurrence were categorized as (1) therapy optimization or continuation or (2) new biologic class. The primary outcome was composite endoscopic or surgical recurrence at the time of or prior to subsequent follow-up colonoscopy. RESULTS: Eighty-one CD patients with endoscopic recurrence (54.3% i2b, 22.2% i3, and 23.5% i4) despite biologic prophylaxis (86.4% anti-tumor necrosis factor, 8.6% vedolizumab, 4.9% ustekinumab) were included. Most patients received therapy optimization or continuation (76.3%, n=61) following recurrence compared to being started on a new biologic class. Sixty patients (N=48 therapy optimization; N=12 new biologic class) experienced composite recurrence (78.3% endoscopic, 21.7% surgical). On multivariable modeling, initiation of a new biologic class was associated with reduced risk for composite recurrence compared to therapy optimization or continuation (aOR: 0.26; P=0.04). Additionally, initiation of a new biologic class was associated with endoscopic improvement when adjusting for endoscopic severity at the time of recurrence (aOR: 3.4; P=0.05). On sensitivity analysis, a new biologic class was associated or trended with improved rates of endoscopic healing and composite recurrence when directly compared to therapy optimization or continuation. CONCLUSION: In patients with CD who experience endoscopic recurrence despite biologic prophylaxis, changing the mechanism of biologic action may promote endoscopic improvement.

Association of self-reported happiness with sociodemographic factors and personal habits amongst students in a university in Karachi.

The aim of this study was to determine the association of happiness with sociodemographic factors and personal habits among university students in Karachi, Pakistan. This cross-sectional study was conducted at Bahria University (BU), Karachi, from January 2012 till December 2013 on 813 students. There was a significant positive relationship between happiness and having a well-off family background (p value<0.001), having breakfast (p value=0.021), wearing a seat belt (p value=0.005) and getting regular dental check-ups (p value<0.001). We also found a significant negative association between happiness and the use of tobacco (p value=0.048), being on a weight loss diet (p value=0.048) and being married (p value=0.043). Hence, behaviours such as smoking and following unhealthy weight loss diets are proven to be associated negatively with a person's state of happiness and should be discouraged; while healthy behaviours such as having breakfast and getting dental check-ups should be encouraged.

Intracytoplasmic sperm injection and advanced maternal age: Success or treatment failure?

Infertility rate documented in Pakistan is 21.9% with only 25% success rate even after procedures like intracytoplasmic sperm injection (ICSI). This rate is further on the decline with enhancement of female age. We aimed to observe the effect of female age on oocyte parameters and reproductive outcome after ICSI. It was done by retrospective analysis of a quasi- experimental design carried out after approval from "Ethical review board of Islamabad clinic serving infertile couples" from July 2010 to August 2011. The response to ovarian stimulation in (282) females was assessed on the basis of groups, A, B, C and D with age ranges up to 25years; 25.1 to 30years; 30.1 to 35years and >35years, respectively. The outcome was assessed as non-pregnant, preclinical abortion and clinical pregnancy groups on the basis of beta hCG and cardiac activity by trans-vaginal scan. We observed that maximum number of pregnancies 32 (38%) occurred in C group, and least 10 (10%) in group A. There was a statistical reduction in the number of mature and fertilized oocytes as the age advanced from group C to D (p<0.05).This shows that reduction in maturity and fertilization of oocytes with advancement of age recommends early referral of couples to assisted reproductive clinics.

FSH/LH ratio in females and intracytoplasmic sperm injection.

OBJECTIVE: To observe the effect of follicle stimulating hormone-luteinizing hormone ratio on oocyte parameters, quality of embryo, implantation and clinical pregnancy rate after intracytoplasmic sperm injection. METHODS: The retrospective study was conducted at a fertility clinic in Islamabad, Pakistan, and comprised data of primary infertile females who underwent intracytoplasmic sperm injection from June 2011 to March 2013. All subjects had duration of infertility more than two years, and age range was 20-40 years. Follicle stimulating hormone and luteinizing hormone were estimated by enzyme-linked immunosorbent assay on day 3 of the cycle and the ratio was calculated. Groups were stratified on the basis of median ratio into groups I <1.26 and group II >1.26. SPSS 20 was used for data analysis. RESULTS: Of the 282 females, 143(51%) were in group I and 139(49%) in group II. Pregnancy was acquired by 79(55%) and 22(16%) females in group I and II respectively. The number of retrieved, metaphase, fertilised oocytes, cleaved embryos and endometrial thickness was significantly larger in group I (p< 0.0001). CONCLUSIONS: Follicle stimulating hormone-luteinizing hormone ratio less than 1.26 was associated with good oocyte parameters, top quality embryo and implantation after intracytoplasmic sperm injection.

A systematic review of preoperative transjugular intrahepatic portosystemic shunt prior to extrahepatic, abdominal surgery in patients with cirrhosis.

BACKGROUND: Extrahepatic, abdominal surgery in patients with cirrhosis is associated with high morbidity and mortality. This systematic review presents the current evidence available on the utility of a preoperative transjugular intrahepatic portosystemic shunt (TIPS), assessed by its effect on surgical candidacy and postoperative mortality and morbidity in patients with cirrhosis undergoing extrahepatic, abdominal surgery. METHODS: MEDLINE, EMBASE, Cochrane Library and Web of Science databases were searched till 2022 to identify studies. Studies that reported characteristics and outcomes of participants with cirrhosis that had a TIPS inserted in preparation for extrahepatic, abdominal surgery, were included. RESULTS: Twenty-one studies (292 patients) were included, of which three were comparative studies and the remaining case series or case reports. A TIPS was inserted in 190 patients prior to surgery. At least one clinical sign of portal hypertension identified by ascites, varices, and/or hepatic encephalopathy were present in all patients except one patient. Fifty eight percent had decompensated cirrhosis. TIPS insertion was successful in all patients. Eighty-nine percent of patients underwent surgery. The cumulative 30-day postoperative mortality was 2% (3/148). There were 97 complications reported in 168 patients (57%). In the three comparative studies, there was no difference in mortality or morbidity among patients who underwent TIPS prior to surgery compared to those who did not undergo TIPS prior to surgery. CONCLUSION: Preoperative TIPS has been used to improve surgical candidacy in patients with cirrhosis undergoing extrahepatic, abdominal surgery, while reducing complications of portal hypertension. However, there is not enough evidence to support that TIPS insertion prior to extrahepatic, abdominal surgery significantly improves surgical outcomes in patients with cirrhosis and further studies are needed.

Molecular Adsorbent Recirculating System in Acute Liver Failure.

Acetaminophen (APAP) overdose is the most common cause of acute liver failure (ALF) in the United States. Liver transplantation (LT) is potentially lifesaving for patients with ALF, but its feasibility in clinical practice is limited. Liver assist devices, such as the Molecular Adsorbent Recirculating System (MARS), are used in some centers as a "bridge" to liver transplantation or as a means of liver recovery, but their role in the treatment of ALF is not well-defined. We present the case of a 44-year-old man with APAP-associated ALF who experienced hepatic recovery after treatment with MARS.

Postoperative Crohn's Disease Recurrence Risk and Optimal Biologic Timing After Temporary Diversion Following Ileocolic Resection.

BACKGROUND: Postoperative recurrence of Crohn's disease (CD) is common. While most patients undergo resection with undiverted anastomosis (UA), some individuals also have creation of an intended temporary diversion (ITD) with an ileostomy followed by ostomy takedown (OT) due to increased risk of anastomotic complications. We assessed the association of diversion with subsequent CD recurrence risk and the influence of biologic prophylaxis timing to prevent recurrence in this population. METHODS: This was a retrospective cohort study of CD patients who underwent ileocolic resection between 2009 and 2020 at a large quaternary health system. Patients were grouped by continuity status after index resection (primary anastomosis or ITD). The outcomes of the study were radiographic, endoscopic, and surgical recurrence as well as composite recurrence postoperatively (after OT in the ITD group). Propensity score-weighted matching was performed based on risk factors for diversion and recurrence. Multivariable regression and a Cox proportional hazards model adjusting for recurrence risk factors were used to assess association with outcomes. Subgroup analysis in the ITD group was performed to assess the impact of biologic timing relative to OT (no biologic, biologic before OT, after OT) on composite recurrence. RESULTS: A total of 793 CD patients were included (mean age 38 years, body mass index 23.7 kg/m2, 52% female, 23% active smoker, 50% penetrating disease). Primary anastomosis was performed in 67.5% (n = 535) and ITD in 32.5% (n = 258; 79% loop, 21% end) of patients. Diverted patients were more likely to have been males and to have had penetrating and perianal disease, prior biologic use, lower body mass index, and lower preoperative hemoglobin and albumin (all P < .01). After a median follow-up of 44 months, postoperative recurrence was identified in 83.3% patients (radiographic 40.4%, endoscopic 39.5%, surgical 13.3%). After propensity score matching and adjusting for recurrence risk factors, no significant differences were seen between continuity groups in radiographic (adjusted hazard ratio [aHR], 1.32; 95% confidence interval [CI], 0.91-1.91) or endoscopic recurrence (aHR, 1.196; 95% CI, 0.84-1.73), but an increased risk of surgical recurrence was noted in the ITD group (aHR, 1.61; 95% CI, 1.02-2.54). Most (56.1%) ITD patients started biologic prophylaxis after OT, 11.4% before OT, and 32.4% had no postoperative biologic prophylaxis. Biologic prophylaxis in ITD was associated with younger age (P < .001), perianal disease (P = .04), and prior biologic use (P < .001) but not in recurrence (P = .12). Despite higher rates of objective disease activity identified before OT, biologic exposure before OT was not associated with a significant reduction in composite post-OT recurrence compared with starting a biologic after OT (52% vs 70.7%; P = 0.09). CONCLUSIONS: Diversion of an ileocolic resection is not consistently associated with a risk of postoperative recurrence and should be performed when clinically appropriate. Patients requiring diversion at time of ileocolic resection are at high risk for recurrence, and biologic initiation prior to stoma reversal may be considered.

Diversion of an ileocolic resection is not consistently associated with a risk of postoperative recurrence and should be performed when clinically appropriate. Patients requiring diversion at time of ileocolic resection are high risk for recurrence, and biologic initiation prior to stoma reversal may be considered.

Interplay between oxidative stress, SIRT1, reproductive and metabolic functions.

Silent information Regulators (SIRT1) gene stimulates antioxidants' expression, repairs cells damaged by oxidative stress (OS), and prevents the cells' dysfunction. In particular, the role of different Sirtuins, particularly SIRT1 in reproduction, has been widely studied over the past decade. Decreased SIRT 1 causes mitochondrial dysfunction by increasing Reactive Oxygen Species (ROS), lipid peroxidation, and DNA damage in both male and female gametes (Sperms and Oocytes), leading to infertility. In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), and its down-regulation is associated with a reduced ovarian reserve. SIRT1 also modulates the stress response to OS in GCs by targeting a transcription factor vital for ovarian functions and maintenance. ROS-mediated damage to spermatozoa's motility and morphology is responsible for 30-80% of men's infertility cases. High levels of ROS can cause damage to deoxyribo nucleic acid (DNA) in the nucleus and mitochondria, lipid peroxidation, apoptosis, inactivation of enzymes, and oxidation of proteins in spermatozoa. SIRT 1 is a cardioprotective molecule that prevents atherosclerosis by modulating various mechanisms such as endothelial injury due to impaired nitric oxide (NO) production, inflammation, OS, and regulation of autophagy. SIRT 1 is abundantly expressed in tubular cells and podocytes. It is also found to be highly expressed in aquaporin 2 positive cells in the distal nephron suggesting its involvement in sodium and water handling. SIRT1 improves insulin resistance by reducing OS and regulating mitochondrial biogenesis and function. It also decreases adiposity and lipogenesis and increases fatty acid oxidation. So, its involvement in the multiple pathways ensures its unique role in reproductive and metabolic derangement mechanisms.

Role of Cardiologists in the Management of Systemic Lupus Erythematosus: First Reported Case of Three-vessel Disease in a Young Woman in Pakistan.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder with predilection towards young women. SLE is associated with increased risk of incidence of cardiac diseases which include atherosclerosis and coronary artery disease (CAD) that can present clinically as angina or myocardial infarction (MI) or be clinically silent in the initial stages. Furthermore, the use of corticosteroids for the treatment of SLE exacerbates the risk of thrombosis, possibly resulting in adverse cardiovascular events in such patients. Antiphospholipid syndrome (APS) is another autoimmune condition which can occur in the setting of SLE, also resulting in hypercoagulability and thrombosis. This goes on to show how important a role cardiologists play in anticipating and managing the cardiac manifestations of SLE, which can significantly reduce the morbidity and mortality of SLE patients. Here we present a case of a young woman with SLE having three-vessel disease, presenting in the cardiac emergency department of Civil Hospital, Karachi with typical chest pain. This case is the first of its kind to be reported in Pakistan, to the best of our knowledge.

Relationship of Serum Leptin and Reproductive Hormones in Unexplained Infertile and Fertile Females.

OBJECTIVE: To investigate the relationship between serum leptin and reproductive hormones in females with unexplained infertility (UI). METHODOLOGY: It was a case-control study conducted in the Gynecology and Obstetrics Department and Infertility Clinic, Jinnah Postgraduate Medical Center (JPMC), Karachi, Pakistan. A total of 235 primary infertile females with an unidentified cause of infertility were selected from the Infertility Clinics. The patients were excluded if they were found to have polycystic ovary syndrome, endometriosis, tubal blockage, irregular menstrual cycles, hyperthyroidism, hypothyroidism, hyperprolactinemia, hyperandrogenemia, fasting blood sugar >110 mg/dl, and male factor infertility. A total of 205 healthy, fertile females were selected from the general population. The blood samples of both groups were collected on the 12th and 21st day of their menstrual cycle. Serum leptin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and E2 levels were measured. Statistical analysis was executed using the SPSS version 16 (SPSS Inc., Chicago, IL). RESULTS: No significant difference was observed in leptin values of fertile and UI females, 37.110±1.19 vs. 35.321±0.901. In the preovulatory phase (12th day) of the cycle, infertile subjects with body mass index (BMI) <20 and 20-24.9 had significantly higher values for leptin (p<0.05), whereas, with an increase in BMI, leptin levels were reduced in these females. Leptin was reduced further in the luteal phase of infertile females with BMI 25-30, with a significantly lower value for FSH (p<0.005), LH (p<0.005), and estradiol (p<0.005. In infertile subjects, it correlated with estradiol (r=0.501, p<0.005), BMI (r=0.903, p<0.001), and progesterone (r=0.146, p<0.05). CONCLUSION: Low levels of leptin observed to have an increase in the BMI of UI females were associated with a reduced estradiol and progesterone production in the luteal phase of the cycle.