Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients.

BACKGROUND: Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. METHODS: This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. RESULTS: Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (ß = -0.28, p = 0.01) but had no effect on depression severity at follow-up (ß = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (ß = 0.81, p < 0.001; and ß = 0.31, p = 0.001, respectively). CONCLUSIONS: Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.

Role of Ursodeoxycholic Acid in the Prevention of Gallstones Formation in Bariatric Patients-a Systematic Review and Meta-Analysis of Randomised Trials.

The aim of this meta-analysis was to assess whether treatment with ursodeoxycholic acid (UDCA) in patients who have undergone bariatric surgery reduces gallstone formation. A systematic literature search was performed using electronic databases (MEDLINE, Embase, CENTRAL, Web of Science, PROSPERO, Google Scholar and the WHO International Clinical Trials Registry platform). RCTs without restrictions on study language, year, status of publication and patient's age were used. Pooled risk ratios were calculated using a random-effects model. Subgroup analyses for drug dose, duration and procedure types were performed. Sensitivity analyses and a summary of findings table were generated to assess the robustness and the level of evidence provided, respectively. Fourteen trials were included (3619 patients, 2292 in UDCA vs 1327 in control group). Procedures included SG, RYGB, OAGB, AGB and Gastroplasty. UDCA dose ranged from 300 to 1200 mg per day. Gallstone formation occurred in 19.3% (8.3% in UDCA vs 38.1% in the control group). UDCA significantly reduced the risk of gallstone formation (14 trials, 3619 patients; RR 0.27, 95% CI 0.18-0.41; P < 0.001). UDCA significantly reduced the risk of symptomatic gallstone disease (6 trials, 2458 patients; RR 0.30, 95% CI 0.21-0.43; P < 0.001). No subgroup difference was found for different doses, duration and type of procedure performed. Oral UDCA treatment significantly reduces the risks of developing gallstones in postoperative bariatric patients from 38 to 8%. The use of 500 to 600 mg UDCA for 6 months is effective and should be implemented in all patients post-bariatric surgery.

Second-line treatment with CAR T-cell therapy for large B-cell lymphoma.

The landscape for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) has continued to evolve. However, challenges continue to exist, particularly in patients who do not respond to first-line anti-CD20 monoclonal antibody and anthracycline-based therapy or those who experience early relapse. In such patients, the treatment paradigm has changed little in the past 2 decades, with salvage chemotherapy followed by myeloablative chemotherapy and autologous hematopoietic stem cell transplant resulting in historical durable response rates of approximately 40%. Given the success of chimeric antigen receptor (CAR) T-cell therapy in the third- or later-line in the R/R LBCL setting, 3 recent clinical trials (ZUMA-7, BELINDA, and TRANSFORM) have sought to address the clinical need for improved therapies in the high-risk second-line setting for primary R/R disease in the first 12 months. In this review, we analyze these 3 pivotal trials with a focus on clinical trial design, CAR T-cell product attributes, efficacy data, safety data, and patient-reported outcomes when compared with standard of care.

Patient-specific comorbidities as prognostic variables for survival in myelofibrosis.

Treatment decisions in primary myelofibrosis (PMF) are guided by numerous prognostic systems. Patient-specific comorbidities have influence on treatment-related survival and are considered in clinical contexts but have not been routinely incorporated into current prognostic models. We hypothesized that patient-specific comorbidities would inform prognosis and could be incorporated into a quantitative score. All patients with PMF or secondary myelofibrosis with available DNA and comprehensive electronic health record (EHR) data treated at Vanderbilt University Medical Center between 1995 and 2016 were identified within Vanderbilt's Synthetic Derivative and BioVU Biobank. We recapitulated established PMF risk scores (eg, Dynamic International Prognostic Scoring System [DIPSS], DIPSS plus, Genetics-Based Prognostic Scoring System, Mutation-Enhanced International Prognostic Scoring System 70+) and comorbidities through EHR chart extraction and next-generation sequencing on biobanked peripheral blood DNA. The impact of comorbidities was assessed via DIPSS-adjusted overall survival using Bonferroni correction. Comorbidities associated with inferior survival include renal failure/dysfunction (hazard ratio [HR], 4.3; 95% confidence interval [95% CI], 2.1-8.9; P = .0001), intracranial hemorrhage (HR, 28.7; 95% CI, 7.0-116.8; P = 2.83e-06), invasive fungal infection (HR, 41.2; 95% CI, 7.2-235.2; P = 2.90e-05), and chronic encephalopathy (HR, 15.1; 95% CI, 3.8-59.4; P = .0001). The extended DIPSS model including all 4 significant comorbidities showed a significantly higher discriminating power (C-index 0.81; 95% CI, 0.78-0.84) than the original DIPSS model (C-index 0.73; 95% CI, 0.70-0.77). In summary, we repurposed an institutional biobank to identify and risk-classify an uncommon hematologic malignancy by established (eg, DIPSS) and other clinical and pathologic factors (eg, comorbidities) in an unbiased fashion. The inclusion of comorbidities into risk evaluation may augment prognostic capability of future genetics-based scoring systems.

Parkinson's Disease Diagnosis beyond Clinical Features: A Bio-marker using Topological Machine Learning of Resting-state Functional Magnetic Resonance Imaging.

Parkinson's disease (PD) is one of the leading causes of neurological disability, and its prevalence is expected to increase rapidly in the following few decades. PD diagnosis heavily depends on clinical features using the patient's symptoms. Therefore, an accurate, robust, and non-invasive bio-marker is of critical clinical importance for PD. This study proposes to develop a new bio-marker for PD diagnosis using resting-state functional Magnetic Resonance Imaging (rs-fMRI). Unlike most existing rs-fMRI data analytics using correlational analysis, a Topological Machine Learning approach is proposed to construct the bio-marker. The default functional network is identified first using rs-fMRI. Next, rs-fMRI's high dimensional spatial-temporal data structure is mapped on a Riemann Manifold using topological dimensional reduction. Following the topological dimensional reduction, machine learning is used for classification and sensitivity analysis. The proposed methodology is applied to three open fMRI databases for demonstration and validation. The PD diagnosis accuracy can reach 96.4% when the proposed methodology is used. Thus, rs-fMRI and topological machine learning provide a quantifiable and verifiable bio-marker for future PD early detection and treatment evaluation.

The efficacy of GLP-1RAs for the management of postprandial hypoglycemia following bariatric surgery: a systematic review.

OBJECTIVE: Postprandial hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly recognized complication of Roux-en-Y gastric bypass and gastric sleeve surgery that may detrimentally affect patient quality of life. One likely causal factor is glucagon-like peptide-1 (GLP-1), which has an exaggerated rise following ingestion of carbohydrates after bariatric surgery. This paper sought to assess the role of GLP-1 receptor agonists (GLP-1RAs) in managing postprandial hypoglycemia following bariatric surgery. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus were systematically and critically appraised for all peer-reviewed publications that suitably fulfilled the inclusion criteria established a priori. This systematic review was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P). It followed methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and is registered with PROSPERO (International Prospective Register of Systematic Reviews; identifier CRD420212716429). RESULTS AND CONCLUSIONS: Postprandial hyperinsulinemic hypoglycemia remains a notoriously difficult to manage metabolic complication of bariatric surgery. This first, to the authors' knowledge, systematic review presents evidence suggesting that use of GLP-1RAs does not lead to an increase of hypoglycemic episodes, and, although this approach may appear counterintuitive, the findings suggest that GLP-1RAs could reduce the number of postprandial hypoglycemic episodes and improve glycemic variability.

Novel JAK2 Exon 14 Mutations L611S or N622Y in cis with JAK2V617F Are Associated with Distinct Clinical Phenotype of Polycythemia Vera and Concurrent Eosinophilia.

Eosinophilic phenotypes in polycythemia vera (PV) and essential thrombocythemia (ET) are rare and poorly characterized. Co-occurring JAK2 mutations in cis, specifically L611S or N622Y mutations, appear to result in a more aggressive clinical phenotype. PV/ET with eosinophilic phenotypes may require full next-generation sequencing to capture co-occurring mutations as opposed to more prevalent single-gene assays. These eosinophilic phenotypes are highly thrombotic and systemic symptoms appear responsive to early use of the janus kinase inhibitor ruxolitinib.

Successful endoscopic management of Bouveret syndrome.

We present a frail 83-year-old female with Bouveret syndrome managed using an endoscopic approach. Our patient attended the emergency department with abdominal pain, vomiting and signs of sepsis. She had a recent admission with acute cholecystitis that which had been managed conservatively. Axial imaging revealed aerobilia with a 14 mm common bile duct and a 3.5 cm calculus impacted in the duodenum, in association with a cholecysto-duodenal fistula. After resuscitation, an oesphagoduodenoscopy was performed under general anaesthesia. The large stone was seen impacted in the first part of duodenum. Mechanical lithotripsy and the Kudo snare were employed to fragment the stone and remove large fragments. Bouveret syndrome is rarely managed with success through endoscopy. The syndrome typically occurs in frail, elderly co-morbid patients who would benefit from endoscopic management over open surgery. Despite low success rates historically, endoscopic management is a reasonable and viable option in cases of Bouveret syndrome.

Effect of the learning curve on survival after laparoscopic liver resection for colorectal metastases.

BACKGROUND: Laparoscopic liver resection (LLR) is a highly demanding procedure with great variability. Previously published randomized trials have proven oncological safety of laparoscopic liver resection (LLR) as compared to open surgery. However, these were started after the learning curve (LC) was established. This leaves the question of whether the LC of LLR in the early laparoscopic era has affected the survival of patients with colorectal liver metastasis (CRLM). METHODS: All consecutive LLRs performed by a single surgeon between 2000 and 2019 were retrospectively analysed. A risk-adjusted cumulative sum (RA-CUSUM) chart for conversion rate and the log regression analysis of the blood loss identified two phases in the LC. This was then applied to patients with CRLM, and the two subgroups were compared for recurrence-free (RFS) and overall survival (OS). The analysis was repeated with propensity score-matched (PSM) groups. RESULTS: A total of 286 patients were included in the LC analysis, which identified two distinct phases, the early (EP; 68 patients) and the late (LP; 218 patients) phases. The LC was applied to 192 patients with colorectal liver metastasis (EPc, 45 patients; LPc, 147 patients). For patients with CRLM, R0 resection was achieved in 93 per cent: 100 per cent in the EPc group and 90 per cent in the LPc group (P = 0.026). Median OS and RFS were 60 and 16 months, respectively. The 5-year OS and RFS were 51 per cent and 32.7 per cent, respectively. OS (hazard ratio (h.r.) 0.78, 95 per cent confidence interval (c.i.) 0.51 to 1.2; P = 0.286) and RFS (h.r. 0.94, 95 per cent c.i. 0.64 to 1.37; P = 0.760) were not compromised by the learning curve. The results were replicated after PSM. CONCLUSION: In our experience, the development of a laparoscopic liver resection programme can be achieved without adverse effects on the long-term survival of patients with CRLM.

Liver abscess secondary to fishbone ingestion: case report and review of the literature.

We report a rare silent migration of a fishbone into the liver and review the relevant literature. A 56-year-old man presented with a 2-day history of dull epigastric pain and raised inflammatory markers. Computerized tomography scan revealed a 4-cm abscess in the left lobe of the liver, with a linear radio-dense foreign body within the collection. At laparoscopy the hepatogastric fistula was disconnected. The fishbone was retrieved from the liver. Gastrostomy was closed with an omental patch. The patient had an uneventful recovery. Fifty-two cases of liver abscess secondary to enterohepatic fishbone migration were reported with over two-thirds presenting with a left-lobe abscess. There was marked variability in the management of liver abscess in the setting of fishbone migration-summarized in table. We believe that laparoscopic drainage of the abscess and extraction of the foreign body offer control of the source of sepsis and diminishes recurrence, whilst having a low-risk profile.

Reduction in the Prevalence of Thrombotic Events in Sickle Cell Disease after Allogeneic Hematopoietic Transplantation.

Thrombosis is a recognized complication in sickle cell disease (SCD). Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for patients with severe SCD phenotypes. Data describing the effects of allo-HCT on recurrent thrombotic events (venous and arterial events) are limited, however. We evaluated 31 patients with SCD who underwent allo-HCT with a median follow-up of 34.5 months (range, 13 to 115) post-transplantation. No patient continued anticoagulation or antiplatelet therapy after allo-HCT. There was an absolute difference of 32% (95% confidence interval [CI], 12.3% to 32.2%; P = .002) in the prevalence of venous thromboembolic (VTE) events before and after allo-HSCT. In addition, there was an absolute difference of 38.5% (95% CI, 10.63 to 45.96; P = .006) in the number of ischemic cerebrovascular accidents (CVAs) occurring before and after allo-HSCT. Patients with severe SCD who undergo allo-HCT are less likely to develop recurrent thrombotic events compared with a control cohort of patients matched for age and genotype (odds ratio, 0.22; 95% CI, 0.058 to 0.83; P = .025). Following curative therapy with allo-HCT, there is a reduction in recurrent arterial and venous thrombosis in patients with severe SCD phenotypes.

High Sensitivity Troponin T and NT-proBNP in Patients Receiving Chimeric Antigen Receptor (CAR) T-Cell Therapy.

Retrospective studies suggest that chimeric antigen receptor T-cell (CAR T) therapy may lead to cardiac injury, but this has not been assessed systematically or prospectively. In this prospective study of 40 patients who received CAR T, we systematically measured high-sensitivity troponin T (hsTropT) and N-terminal pro-B natriuretic peptide (NTproBNP) at baseline and on day 1, days 7, and 21 after CAR T. Biomarker elevations with respect to timepoint and cytokine release syndrome (CRS) status were examined using repeated measure analysis of variance. hsTropT did not differ with time or with the presence of grade 2 CRS. Median hsTropT was 12.1 ng/L [interquartile range (IQR): 9.2, 20.1] at baseline, 13.1 ng/L (IQR: 9.6, 24.2) at day 1, 11.9 ng/L (IQR: 9.6, 18.0) at day 7, and 15.3 ng/L (10.8, 20.2) at day 21. In contrast, NTproBNP rose on day 1 (P Wilcox = 0.0002) and day 7 (P Wilcox = 2.7 × 10-5), and the degree of elevation differed by the presence of grade 2 CRS (P interaction = 0.002). Median NTproBNP was 179 pg/mL (IQR: 116, 325) at baseline, 357 pg/mL (IQR: 98, 813) at day 1, 420 pg/mL (IQR: 239, 1242) at day 7, and 177 pg/mL (IQR: 80, 278) at day 21. In conclusion, hsTropT l did not differ across timepoints after CAR T therapy, but NTproBNP rose at day 7, the prognostic implications of which should be the target of future research, as the indications for this therapy expand.

Taking a BiTE out of the CAR T space race.

Chimaeric antigen receptor T-cell (CAR T) therapy has evolved at an exponential pace and seeks to revolutionize the CAR T space with next-generation CARs and expanding indications in plasma cell dyscrasias. Recent developments in Bispecific T-cell engager therapy (BiTEs) may level the playing field with CAR T therapy, offering key advantages with off-the-shelf or on-demand treatment and a manageable toxicity profile to encompass a wider pool of eligible patients in the outpatient setting. The coexistence of both modalities will remain important in overall management and accelerate the next iteration of both cellular and BiTEs. This article summarises the current progress, potential future of both therapies for haematologic malignancies, and their economic implications on the healthcare system.

Weight loss with bariatric surgery or behaviour modification and the impact on female obesity-related urine incontinence: A comprehensive systematic review and meta-analysis.

Women with obesity are at risk of pelvic floor dysfunction with a 3-fold increased incidence of urge urinary incontinence (UUI) and double the risk of stress urinary incontinence (SUI). The National Institute for Health and Care Excellence (NICE) and European Association of Urology (EAU) recommend that women with a body mass index ≥30 kg/m2 should consider weight loss prior to consideration for incontinence surgery. This systematic review and meta-analysis will assess this recommendation to aid in the counselling of women with obesity-related urinary incontinence (UI). Medical Literature Analysis and Retrieval System online (MEDLINE), EMBASE, Cochrane, ClinicalTrials.gov, and SCOPUS were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori and presented original, empirical data relevant to weight loss intervention in the management of urinary incontinence. Thirty-three studies and their outcomes were meta-analysed. Weight loss interventions were associated in a decreased prevalence in UI (OR 0.222, 95% CI [0.147, 0.336]), SUI (OR 0.354, 95% CI [0.256, 0.489]), UUI (OR 0.437, 95% CI [0.295, 0.649]) and improved quality of life (PFDI-20, SMD -0.774 (95% CI [-1.236, -0.312]). This systematic review and meta-analysis provide evidence that weight loss interventions are effective in reducing the prevalence of obesity-related UI symptoms in women. Bariatric surgery in particular shows greater sustained weight loss and improvements in UI prevalence. Further large scale, randomized control trials assessing the effect of bariatric surgery on women with obesity-related UI are needed to confirm this study's findings.

The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass. RESEARCH DESIGN AND METHODS: A total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery. RESULTS: Both groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. CONCLUSIONS: The findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

Deep neural network to locate and segment brain tumors outperformed the expert technicians who created the training data.

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively ( p < 0.00007 ). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its "human teachers" and produced output that was better, on average, than its training data.

Multiple reader comparison of 2D TOF, 3D TOF, and CEMRA in screening of the carotid bifurcations: Time to reconsider routine contrast use?

BACKGROUND AND PURPOSE: MR contrast-enhanced techniques are undergoing increased scrutiny since the FDA applied a warning for gadolinium-based MR contrast agents due to gadolinium deposition within multiple organ systems. While CE-MRA provides excellent image quality, is it required in a screening carotid study? This study compares 2D TOF and 3D TOF MRA vs. CE-MRA in defining carotid stenosis in a large clinical patient population, and with multiple readers with varying experience. MATERIALS AND METHODS: 200 consecutive patients had their carotid bifurcations evaluated with 2D TOF, 3D TOF and CE-MRA sequences by 6 board-certified neuroradiologists. Stenosis and quality of examinations were defined for each study. Inter-rater reliability was assessed using two-way random effects intraclass correlation coefficients. Intra-reader reliability was computed via weighted Cohen's κ. Weighted Cohen's κ were also computed to assess agreement in stenosis ratings between enhanced images and unenhanced images. RESULTS: Agreement between unenhanced and enhanced ratings was substantial with a pooled weighted κ of 0.733 (0.628-0.811). For 5 of the 6 readers, the combination of unenhanced 2D TOF and 3D TOF showed better agreement with contrast-enhanced than either 2D TOF or 3D TOF alone. Intra-reader reliability was substantial. CONCLUSIONS: The combination of 2D TOF and 3D TOF MRA showed substantial agreement with CE-MRA regarding degree of carotid stenosis in this large outpatient population across multiple readers of varying experience. Given the scrutiny that GBCA are undergoing due to concerns regarding CNS and soft tissue deposition, it seems prudent to reserve CE-MRA for cases which are not satisfactorily answered by the nonenhanced study or other noninvasive examinations.

Male Obesity Associated Gonadal Dysfunction and the Role of Bariatric Surgery.

Obesity is an ever growing pandemic and a prevalent problem among men of reproductive age that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the precision and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and preclinical data support these findings. Clinical studies on the impact of medically induced weight loss on serum testosterone concentrations and spermatogenesis is promising but may show differential and unsustainable results. In contrast, literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in serum testosterone concentrations that is superior than that obtained with only lifestyle modifications, supporting a further metabolic benefit from surgery that may be specific to the male reproductive system. The data on sperm and semen parameters is controversial to date. Emerging evidence in the burgeoning field of genetics and epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, conveying the potential impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Healthcare professionals treating male infertility and obesity need to adapt their practice to assimilate these new findings to better counsel men about the importance of paternal preconception health and the impact of novel non-medical therapeutic interventions. Herein, we summarize the pathophysiology of obesity on the male reproductive system and emerging evidence regarding the potential role of bariatric surgery as treatment of male obesity-associated gonadal dysfunction.