Outcomes and efficacy of magnetic resonance imaging-compatible sacral nerve stimulator for management of fecal incontinence: A multi-institutional study

BACKGROUND Fecal incontinence(FI)is an involuntary passage of fecal matter which can have a significant impact on a patient’s quality of life.Many modalities of treatment exist for FI.Sacral nerve stimulation is a well-established treatment for FI.Given the increased need of magnetic resonance imaging(MRI)for diagnostics,the In-terStim which was previously used in sacral nerve stimulation was limited by MRI incompatibility.Medtronic MRI-compatible InterStim was approved by the United States Food and Drug Administration in August 2020 and has been widely used.AIM To evaluate the efficacy,outcomes and complications of the MRI-compatible InterStim.METHODS Data of patients who underwent MRI-compatible Medtronic InterStim placement at UPMC Williamsport,University of Minnesota,Advocate Lutheran General Hospital,and University of Wisconsin-Madison was pooled and analyzed.Patient demographics,clinical features,surgical techniques,complications,and outcomes were analyzed.Strengthening the Reporting of Observational studies in Epidemiology(STROBE)cross-sectional reporting guidelines were used.RESULTS Seventy-three patients had the InterStim implanted.The mean age was 63.29±12.2 years.Fifty-seven(78.1%)patients were females and forty-two(57.5%)patients had diabetes.In addition to incontinence,overlapping symptoms included diarrhea(23.3%),fecal urgency(58.9%),and urinary incontinence(28.8%).Fifteen(20.5%)patients underwent Peripheral Nerve Evaluation before proceeding to definite implant placement.Thirty-two(43.8%)patients underwent rechargeable InterStim placement.Three(4.1%)patients needed removal of the implant.Migration of the external lead connection was observed in 7(9.6%)patients after the stage I procedure.The explanation for one patient was due to infection.Seven(9.6%)patients had other complications like nerve pain,hematoma,infection,lead fracture,and bleeding.The mean follow-up was 6.62±3.5 mo.Sixty-eight(93.2%)patients reported significant improvement of symptoms on follow-up evaluation.CONCLUSION This study shows promising results with significant symptom improvement,good efficacy and good patient outcomes with low complication rates while using MRI compatible InterStim for FI.Further long-term follow-up and future studies with a larger patient population is recommended.

Surgical and non-surgical education practices in female pelvic medicine and reconstructive surgery fellowships within the United States

Data are scarce regarding surgical and non-surgical education in accredited Female Pelvic Medicine and Reconstructive Surgery (FPMRS) fellowships in theUnited States. We compared surgical and non-surgical and education among training programs and expected surgical comfort level with pelvic reconstructive procedures from the perspective of the fellow and program director. An online survey was distributed to program directors and fellows from the 39 accredited FPMRS fellowships at the time (2010). Domains evaluated in the survey were academic education requirements;surgical approaches to prolapse and to incontinence;other surgical procedures;and research and publication expectations. In total, forty fellows from 21 programs and directors from 27 programs. The most common surgical procedures performed for apical, anterior, and posterior prolapse were uterosacral ligament suspension, native tissue anterior colporrhaphy, and posterior colporrhaphy, respectively. Differences in perceived surgical comfort level were seen for coccygeus suspension, graftreinforced posterior colporrhaphy, rectus fascial sling, urethral bulking agent, cystoscopic ureteral stent placement and bowel repair. A greater proportion of program directors reported that fellows would be comfortable performing these procedures upon graduation than the proportion reported by the fellows themselves. Differences exist in FPMRS training nationwide, however, responding fellows appeared to be trained in multiple approaches to prolapse repair. Differences were seen in surgical comfort level as perceived by fellows and program directors.

Evaluation of Methods for Dissemination of Prostate Cancer Survivorship Guidelines: A Survey of Primary Care Providers

Objectives: To assess potential knowledge gaps between primary care providers (PCPs) and cancer specialists, Michigan Cancer Consortium guidelines were developed and disseminated statewide. We evaluated the impact of dissemination of these guidelines on PCP attitudes and beliefs regarding management of prostate cancer (PC) post-treatment sequelae. Methods: Guidelines were disseminated via hard-copy and web-link mailed to 12,000 Michigan PCPs in 2009, and via 5 CME presentations to 181 PCPs in 2010-2011. 132 initial surveys were collected from CME attendees and 549 follow-up surveys were received 20 months after the initial mailing. Results: Surveyed PCPs indicated erectile dysfunction (88%), incontinence (84%), anxiety (54%) and fear of the unknown (50%) as frequent post-treatment sequelae. A minority of PCPs (≤41%) felt “very comfortable” assessing PC patients for ten post-treatment sequelae at the initial survey, which increased by up to 27% on follow-up survey. 93% of PCPs that received guidelines by mail and CME presentation had incorporated them into practice, compared with 72% of PCPs that received guidelines solely by mailing. Similarly, a greater proportion reported practice pattern changes (65% vs. 34%, p = 0.0003). A higher proportion felt CME events (69% vs. 57%) and expert presentations (64% vs. 44%) were “very effective”, when comparing attendees and non-attendees. Conclusions: Guideline distribution resulted in increased comfort with survivorship issues and incorporation into the practices of the majority of PCPs surveyed. A greater impact was observed in PCPs that attended a CME presentation than in those that received guidelines only by mailing.

Increasing thirty-day readmissions of Crohn’s disease and ulcerative colitis in the United States:A national dilemma

BACKGROUND The prevalence of Crohn’s disease(CD)and ulcerative colitis(UC)is on the rise worldwide.This rising prevalence is concerning as patients with CD and UC may frequently relapse leading to recurrent hospitalizations and increased healthcare utilization.AIM To identify trends and adverse outcomes for 30 d readmissions for CD and UC.METHODS This was a retrospective,interrupted trends study involving all adult(≥18 years)30 d readmissions of CD and UC from the National Readmission Database(NRD)between 2008 and 2018.Patients<18 years,elective,and traumatic hospitalizations were excluded from this study.We identified hospitalization characteristics and readmission rates for each calendar year.Trends of inpatient mortality,mean length of hospital stay(LOS)and mean total hospital cost(THC)were calculated using a multivariate logistic trend analysis adjusting for age,gender,insurance status,comorbidity burden and hospital factors.Furthermore,trends between CD and UC readmissions were compared using regression of the interaction coefficient after adjusting for age and gender to determine relative trends between the two populations.Stata®Version 16 software(StataCorp,TX,United States)was used for statistical analysis and P value≤0.05 were considered statistically significant.RESULTS Total number of 30 d readmissions increased from 6202 in 2010 to 7672 in 2018 for CD and from 3272 in 2010 to 4234 in 2018 for UC.We noted increasing trends for 30-day all-cause readmission rate of CD from 14.9%in 2010 to 17.6%in 2018(P-trend<0.001),CD specific readmission rate from 7.1%in 2010 to 8.2%in 2018(P-trend<0.001),30-day all-cause readmission rate of UC from 14.1%in 2010 to 15.7%in 2018(P-trend=0.003),and UC specific readmission rate from 5.2%in 2010 to 5.6%in 2018(P-trend=0.029).There was no change in the risk adjusted trends of inpatient mortality and mean LOS for CD and UC readmissions.However,we found an increasing trend of mean THC for UC readmissions.After comparison,there was no statistical difference in the trends for 30 d all-cause readmission rate,inpatient mortality,and mean LOS between CD and UC readmissions.CONCLUSION There was an increase in total number of 30 d readmissions for CD and UC with a trend towards increasing 30 d all-cause readmission rates.

Multiligament knee injuries with associated tibial plateau fractures: A report of two cases

The management of a combination of fracture and multiligament knee injury(MKI) in traumatic knee injury remains controversial, and there are evolving treatment recommendations. Currently, there are no studies focusing on older adult patients with MKI's in combination with tibia fractures. As a result, there is no well-established treatment algorithm for older adult patients with these complex injuries. We report two cases of MKI's with concomitant fractures in patients fifty years of age or older. Both patients were treated surgically for their associated tibial plateau fractures, but were managed with conservative treatment of the multiligamentous knee injuries. We also provide a review of the literature and guidelines for older adult patients with these types of complex traumatic injuries. Early to mid term acceptable outcomes were achieved for both patients through surgical fixation of the tibial plateau fracture and conservative treatment of the ligament injuries. We propose a comprehensive treatment algorithm for management of these complex injuries.

Truth lies below: A case report and literature review of typical appearing polyps yet with an atypical diagnosis

BACKGROUND Enteropathy associated T-cell lymphoma(EATL) is a rare form of peripheral Tcell lymphoma and makes up less than 5% of gastrointestinal lymphomas. EATL can be divided into type 1 which is associated with celiac disease, and monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL), formally type 2, which is not associated with celiac disease.CASE SUMMARY We present a 60-year-old African American female, without celiac disease, who presented with abdominal pain, diarrhea, and 30 lb. weight loss over a 3 month period. She was subsequently diagnosed with EATL throughout her entire gastrointestinal tract. She is currently undergoing chemotherapy with EOCH(Etoposide, Oncovin, Cyclophosphamide, and Hydroxydaunorubicin). EATL is most common in the Asian and Hispanic population yet the incidence in African Americans is uncertain and emphasizes the rarity of this case. A literature review was included to further emphasize similarities and differences between our case and previously reported cases of MEITL.CONCLUSION The patient was diagnosed with EATL, immunochemical testing was not conclusive for MEITL however was suggestive of the disease.

Causes of Fasting-Evoked en Route Hypoglycemia in Diabetes (FEEHD): A Case Series Study

Background: A recent study reported that some patients with diabetes who fast overnight for laboratory tests are at risk of developing hypoglycemia, which could occur while patients are in risky situations which could result in harm to patients or others. Due to limitation in study design of the aforementioned study, the causes of hypoglycemia could not be elucidated. Objective: To better understand fasting-evoked en route hypoglycemia in diabetes (FEEHD), a recently recognized overlooked safety problem in diabetes management. Methods and Patients: A recent study reported that some patients with diabetes who fast overnight for laboratory tests are at risk of developing hypoglycemia, which could occur while patients are in risky situations which could result in harm to patients or others. Due to limitation in study design of the aforementioned study, the causes of hypoglycemia could not be elucidated. We undertook this retrospective case series study, which enrolled 4 consecutive cases of fasting hypoglycemia in patients with diabetes who were on diverse antidiabetic medications. The study duration was June 1, 2010 to June 1, 2012. Results: The 4 cases (3 women, 1 man), with either type 1 or type 2 diabetes, revealed multiple defects in either the patients’ knowledge and education regarding preparation for lab tests requiring fasting. The degree of hypoglycemia ranged from mild (65 mg/dl) to severe (31 mg/dl), and the events were either mildly symptomatic or asymptomatic. The possible causes of, and contributing factors to hypoglycemia are discussed, and recommendations for preventive measures are provided. Conclusion: Some patients with diabetes who fast for lab tests are at risk of hypoglycemia, and there seems to be an overall lack of proper education of patients with diabetes about this form of hypoglycemia. This overlooked problem can be prevented by proper education and preparation.

Transcriptome changes in stages of non-alcoholic fatty liver disease

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the United States and globally.The currently understood model of pathogenesis consists of a‘multiple hit’hypothesis in which environmental and genetic factors contribute to hepatic inflammation and injury.AIM To examine the genetic expression of NAFLD and non-alcoholic steatohepatitis(NASH)tissue samples to identify common pathways that contribute to NAFLD and NASH pathogenesis.METHODS We employed the Search Tag Analyze Resource for Gene Expression Omnibus platform to search the The National Center for Biotechnology Information Gene Expression Omnibus to elucidate NAFLD and NASH pathology.For NAFLD,we conducted meta-analysis of data from 58 NAFLD liver biopsies and 60 healthy liver biopsies;for NASH,we analyzed 187 NASH liver biopsies and 154 healthy liver biopsies.RESULTS Our results from the NAFLD analysis reinforce the role of altered metabolism,inflammation,and cell survival in pathogenesis and support recently described contributors to disease activity,such as altered androgen and long non-coding RNA activity.The top upstream regulator was found to be sterol regulatory element binding transcription factor 1(SREBF1),a transcription factor involved in lipid homeostasis.Downstream of SREBF1,we observed upregulation in CXCL10,HMGCR,HMGCS1,fatty acid binding protein 5,paternally expressed imprinted gene 10,and downregulation of sex hormone-binding globulin and insulin-like growth factor 1.These molecular changes reflect low-grade inflammation secondary to accumulation of fatty acids in the liver.Our results from the NASH analysis emphasized the role of cholesterol in pathogenesis.Top canonical pathways,disease networks,and disease functions were related to cholesterol synthesis,lipid metabolism,adipogenesis,and metabolic disease.Top upstream regulators included proinflammatory cytokines tumor necrosis factor and IL1B,PDGF BB,and beta-estradiol.Inhibition of beta-estradiol was shown to be related to derangement of several cellular downstream processes including metabolism,extracellular matrix deposition,and tumor suppression.Lastly,we found riciribine(an AKT inhibitor)and ZSTK-474(a PI3K inhibitor)as potential drugs that targeted the differential gene expression in our dataset.CONCLUSION In this study we describe several molecular processes that may correlate with NAFLD disease and progression.We also identified ricirbine and ZSTK-474 as potential therapy.

Dissecting novel mechanisms of hepatitis B virus related hepatocellular carcinoma using meta-analysis of public data

BACKGROUND Hepatitis B virus(HBV) is a cause of hepatocellular carcinoma(HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways were affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation and has implications in early diagnosis and treatment.AIM To elucidate HBV oncogenesis in HCC and identify potential therapeutic targets.METHODS We employed our Search, Tag, Analyze, Resource platform to conduct a meta-analysis of public data from National Center for Biotechnology Information’s Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent nontumor samples and analyzed results with ingenuity pathway analysis.RESULTS Our analysis revealed liver X receptors/retinoid X receptor(RXR) activation and farnesoid X receptor/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene rab-like protein 6(RABL6). The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. We conducted survival analysis that demonstrated increased mortality with higher RABL6 expression. Additionally, homeobox A10(HOXA10) was a top upstream regulator and was strongly upregulated in our analysis. HOXA10 has recently been demonstrated to contribute to HCC pathogenesis in vitro. Our causal analysis suggests an in vivo role through downregulation of tumor suppressors and other mechanisms.CONCLUSION This meta-analysis describes possible roles of RABL6 and HOXA10 in the pathogenesis of HBV-related HCC. RABL6 and HOXA10 represent potential therapeutic targets and warrant further investigation.

Nef-M1, a CXCR4 Peptide Antagonist, Enhances Apoptosis and Inhibits Primary Tumor Growth and Metastasis in Breast Cancer

Results from studies with animal models suggest that, in many cancers, CXCR4 is an important therapeutic target and that CXCR4 antagonists may be promising treatments for primary cancers and for metastases. The Nef protein effectively competes with CXCR4’s natural ligand, SDF-1α, and induces apoptosis. As described in this report, the Nef-M1 peptide (Nef protein amino acids 50 - 60) inhibits primary tumor growth and metastasis of breast cancer (BC). Four BC cell lines (MDA-MB-231, MDA-MB-468, MCF 7, and DU4475) and primary human mammary epithelium (HME) cells were evaluated for their response to the Nef protein and to the Nef-M1 peptide. The presence of CXCR4 receptors in these cells was determined by RT-PCR, Western blot (WB), and immunohistochemical analyses. The apoptotic effect of Nef-M1 was assessed by terminal transferase dUTP nick-end labeling (TUNEL). WBs was used to assess caspase 3 activation. BC xenografts grown in SCID mice were evaluated for the presence of CXCR4 and for their metastatic potential. CXCR4 was presented in MDA-MB-231, MCF 7, and DU 4475 BC cells but not in MDA-MB-468 BC or HME cells. Cells expressing CXCR4 and treated with Nef-M1 peptide or the Nef protein had higher rates of apoptosis than untreated cells. Caspase-3 activation increased in MDA-MB 231 cells treated with the Nef protein, the Nef 41 - 60 peptide, or Nef-M1. Nef-M1, administered to mice starting at the time of xenograft implantation, inhibited growth of primary tumors and metastatic spread. Untreated mice developed diffuse intraperitoneal metastases. We conclude that, in BCs, Nef-M1, through interaction with CXCR4, inhibits primary tumor growth and metastasis by causing apoptosis.

A slight glance at peer review

In order to ensure that the highest quality of literature is published, most journals utilize a peer review process for manuscripts submitted. Although the primary purpose for this process is to filter out "bad science", the process is not perfect. While there is a general consensus among researchers and clinicians that something must be done to improve upon the method for properly vetting manuscripts, there are conflicting opinions on how to best implement new policies. In this paper, we discuss the most well-supported suggestions to improve the process, with the hopes of increasing rigor and reproducibility, ensuring double-blinding, developing set guidelines, offering early training to reviewers, and giving reviewers better feedback and recognition for their work.

Laparoendoscopic single site,laparoscopic or open surgery for adrenal tumors:Selecting the optimal approach

Numerous surgical modalities are available to treat adrenal lesions. Minimally-invasive approaches for adrenalectomy are indicated in most circumstances, and new evidence continues to be accumulated. In this context, current indications for open surgical adrenalectomy(OS-A), minimally-invasive adrenalectomy(MI-A), and laparoendoscopic single-site adrenalectomy(LESS-A) remain unclear. A comprehensive Englishlanguage literature review was performed using MEDLINE/Pub MED to identify articles and guidelines pertinent to the surgical management of adrenal tumors. A comprehensive chart review was performed for three illustrative cases. Clinical recommendations were generated based on relevant literature and the expertise of the investigator group. MI-A offers advantages over OS-A in properly selected patients, who experience fewer complications, lower blood loss, and shorter hospital stays. Robot-assisted laparoscopic and retroperitoneoscopic adrenalectomy may offer advantages over transperitoneal surgery, and LESS-A may be an even less-invasive option that will require further evaluation. MI-A remains the surgical treatment of choice for most adrenal lesions. Tumor size and stage are the primary indications for selecting alternative treatment modalities. OS-A remains the gold standard for large tumors(> 10 cm) and suspected or known advanced stage malignancy. LESS-A appears to be an appropriate initial approach for small tumors(< 4-5 cm), including pheochromocytoma and isolated adrenal metastases.

常见的色素沉着病

尽管绝大多数色素沉着疾病都是良性的或是非特异性的，但是当对其病情进行评估和治疗时，有些皮肤色素沉着疾病着实给患者带来了美容修饰的难度和心理上挑战；有些皮肤色素沉着疾病可能提示潜在的系统性疾病或者原发性皮肤恶性肿瘤。要求医师恰当地诊断这些皮肤病变，并给予患者适当的治疗和安慰。

Pregnancy and Metabolic-associated Fatty Liver Disease:A Clinical Update

The intricate relationship between metabolic-associated fatty liver disease(MAFLD)and maternal complications has rapidly become a significant health threat in pregnant women.The presence of MAFLD in pregnancy increases the maternal risk of metabolic complications and comorbidities for both mother and baby.The preexistence or development of MAFLD in pregnancy is a complex multifactorial disorder that can lead to further complications for mother and baby.Therefore,as pregnant women are severely underrepresented in clinical research,there is a great need for a fair inclusion of this group in clinical trials.This review aims to explore the effects of MAFLD during pregnancy in the context of maternal complications and outcomes and explore the effects of pregnancy on the development and progression of MAFLD within the context of maternal obesity,altered metabolic profiles,gestational diabetes and altered hormonal profiles.We also addressed potential implications for the presence of MAFLD during pregnancy and its management in the clinical setting.

The Pregnancy Heart Team Approach for the Adult with Hypertrophic Cardiomyopathy and Severe Left Ventricular Outflow Tract Obstruction

Hypertrophic cardiomyopathy (HCM), the most common single-gene cardiovascular disease, is associated with increased risk for arrhythmias, heart failure, and sudden cardiac death. The hemodynamic changes known to occur during pregnancy can exacerbate heart failure and arrhythmias in women with HCM. We present a 30-year-old woman with HCM to illustrate the benefits of multidisciplinary team management of severe left ventricular outflow tract obstruction (peak gradient >100 mmHg) for optimal maternal and fetal outcomes.