Transobturator mid urethral sling surgery for stress urinary incontinence: our experience

Background: We retrospectively evaluated the cure & improvement rate and complications incidence following transobturator approach of mid urethral sling surgery (MUS) for stress urinary incontinence (SUI).Methods: Of the total 52 patients who underwent transobturator approach of midurethral sling surgery for stress urinary incontinence at Dr. Ramesh Hospital, Bangalore, India, between January 2006 – December 2009, 48 women were available for clinical follow-up investigation. At follow-up, all 48 patients underwent a cough test, a pad test, and sonographic postvoid residual volume measurement. Women rated their subjective continence status (continent, slightly incontinent, incontinent). Objective cure was defined as a pad weight 0–1 g and a negative cough test.Results: The minimum and median follow-up was 12 months & 24 months respectively. Subjectively, 93.75 % of the patients rated themselves as continent, 2.08% as slightly incontinent, and 4.16 % as severely incontinent. The objective cure rate was 93.75%. The surgery failed in 3 patients (6.25%). 2 patients (4.16%) underwent repeat surgery. There was one case (2.08%) of vaginal erosion of mesh which required excision of the exposed part and one case (2.08%) of urinary retention requiring incision of the mesh at the center.Conclusions: Transobturator approach of mid urethral sling surgery is a safe, effective and minimally invasive procedure for SUI with a very low rate of complications

Single incision laparoscopic cystectomy for a huge fimbrial cyst: a rare case report

A case of huge fimbrial cyst is presented, occurring in a 26 year old female. She presented in outpatient department with an incidental diagnosis of a huge cystic mass diagnosed during her routine medical check-up. She was asymptomatic. Ultrasound and CT scan showed an abdominopelvic cystic mass in left adnexa and a right dermoid cyst. Single incision laparoscopic surgery was performed and a huge right fimbrial cyst of 35 cm was noted along with left dermoid cyst. We did bilateral cystectomy through single port laparoscopy.  Although there are a few case reports on huge fimbrial cysts which were managed traditionally by laparotomy and recently multiport laparoscopic surgeries, the technique of single incision laparoscopic surgery for proved benign cysts has been described here

Long-Term (10-Year) Gastrointestinal and Genitourinary Toxicity after Treatment with External Beam Radiotherapy, Radical Prostatectomy, or Brachytherapy for Prostate Cancer

Objective.To examine gastrointestinal (GI) and genitourinary (GU) toxicity profiles of patients treated in 1999 with external beam radiotherapy (RT), prostate interstitial brachytherapy (PI) or radical prostatectomy (RP). Methods. TThe records of 525 patients treated in 1999 were reviewed to evaluate toxicity. Late GI and GU morbidities were graded according to the RTOG late morbidity criteria. Other factors examined were patient age, BMI, smoking history, and medical co-morbidities. Due to the low event rate for late GU and GI toxicities, a competing risk regression (CRR) analysis was done with death as the competing event. Results. Median follow-up time was 8.5 years. On CRR univariate analysis, only the presence of DM was significantly associated with GU toxicity grade >2 (P = 0.43, HR 2.35, 95% Cl = 1.03–5.39). On univariate analysis, RT and DM were significantly associated with late GI toxicity. On multivariable analysis, both variables remained significant (RT: P = 0.038, HR = 4.71, CI = 1.09–20.3; DM: P = 0.008, HR = 3.81, 95% Cl = 1.42–10.2). Conclusions. Late effects occur with all treatment modalities. The presence of DM at the time of treatment was significantly associated with worse late GI and GU toxicity. RT was significantly associated with worse late GI toxicity compared to PI and RP

Association of Disease Recurrence With Survival Outcomes in Patients With Cutaneous Squamous Cell Carcinoma of the Head and Neck Treated With Multimodality Therapy

IMPORTANCE It has previously been demonstrated that immunosuppressed patients with cutaneous squamous cell cancer of the head and neck (cSCC-HN) treated with surgery and postoperative radiotherapy have significantly inferior disease-related outcomes compared with immunocompetent patients, but data on outcomes after disease recurrence are limited. OBJECTIVES To report survival outcomes in patients with cSCC-HN after disease recurrence after surgery and postoperative radiotherapy and to investigate the association of immune status with disease-related outcomes. DESIGN, SETTING, AND PARTICIPANTS A multi-institutional study of 205 patients treated at the Cleveland Clinic, Washington University in St Louis, and the University of California, San Francisco, in which patients who underwent surgical resection and postoperative radiotherapy for primary or recurrent stage I to IV (nonmetastatic) cSCC-HN between January 1, 1995, and December 31, 2014, were identified. Patients with any disease recurrence, defined as local, regional, and/or distant failure, were included. Patients were categorized as immunosuppressed if they received a diagnosis of chronic hematologic malignant neoplasm or HIV or AIDS, or were treated with immunosuppressive therapy for organ transplantation 6 months or more before diagnosis. Statistical analysis was conducted from January 1, 1995, to December 31, 2015. MAIN OUTCOMES AND MEASURES Overall survival calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS Of the 205 patients in the original cohort, 72 patients (63 men and 9 women; median age, 71 years [range, 43-91 years]) developed disease recurrence after surgery and postoperative radiotherapy. Forty patients (55.6%) were immunosuppressed, and 32 patients (44.4%) were immunocompetent. Locoregional recurrence was the most common first pattern of failure for both groups (31 immunosuppressed patients [77.5%]; 21 immunocompetent patients [65.6%]). After any recurrence, 1-year overall survival was 43.2%(95% CI, 30.9%-55.4%), and median survival was 8.4 months. For patients for whom information on salvage treatment was available (n = 45), those not amenable to surgical salvage had significantly poorer median cumulative incidence of survival compared with those who were amenable to surgical salvage (4.7 months; 95% CI, 3.7-7.0 months vs 26.1 months; 95% CI, 6.6 months to not reached; P=.01), regardless of their immune status. CONCLUSIONS AND RELEVANCE Results of this study suggest that patients with cSCC-HN who experience disease recurrence after definitive treatment with surgery and postoperative radiotherapy have poor survival, irrespective of immune status. Survival rates are low for patients with recurrent disease that is not amenable to surgical salvage. The low rate of successful salvage underscores the importance of intensifying upfront treatment to prevent recurrence.12 month embargo; published online: 27 February 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Leveraging Genomic Associations in Precision Digital Care for Weight Loss: Cohort Study

Background: The COVID-19 pandemic has highlighted the urgency of addressing an epidemic of obesity and associated inflammatory illnesses. Previous studies have demonstrated that interactions between single-nucleotide polymorphisms (SNPs) and lifestyle interventions such as food and exercise may vary metabolic outcomes, contributing to obesity. However, there is a paucity of research relating outcomes from digital therapeutics to the inclusion of genetic data in care interventions. Objective: This study aims to describe and model the weight loss of participants enrolled in a precision digital weight loss program informed by the machine learning analysis of their data, including genomic data. It was hypothesized that weight loss models would exhibit a better fit when incorporating genomic data versus demographic and engagement variables alone. Methods: A cohort of 393 participants enrolled in Digbi Health’s personalized digital care program for 120 days was analyzed retrospectively. The care protocol used participant data to inform precision coaching by mobile app and personal coach. Linear regression models were fit of weight loss (pounds lost and percentage lost) as a function of demographic and behavioral engagement variables. Genomic-enhanced models were built by adding 197 SNPs from participant genomic data as predictors and refitted using Lasso regression on SNPs for variable selection. Success or failure logistic regression models were also fit with and without genomic data. Results: Overall, 72.0% (n=283) of the 393 participants in this cohort lost weight, whereas 17.3% (n=68) maintained stable weight. A total of 142 participants lost 5% bodyweight within 120 days. Models described the impact of demographic and clinical factors, behavioral engagement, and genomic risk on weight loss. Incorporating genomic predictors improved the mean squared error of weight loss models (pounds lost and percent) from 70 to 60 and 16 to 13, respectively. The logistic model improved the pseudo R 2 value from 0.193 to 0.285. Gender, engagement, and specific SNPs were significantly associated with weight loss. SNPs within genes involved in metabolic pathways processing food and regulating fat storage were associated with weight loss in this cohort: rs17300539_G (insulin resistance and monounsaturated fat metabolism), rs2016520_C (BMI, waist circumference, and cholesterol metabolism), and rs4074995_A (calcium-potassium transport and serum calcium levels). The models described greater average weight loss for participants with more risk alleles. Notably, coaching for dietary modification was personalized to these genetic risks. Conclusions: Including genomic information when modeling outcomes of a digital precision weight loss program greatly enhanced the model accuracy. Interpretable weight loss models indicated the efficacy of coaching informed by participants’ genomic risk, accompanied by active engagement of participants in their own success. Although large-scale validation is needed, our study preliminarily supports precision dietary interventions for weight loss using genetic risk, with digitally delivered recommendations alongside health coaching to improve intervention efficac

Phylogeography of mtDNA haplogroup R7 in the Indian peninsula.

BACKGROUND: Human genetic diversity observed in Indian subcontinent is second only to that of Africa. This implies an early settlement and demographic growth soon after the first 'Out-of-Africa' dispersal of anatomically modern humans in Late Pleistocene. In contrast to this perspective, linguistic diversity in India has been thought to derive from more recent population movements and episodes of contact. With the exception of Dravidian, which origin and relatedness to other language phyla is obscure, all the language families in India can be linked to language families spoken in different regions of Eurasia. Mitochondrial DNA and Y chromosome evidence has supported largely local evolution of the genetic lineages of the majority of Dravidian and Indo-European speaking populations, but there is no consensus yet on the question of whether the Munda (Austro-Asiatic) speaking populations originated in India or derive from a relatively recent migration from further East. RESULTS: Here, we report the analysis of 35 novel complete mtDNA sequences from India which refine the structure of Indian-specific varieties of haplogroup R. Detailed analysis of haplogroup R7, coupled with a survey of approximately 12,000 mtDNAs from caste and tribal groups over the entire Indian subcontinent, reveals that one of its more recently derived branches (R7a1), is particularly frequent among Munda-speaking tribal groups. This branch is nested within diverse R7 lineages found among Dravidian and Indo-European speakers of India. We have inferred from this that a subset of Munda-speaking groups have acquired R7 relatively recently. Furthermore, we find that the distribution of R7a1 within the Munda-speakers is largely restricted to one of the sub-branches (Kherwari) of northern Munda languages. This evidence does not support the hypothesis that the Austro-Asiatic speakers are the primary source of the R7 variation. Statistical analyses suggest a significant correlation between genetic variation and geography, rather than between genes and languages. CONCLUSION: Our high-resolution phylogeographic study, involving diverse linguistic groups in India, suggests that the high frequency of mtDNA haplogroup R7 among Munda speaking populations of India can be explained best by gene flow from linguistically different populations of Indian subcontinent. The conclusion is based on the observation that among Indo-Europeans, and particularly in Dravidians, the haplogroup is, despite its lower frequency, phylogenetically more divergent, while among the Munda speakers only one sub-clade of R7, i.e. R7a1, can be observed. It is noteworthy that though R7 is autochthonous to India, and arises from the root of hg R, its distribution and phylogeography in India is not uniform. This suggests the more ancient establishment of an autochthonous matrilineal genetic structure, and that isolation in the Pleistocene, lineage loss through drift, and endogamy of prehistoric and historic groups have greatly inhibited genetic homogenization and geographical uniformity.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Microalbuminuria and Target Organ Damage in Nondiabetic Hypertensive Patients

Introduction: Hypertension is the most important non communicable disease with unprecendented increase in prevalence all over the globe including in our country. Microalbuminuria, or aberrant urine albumin excretion ranging from 30 to 300 mg/day, affects between 5% to 40% of people with essential hypertension. It has been discovered that in 5% to 40% of people with essential hypertension.Aims: The purpose of this study was to assess the prevalence of microalbuminuria in nondiabetic hypertensive people and to look into the relationship between microalbuminuria and the patient's age, HTN duration, blood pressure level, and other coronary risk factors.Materials and Methodology: This prospective cross-sectional study was done in the department of General Medicine at ASRAM Medical College among patients hospitalized to the medical wards and those attending the medical outpatient unit who were diagnosed with hypertension from October 2020 to September 2021.Results: Among patients with microalbuminuria,abnormal lipid profile was present in 73.2% patients. The association between the groups was discovered to be statistically significant. Patients with microalbuminuria, 70.7% belong to stage 1 hypertension and 29.3% belong to stage 2 hypertension which was found to be statistically significant.Grade 1 hypertensive retinopathy was present in 19.5% patients, grade 2 hypertensive retinopathy was present in 7.3% patients, grade 3 hypertensive retinopathy was present in 19.5% patients and grade 4 hypertensive retinopathy was present in 9.8% patients for which association between the groups was significant. Acute infarct was present in 19.5% patients, chronic infarct was present in 9.8% patients, acute haemorrhagic stroke was present in 17.1% patients and chronic haemorrhagic stroke was present in 9.8% patients association between the groups was found to be statistically significant. Isolated systolic dysfunction was present in 2.4% patients, isolated diastolic dysfunction was present in 36.6% patients and both systolic and diastolic dysfunction was present in 4.9% patients association between the groups was found to be statistically significant.Conclusion: According to the study, increased albumin excretion rate may be a useful marker of arterial damage and a risk predictor of premature cardiovascular morbidity and death in hypertensive persons