Practice and short-term outcomes in ventral hernia repair: a prospective multicenter data audit of Indian Association of Gastrointestinal Endo Surgeons Research Collaborative.

INTRODUCTION: There is considerable variation in the practice of ventral hernia repair (VHR). Consequently, both short- and long-term outcomes are different. We report the first multicenter data from India on the variations in procedures and short-term outcomes after ventral hernia repair. METHODS: A prospective study was planned under the aegis of the Indian Association of Gastrointestinal Endo Surgeons (IAGES). Participating surgeons prospectively recorded the data of patients who underwent VHR from January 21, 2021, to April 20, 2021. Patients were followed for 3-6 months. RESULTS: Data from 648 patients were analyzed for demographics, hernia characteristics, technical variations, and outcomes. 375 (57.8%) were primary hernias (PH) and 273 (42.15%) were incisional hernias (IH), of which 63 (9.7%) were recurrent hernias. In the PH group, there were 171 minimal access (MAS) and 170 open repair. In descending order of frequency, there were 111 (32.6%) open onlay, 83 (24.3%) intraperitoneal onlay meshplasty (IPOM) Plus, 36 (10.6%) IPOM, 35 (10.3%) suture repair, 22 (6.5%) endoscopic Rives Stoppa (eRS), 11 (3.2%) open RS, 11 (3.2%) TAPP, 7 (2%) hybrid, 6 (1.8%) open preperitoneal, 19 (5.6%) others. There were 3.73% seroma, 3.2% SSI, 0% 90-day readmission, 0% recurrence, and 0.3% mortality. In the IH group, 164 patients underwent open repair and 104 MAS repair. In descending order of frequency, there were 90 (33.6%) open onlay, 47 (17.5%) IPOM Plus, 38 (14.1%) open sublay, 28 (10.4%) IPOM, 12 (4.5%) Transversus Abdominis Release (TAR), 11 (4.1%) suture repair, 9 (3.4%) open preperitoneal, 7 (2.6%) hybrid, 6 (2.2%) TAPP, 5 (1.9%) eRS, 4 (1.5%) TARM, 3 (1.1%) endoscopic TAR (eTAR), and 8 (3%) others. There were 13.92% seroma, 4.4% hematoma, 9.5% SSI, 1.1% mesh explantation, 0.4% wound sinus, 2.2% 90-day readmission, 0% recurrence, and 1.1% mortality. CONCLUSION: Onlay meshplasty is the commonest procedure in India both in PH and IH. IPOM/IPOM plus is the second commonest procedure. TAR is the preferred component separation technique. Complication rates were comparable to published literature. TRIAL REGISTRATION: The study was registered with Clinical Trial Registry of India. CTRI number-CTRI/2021/01/030435.

A de novo paradigm for male infertility.

De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10-5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10-4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.

A literature review of consent declines and consent withdrawals in randomized controlled trials conducted during the COVID-19 pandemic.

Objectives: We evaluated the extent of consent declines and consent withdrawals during the COVID-19 pandemic as seen in published randomized controlled trials (RCTs) and compared it with non-COVID-19 RCTs published at the same time and two historical controls. Methods: PubMed/Medline only was searched using key-word "COVID-19" and "RCTs" separately, and filtered for COVID-19 RCTs and non-COVID-19 RCTs respectively, published during a nine-month period (1 Feb - 1 Nov 2020). Exclusions were study protocols, observational studies, interim analysis of RCT data and RCTs with missing data. Primary outcome measures were the proportion of consent declines and consent withdrawals as percentage of total participants screened and randomized respectively in COVID-19 RCTs. We compared consent declines and consent withdrawals of COVID-19 RCTs with non-COVID-19 RCTs and two earlier studies on the same topic that served as historical controls (non-pandemic setting). Results: The search yielded a total of 111 COVID-19 RCTs and 49 non-COVID-19 RCTs. Of these, 39 (35.13%) COVID-19 RCTs and 11 (22.45%) non-COVID-19 RCTs were finally analysed. A total of 770/17759 (4.3%) consent declines and 100/7607 (1.31%) consent withdrawals were seen in 39 COVID-19 RCTs. A significant difference was observed in consent declines between COVID-19 vs non-COVID-19 RCTs [4.3% vs 11.9%, p < 0.0001] and between COVID-19 RCTs vs two historical controls [(4.3% vs 8.6%, p < 0.0001) and (4.3% vs 21.1%, p < 0.0001), respectively]. Conclusion: RCTs conducted during the COVID-19 pandemic appear to have significantly lower consent declines relative to non-COVID-19 RCTs during pandemic and RCTs conducted in non-pandemic settings.

Exome sequencing reveals variants in known and novel candidate genes for severe sperm motility disorders.

STUDY QUESTION: What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders? SUMMARY ANSWER: We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 10 out of 21 patients (48%) and variants in novel candidate genes in seven additional patients (33%). WHAT IS KNOWN ALREADY: Severe sperm motility disorders are a form of male infertility characterised by immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum that do not affect viability. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 22 genes. STUDY DESIGN, SIZE, DURATION: We performed exome sequencing in 21 patients with severe sperm motility disorders from two different clinics. PARTICIPANTS/MATERIALS, SETTING, METHOD: Two groups of infertile men, one from Argentina (n = 9) and one from Australia (n = 12), with clinically defined severe sperm motility disorders (motility <5%) and normal morphology values of 0-4%, were included. All patients in the Argentine cohort were diagnosed with DFS-MMAF, based on light and transmission electron microscopy. Sperm ultrastructural information was not available for the Australian cohort. Exome sequencing was performed in all 21 patients and variants with an allele frequency of <1% in the gnomAD population were prioritised and interpreted. MAIN RESULTS AND ROLE OF CHANCE: In 10 of 21 patients (48%), we identified pathogenic variants in known sperm assembly genes: CFAP43 (3 patients); CFAP44 (2 patients), CFAP58 (1 patient), QRICH2 (2 patients), DNAH1 (1 patient) and DNAH6 (1 patient). The diagnostic rate did not differ markedly between the Argentinian and the Australian cohort (55% and 42%, respectively). Furthermore, we identified patients with variants in the novel human candidate sperm motility genes: DNAH12, DRC1, MDC1, PACRG, SSPL2C and TPTE2. One patient presented with variants in four candidate genes and it remains unclear which variants were responsible for the severe sperm motility defect in this patient. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, we described patients with either a homozygous or two heterozygous candidate pathogenic variants in genes linked to sperm motility disorders. Due to unavailability of parental DNA, we have not assessed the frequency of de novo or maternally inherited dominant variants and could not determine the parental origin of the mutations to establish in all cases that the mutations are present on both alleles. WIDER IMPLICATIONS OF THE FINDINGS: Our results confirm the likely causal role of variants in six known genes for sperm motility and we demonstrate that exome sequencing is an effective method to diagnose patients with severe sperm motility disorders (10/21 diagnosed; 48%). Furthermore, our analysis revealed six novel candidate genes for severe sperm motility disorders. Genome-wide sequencing of additional patient cohorts and re-analysis of exome data of currently unsolved cases may reveal additional variants in these novel candidate genes. STUDY FUNDING/COMPETING INTEREST(S): This project was supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., J.A.V. and R.I.M.L., The Netherlands Organisation for Scientific Research (918-15-667) to J.A.V., the Royal Society and Wolfson Foundation (WM160091) to J.A.V., as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. and Grants from the National Research Council of Argentina (PIP 0900 and 4584) and ANPCyT (PICT 9591) to H.E.C. and a UUKi Rutherford Fund Fellowship awarded to B.J.H.

Congenital intestinal malrotation presenting in octogenarians: a report of two cases.

Malrotation is part of a spectrum of small and large bowel positional and fixational abnormalities caused by the failure of the fetal intestine to complete a 270-degree rotation around the superior mesenteric artery axis. Rarely, it presents in the adult as a cause of acute small bowel obstruction. Chronic symptoms of malrotation in adults are subtle, and include intermittent abdominal pain, nausea and vomiting. We present two cases of malrotation in octogenarian men presenting acutely with small bowel obstruction. Both patients were treated with emergency surgery. In one case the chronic symptoms resolved postoperatively. Malrotation and midgut volvulus should be considered as a rare differential diagnosis for small bowel obstruction in adults. Suspicions should be increased when there is a history of recurrent presentations with similar symptoms.

Diagnostic dilemma of gastric intramural air.

Emphysematous gastritis and gastric emphysema remain the two most important differential diagnoses of intramural gastric air bubbles, both differing vastly in their clinical presentation, radiographic findings, management and prognosis. This report discusses a case of gastric emphysema along with the importance of reaching an accurate clinical diagnosis early in the disease course.

Diffusional kurtosis imaging of the developing brain.

BACKGROUND AND PURPOSE: Diffusional kurtosis imaging is an extension of DTI but includes non-Gaussian diffusion effects, allowing more comprehensive characterization of microstructural changes during brain development. Our purpose was to use diffusional kurtosis imaging to measure age-related microstructural changes in both the WM and GM of the developing human brain. MATERIALS AND METHODS: Diffusional kurtosis imaging was performed in 59 subjects ranging from birth to 4 years 7 months of age. Diffusion metrics, fractional anisotropy, and mean kurtosis were collected from VOIs within multiple WM and GM structures and subsequently analyzed with respect to age. Diffusional kurtosis tractography images at various stages of development were also generated. RESULTS: Fractional anisotropy and mean kurtosis both showed age-related increases in all WM regions, reflecting progression of diffusional anisotropy throughout development, predominantly in the first 2 years of life (eg, 70% and 157% increase in fractional anisotropy and mean kurtosis, respectively, from birth to 2 years for the splenium). However, mean kurtosis detected continued microstructural changes in WM past the fractional anisotropy plateau, accounting for more delayed isotropic changes (eg, 90% of maximum fractional anisotropy was reached at 5 months, whereas 90% of maximum mean kurtosis occurred at 18 months for the external capsule). Mean kurtosis may also provide greater characterization of GM maturation (eg, the putamen showed no change in fractional anisotropy but an 81% change in mean kurtosis from birth to 4 years 7 months). CONCLUSIONS: Mean kurtosis detects significant microstructural changes consistent with known patterns of brain maturation. In comparison with fractional anisotropy, mean kurtosis may offer a more comprehensive evaluation of age-related microstructural changes in both WM and GM and is potentially a valuable technique for studying brain development.

Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Development of full-thickness macular hole despite previous posterior vitreous detachment and vitrectomy for retinal detachment: two cases.

PURPOSE: To report the delayed development of idiopathic full-thickness macular hole in eyes with previously documented complete posterior vitreous detachment that were vitrectomized during surgery for rhegmatogenous retinal detachment. METHODS: Two interventional case reports with serial color fundus photographs and optical coherence tomography scans. RESULTS: Case 1: A 62-year-old man underwent vitrectomy, cryoretinopexy, and intraocular gas tamponade for rhegmatogenous retinal detachment associated with a complete posterior vitreous detachment. Three years later, he developed a full-thickness macular hole in the same eye. Peeling of the inner limiting membrane and gas tamponade resulted in complete closure of the macular hole with improvement in visual acuity. Case 2: A 70-year-old man presented with a macula-off inferior retinal detachment and counting fingers vision. Vitrectomy, cryoretinopexy to a single tear, and gas tamponade was successful and acuity improved to 6/9. He subsequently developed retinal redetachment associated with a new retinal tear and was treated by further vitrectomy and gas. He developed a full-thickness macular hole in the same eye 2 years later with acuity dropping to 1/60. CONCLUSIONS: Macular hole formation may occur in the context of vitrectomized eyes. These observations support the hypothesis that anteroposterior vitreomacular traction, while traditionally implicated, is not always essential for the development of macular holes.

Punctate inner choroidopathy-associated choroidal neovascular membranes during pregnancy.

UNLABELLED: PURPOSE AND MATERIALS: Punctate inner choroidopathy (PIC), first described by Watzke et al(1), is a disease in young women of child-bearing age. We present three cases of PIC-associated choroidal neovascular membrane (CNVM) occurring during pregnancy, and discuss associated investigative and treatment dilemmas. RESULTS: All three patients described showed evidence of recurrence of CNVM during their pregnancy. None underwent FFA but benefited from OCT monitoring. Different therapeutic strategies were adopted in each of our cases. Case 1, with a history of spontaneous CNVM regression, was managed conservatively. Cases 2 and 3 chose steroid treatment to their better-seeing eye. All cases remained stable postpartum. DISCUSSION: Management of PIC-related CNVM creates diagnostic and therapeutic challenges. The problem is exacerbated as the pathology is often sequentially bilateral and sight threatening. Owing to the rarity of such cases, there is a paucity of evidence on which to base the treatment strategies. A history of pregnancy should always be elicited before investigation with FFA, and women warned of the potential for disease exacerbation with limited therapeutic options during pregnancy. CONCLUSIONS: spontaneous resolution of CNVM is common in PIC, and should be borne in mind while treating pregnant women. Peri/intraocular steroid injection represents a reasonable option for sight-threatening CNVM in the better-seeing eye.

A prospective study of change in visual function in patients treated with pegylated interferon alpha for hepatitis C in the UK.

BACKGROUND: Hepatitis C virus and interferon treatment have been associated with retinopathy. Baseline and ongoing assessment by ophthalmologists have therefore been advocated in previous studies. Our experience suggests that the incidence is low, with no or negligible impact of pegylated interferon alpha on actual visual function. This study was conducted to determine whether ophthalmic assessment is necessary in such patients. METHODS: The study was a prospective case series of 52 patients (104 eyes). Visual acuity, contrast sensitivity, colour vision, visual field by perimetry and fundal assessment were measured at baseline and at 3 and 6 months post commencement of interferon alpha treatment. RESULTS: Forty-two men and ten women were followed. No patients reported any subjective visual symptoms. The mean changes in right and left logarithmic minimal angle resolution (LogMAR) visual acuity were negligible between baseline and 6 months (0.05 (SD 0.13) and 0.10 (SD 0.12), respectively). Mean changes in contrast sensitivity and colour vision were also negligible. Of all eyes monitored by serial perimetry for the full follow-up period and deemed to have reliable tests, none developed visual field defects. One patient appeared to develop nasal field defects within 3 months of commencing treatment but failed to attend for repeat testing. No patients developed optic disc changes or permanent fundal changes over the follow-up period. CONCLUSION: In contrast to previous studies in America and south-east Asia, our findings based on a UK cohort suggest that routine ophthalmic screening is not essential for patients with hepatitis C treated with pegylated interferon alpha who have no subjective visual complaints.

Patient consultation survey in an ophthalmic outpatient department.

INTRODUCTION: Consultation methods differ between medical practitioners depending on the individual setting. However, the central tenet to the doctor-patient relationship is the issue of confidentiality. This prospective survey highlights patient attitudes towards consultation methods in the setting of an ophthalmic outpatient department. METHOD: Questionnaires were completed by 100 consecutive patients, who had been seen by an ophthalmologist in a single room, which had a joint doctor-patient consultation occurring simultaneously. RESULTS: Each question of all 100 questionnaires was completed. 58% of patients were not concerned about sharing a consultation room with another patient or doctor. However, this did not equate to the 49% of patients who were indifferent to discussing issues in the joint consultation room. The most common factor was the general issue of confidentiality. DISCUSSION: Ensuring total patient confidentiality may be deemed more necessary for certain medical specialties than for others, as seen in the practice of separate medical records in genitourinary medicine, for instance. However, with regard to patient consultations, the same level of confidentiality should be afforded across all specialties, and such factors should be borne in mind when planning outpatient clinics.

Emergency management of corneal injuries.

UNLABELLED: Corneal injuries account for a significant proportion of the ophthalmic workload of most emergency departments. Although the vast majority of cases are relatively minor, accurate diagnosis and appropriate management are vital to prevent potentially sight-threatening sequelae. We present a survey of corneal injury cases at a general emergency department. INTRODUCTION: Corneal injuries are very common in both the adult and paediatric population and account for a significant proportion of the workload of most emergency departments. This survey assesses management of corneal injury cases at a general emergency department. MATERIALS AND METHODS: A retrospective case study was performed of 100 patients consecutively diagnosed with a corneal abrasion by slit lamp examination at the emergency department of the Chelsea and Westminster Hospital, London. Each case was assessed to determine documentation of set criteria including visual acuity (VA), treatment and grade of examiner. RESULTS: The commonest cause of injury was direct minor trauma (64% of cases) with contact lens related problems accounting for 12% of presentations. VA was documented correctly in 85 adult patients (90.4% of adults), incorrectly in 2 cases, and not documented at all in 7 adults (7.4%). VA was not recorded in paediatric cases. All cases were treated with topical chloramphenicol drops although frequency of treatment ranged from 2 to 5 times daily and duration of treatment ranged between 3 and 5 days and for 7 days. 6 cases (6%) were assessed by an emergency nurse practitioner and the remaining number were seen by a casualty officer. DISCUSSION: VA must be accurately documented in all adult cases and should be documented in children of school age. A pinhole test should be performed in cases where VA is below 6/9. For analgesia, the use of topical nonsteroidal anti-inflammatory drugs, lubricants and bandage contact lens should be considered. Emergency nurse practitioners and general practitioners are ideally placed to follow-up uncomplicated cases.

UK national survey of prophylactic YAG iridotomy.

PURPOSE: Acute angle-closure glaucoma is a common ophthalmic emergency and individuals with shallow anterior chambers and suspected narrow angles are increasingly referred to the hospital eye service for assessment. There appears to be variation in subsequent management, with no national consensus or college guidelines. This study ascertains the current use of prophylactic YAG iridotomy in patients with no known history of an acute angle-closure glaucoma attack, and also the methods used in patient selection. MATERIALS AND METHODS: Questionnaire-based survey mailed to 650 UK consultant ophthalmologists with a covering letter in 2003. RESULTS: A total of 546 questionnaires were returned. In all, 408 respondents (74.7%) confirmed they perform prophylactic YAG iridotomy and of these 347 (85.0%) use patient symptoms and 268 (65.6%) presenting IOP in patient selection, 394 (96.6%) perform gonioscopy and 97 (23.8%) use some form of provocative test first. A total of 135 (25.3%) stated they do not perform this procedure. CONCLUSION: This study reveals current national practice among UK ophthalmologists, with variations in the assessment of patients with narrow angles but a high uptake of prophylactic YAG iridotomy.